Objectives: In this case report, we describe the design, fabrication and clinical outcomes of a novel bioresorbable, mineralized collagen burr-hole plug for the reconstruction of craniotomy burr-holes.
Methods: Mineralized collagen burr-hole plugs were fabricated via a biomimetic mineralization process. The biomimetic mineralized collagen has a similar chemical composition and microstructure to natural bone tissue, thereby possessing good biocompatibility and osteoconductivity. The mineralized collagen burr-hole plugs were implanted into three patients, and clinical outcomes were evaluated at one-year follow-ups.
Results: All bone defects healed very well using the mineralized collagen burr-hole plugs, and there were no adverse reactions at the surgical sites.
Conclusions: The clinical outcomes indicated that the mineralized collagen was effective for reconstructing burr-holes in the skull after craniotomy.

Objective: Parkinson's disease (PD), which is one of the most common neurodegenerative disorders, is characterized by the loss of dopamine (DA) neurons in the substantia nigra in the midbrain. Experimental and clinical studies have shown that fetal neural stem cells (NSCs) have therapeutic effects in neurological disorders. The aim of this study was to examine whether cells that were differentiated from NSCs had therapeutic effects in a rat model of PD. Methods: NSCs were isolated from 14-week-old embryos and induced to differentiate into neurons, DA neurons, and glial cells, and these cells were characterized by their expression of the following markers:βⅢ-tubulin and microtubule-associated protein 2 (neurons), tyrosine hydroxylase (DA neurons), and glial fibrillary acidic protein (glial cells). After a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD was generated, the differentiated cells were transplanted into the striata of the 6-OHDAlesioned PD rats. Results: The motor behaviors of the PD rats were assessed by the number of apomorphine-induced rotation turns. The results showed that the NSCs differentiated in vitro into neurons and DA neurons with high efficiencies. After transplantation into the striata of the PD rats, the differentiated cells significantly improved the motor deficits of the transplanted PD rats compared to those of the control nontransplanted PD rats by decreasing the apomorphine-induced turn cycles as early as 4 weeks after transplantation. Immunofluorescence analyses showed that the differentiated DA neurons survived more than 16 weeks. Conclusions: Our results showed that cells that were differentiated from NSCs had therapeutic effects in a rat PD model, which suggests that differentiated cells may be an effective treatment for patients with PD.

Objective: Taiwan has an increasing aging population like other developed areas. The aging population will lead to an increased prevalence of dementia. Methods: This article will reflect the status of dementia in Taiwan, including updated epidemiology, diagnosis, subtypes, and optimal treatment of dementia. Results: The article also describes and interprets the Taiwan Dementia Policy to establish a clear, large view of the current state of management of dementia in Taiwan and future policy implementation. Conclusion: A comprehensive policy to dementia, from the basic researches to clinical care and treatment, is necessary to the increased aged population in Taiwan.

The field of biomaterials has recently emerged to augment or replace lost or damaged tissues and organs due to the human body's limited ability to self-heal large defects. Historically, metallic components, polymers, ceramics, and composite materials were utilized as synthetic materials along with natural materials to assist in therapy. Various novel biomaterials were developed to respond to a significant amount of new medical challenges in the past decade. Therefore, there is a need to review these newly developed biomaterials and their potential to improve tissue repair and regeneration in a variety of applications. Here, we briefly review the different strategies and attempts to use novel biomaterials, including self-assembled and macromolecular biomaterials, hydrogels, metamaterials, decellularized tissues, and biomaterials obtained via synthetic biology, used either for tissue repair and regeneration or for therapeutic use by exploiting other mechanisms of healing. All these methods aim to create functional materials, devices, systems, and/or organisms with novel and useful functions on the basis of catalogued and standardized biological building blocks. This review details the various methods and introduces the applications of these biomaterials in tissue repair and regeneration, especially for bone, nerve, and skin applications.

Decompressive craniectomy (DC) is a surgical method for managing highly elevated intracranial increased pressure (ICP) resulted from severe head trauma. This procedure is able to reduce the ICP rapidly and effectively. However, it may lead to kinds of secondary complications, which would cause patient's severe neurological dysfunction or even death. In this paper, we reviewed the literatures about surgical complications secondary to DC, and tried to bring up suggestions on surgical techniques aiming to prevention and treatment of these complications.

Objective: The local regulations for conducting experimental and clinical cell therapy studies are dependent on the national and cultural approach to the issue, and may have many common aspects as well as differences with the regulations in other countries. The study reflects the latest national aspects of cell therapy in Iran and relevant regulations. Methods: The following topics are discussed in the article including sources of cell harvest, regulations for cell disposal, stem cell manufacturing, and economic aspects of stem cell, based on current practice in Iran. Results: All cell therapy trials in Iran are required to strictly abide with the ethical codes, national and local regulations, and safety requirements, as well as considering human rights and respect. Adherence to these standards has facilitated the conduct of human cell therapy trials for research, academic advancement, and therapy. Conclusions: The cell therapy trials based on the aforementioned regulations may be assumed to be ethical and they are candidates for clinical translations based on safety and efficacy issues.

Objective: Fibrous dysplasia (FD) is an unusual developmental abnormality of the skeleton. When facial and cranial bones are involved in FD, it is termed craniofacial fibrous dysplasia (CFD). Although several reports have reported that CFD has a tendency for spontaneous cerebrospinal fluid (CSF) leakage, there have been no related English-language case reports. We present the first case of post-traumatic CSF rhinorrhea associated with CFD. Methods: A 30-year-old man presented with CSF rhinorrhea after a mild head trauma. Computed tomography cisternogram located a defect in the posterior wall of the right frontal sinus. Imaging examination also showed the evident expansion of multiple skull bones, spinal scoliosis, and multiple local enlargements of ribs. Without café-au-lait cutaneous spots and endocrine abnormalities, polyostotic FD was diagnosed instead of McCune-Albright syndrome (MAS). The patient underwent craniotomy fistula repair surgery. The excised bone was contoured to be thinner to increase the cranial cavity. The patient recovered well and CSF leakage did not recur. But during a nineteen-month follow up, sight in the patient's left eye was decreased. MAS was suspected. Unfortunately the patient refused to take the proposed decompression surgery and laboratory tests of serum hormones. Conclusions: CFD, if the wall of the paranasal sinus is involved and the cranial cavity is decreased, may increase the risk of CSF rhinorrhea after head trauma. Expectant management is recommended in asymptomatic CFD patients even in the presence of optic nerve compression. As MAS may cause more problems, it should be precluded before polyostotic FD is diagnosed.

The reconstruction after peripheral nerve damage, especially for long-segment nerve defects, remains a clinical challenge. Autologous nerve graft transplantation is an efficient method for the repair of peripheral nerve defects, but the involved complications and shortcomings have greatly limited the clinical efficacy of treatments offered to patients with nerve defects. Thus, there is an urgent need to develop new therapeutic strategies and explore alternatives to autologous nerve transplantation in clinical practice, based on the knowledge of the peripheral nerve regeneration mechanism and biological histocompatibility principles. With significant advances in the research and application of nerve conduits, they have been used to repair peripheral nerve injury for several decades. In this paper, the study background of nerve conduits, their applications in clinic, status of conduit material research and construction of tissue-engineered artificial nerves were reviewed.

Objective: This study aimed to use a systematic approach to evaluate the current utilization, safety, and effectiveness of cell therapies for neurological diseases in human. And review the present regulations, considering United States (US) as a representative country, for cell transplantation in neurological disease and discuss the challenges facing the field of neurology in the coming decades. Methods: A detailed search was performed in systematic literature reviews of cellularbased therapies in neurological diseases, using PubMed, web of science, and clinical trials. Regulations of cell therapy products used for clinical trials were searched from the Food and Drug Administration (FDA) and the National Institutes of Health (NIH). Results: Seven most common types of cell therapies for neurological diseases have been reported to be relatively safe with varying degrees of neurological recovery. And a series of regulations in US for cellular therapy was summarized including preclinical evaluations, sourcing material, stem cell manufacturing and characterization, cell therapy product, and clinical trials. Conclusions: Stem cell-based therapy holds great promise for a cure of such diseases and will value a growing population of patients. However, regulatory permitting activity of the US in the sphere of stem cells, technologies of regenerative medicine and substitutive cell therapy are selective, theoretical and does not fit the existing norm and rules. Compiled well-defined regulations to guide the application of stem cell products for clinical trials should be formulated.

Objective: Real-time monitoring of cytokine secretion at the single immunocyte level, based on the concept of immune cells, sociology has been recently reported. However, the relationships between glioma-initiating cells (GICs) and host immune cells and their mutual interactions in the tumor microenvironment have not been directly observed and remain unclear.
Methods: The dual fluorescence tracing technique was applied to label the co-cultured GICs and host macrophages (Mø), and the interactions between the two types of cells were observed using a live cell imaging system. Fusion cells in the co-culture system were monocloned and proliferated in vitro and their social interactions were observed and recorded.
Results: Using real-time dynamic observation of target cells, 6 types of intercellular conjunction microtubes were found to function in the transfer of intercellular information between GICs and Mø; GICs and host Mø can fuse into hybrid cells after several rounds of mutual interactions, and then these fusion cells fused with each other; Fusion cells generated offspring cells through symmetrical and asymmetrical division or underwent apoptosis. A "cell in cell" phenomenon was observed in the fusion cells, which was often followed by cell release, namely entosis.
Conclusions: Preliminary studies revealed the patterns of cell conjunction via microtubes between GICs and host Mø and the processes of cell fusion, division, and entosis. The results revealed malignant transformation of host Mø, induced by GICs, suggesting complex social relationships among tumor-immune cells in gliomas.

Objective: The frontal lobe may be involved in circuits associated with depression, apathy, aggression, and other psychiatric symptoms. Although white matter changes (WMC) are related to the severity of behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease (AD), it is unclear which part of the WMC may play the most important role in BPSD. This study was designed to investigate the relationship between the location of WMC and the severity of BPSD in AD patients. Methods: Among patients diagnosed with Alzheimer's disease between 2009 and 2014, 387 patients were retrospectively reviewed after those with pre-existing organic brain syndrome, psychiatric diseases, or toxic-metabolic encephalopathy were excluded. Patients' demographic and laboratory data, WMC measured with brain computed tomography and scored using the age-related white matter changes (ARWMC) scale, and neuropsychological tests, including the cognitive abilities screening instrument (CASI), the Mini-Mental State Examination (MMSE), the clinical dementia rating scale with sum-box (CDR-SB), and the neuropsychiatric inventory (NPI) were analyzed. Results: There was no significant difference in the NPI between patients with and without a history of stroke, hypertension, and diabetes. No significant difference in the NPI was identified between different sexes or different Apolipoprotein E (APOE) alleles. The NPI score was significantly correlated with the duration of education (r = -0.4515,P = 0.0172), CASI (r = -0.2915, P < 0.0001), MMSE (r = -0.8476, P < 0.0001), and CDR-SB (r = 2.2839, P < 0.0001). WMC in the right frontal lobe showed a significant difference in NPI in comparison to those without WMC (P = 0.0255). After adjusting for age, duration of education, and CASI, WMC in the right frontal lobe remained significantly associated with the NPI score (β = 3.8934,P = 0.042). Conclusions: WMC involving the right frontal lobe may play an important role in the BPSD in AD patients during their dementia diagnosis. Further studies are necessary to confirm whether controlling the risk factors of WMC can slow the progression of BPSD.

Objective: To evaluate the clinical results of repairing skull defects with biomimetic bone (nano-hap/collagen composites, NHACs) in children. Methods: Thirteen children with skull defects were treated with NHACs in our hospital. The NHACs molded with the help of a 3D printer were used in the operations. Results: All 13 operations were successful, and patients recovered without infection. Only one patient suffered from subcutaneous hydrops post-operation. The implanted NHACs remained fixed well after 1 year, and their CT HU values raised gradually. Skull shapes of children developed normally. Recovery of neurological and cognitive function was significant. Conclusions: NHAC, chosen to repair skull defects in children, can coexist with normal skull and reduce the negative effects on growth and development. NHAC could be a good choice for children with skull defects.

Objectives: Nerve regeneration after peripheral nerve injury is a slow process with a limited degree of functional recovery, resulting in a high disability rate. Thus, accelerating the rate of nerve regeneration and improving the degree of nerve repair is a clinical challenge. This study aimed to investigate the role of growth factor gel combined with small-gap nerve anastomosis in the regeneration of sciatic nerve injury in rats. This was achieved by injecting nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) gel into a silicon chamber that bridged the transection of the nerve.
Methods: In 27 randomly chosen Sprague Dawley rats, a sharp blade was used to transect the right hind leg sciatic nerve. The rats were divided into 3 groups: in groups A and B, silicon tubes containing NGF and bFGF gel or saline, respectively, were used to bridge the nerve proximal and distal ends (3-mm gap), and in group C, the nerve proximal and distal ends were directly sutured. Eight weeks after surgery, the sciatic nerve function index, neural electrophysiology, and muscle wet weight as well as histological, ultrastructural, and immunohistochemical parameters were evaluated.
Results: The sciatic nerve function index, nerve conduction velocity, muscle wet weight, density of regenerated nerve fibers, and myelination in group A were better than those in group B or C, but the sciatic nerve function index, muscle wet weight, and thickness of myelination in the 3 groups were not significantly different (P > 0.05). There were no significant differences innerve conduction velocity between groups A and B (P > 0.05), but it was higher in both groups than that of group C (P < 0.05). The regenerated nerve fiber density in the 3 groups showed significant differences (P < 0.05).
Conclusions: Small-gap nerve anastomosis can provide a good regenerative microenvironment for rat sciatic nerve regeneration, and the combined strategy of growth factor gel with small-gap nerve anastomosis appears to have a superior effect on nerve repair.

Objectives: Adult medulloblastoma is a rare tumor, and few retrospective studies on medulloblastoma have been published to date. A standard treatment regimen has not yet been established. Accordingly, this study was designed to determine the treatment outcomes and prognostic factors for patients with adult medulloblastoma.
Methods: We retrospectively reviewed all cases of adult medulloblastoma at the Beijing Tiantan Hospital between 2004 and 2007. There were 33 patients in total. Tumor removal followed by radiotherapy was performed in all patients. Five patients received maintenance chemotherapy after radiotherapy. Statistical analysis was performed using the log-rank test, Kaplan-Meier method, and Cox regression analysis.
Results: The median follow-up period was 73 months. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 45.5% ± 8.7% and 51.5% ± 8.7%, respectively. Recurrence or progression was observed in 21 patients, and 14 patients were still alive. Tumor location at the midline with infiltration to the floor of the fourth ventricle was associated with the worst PFS and OS (P= 0.032). Hemispheric desmoplastic/nodular medulloblastomas (DNMBs) were associated with a better outcome than midline DNMB. The average-risk group tended to have a better 5-year PFS rate than the high-risk group (P= 0.065).
Conclusions: Tumor location is an important prognostic marker for adulthood MB. We propose a molecular and clinical staging system should be established for adulthood MB. Further prospective clinical trials should be performed to draw a conclusion.

The origin of neurosurgery dates back to the end of the 19th century. Many prominent and pioneering neurosurgeons contributed substantially to the development of skull base neurosurgery. In the naked eye era, Harvey Cushing promoted the delicate and meticulous surgical techniques, and significantly decreased the surgical mortality. In the 1960s, the operative microscope was introduced to the neurosurgery. Neurosurgeons represented by Yasargil took full advantage of this technology and pushed skull base neurosurgery into a new era. Transnasal transsphenoidal approach has long been used to resect pituitary tumor. The use of endoscope expands the transnasal exposure from the crista galli to C-2. The endoscopic approach may represent a paradigm shift, perhaps equivalent to the introduction of the microscope, in approaching various skull base lesions.

Depression is a frequent comorbid syndrome in Parkinson's disease. It is a difficult symptom to manage, as patients continuously receive antiparkinsonian medication and may also have to be treated for the amelioration of the side-effects of antiparkinsonian therapy. The first-line treatment for depression in Parkinson's disease is the use of selective serotonin reuptake inhibitors (SSRIs). The clinical efficacy of these medications in patients with Parkinson's disease is questionable. In fact, based on their mechanism of action, which requires at least a functional serotonergic system, it is predicted that SSRIs will have lower efficacy in patients with Parkinson's disease. Here, we consider the mechanism of action of SSRIs in the context of Parkinson's disease by investigating the fall in the levels of serotonergic markers and the inhibitory outcomes of antiparkinsonian treatment on serotonergic nerve activity. Because certain classes of antidepressant drugs are widely available, it is necessary to perform translational research to address different strategies used to manage depression in Parkinson's disease.

Few studies have investigated the factors associated with the prognosis of children with medulloblastoma. This retrospective observational study evaluated the association of molecular subtype, clinical characteristics, and pathological types with the outcomes of children with medulloblastoma. This study included 40 patients with medulloblastoma who underwent surgical resection at the Affiliated Children's Hospital of Fudan University between January 2004 and June 2014. The primary outcome was overall survival (OS). Risk factors associated with survival, disease progression, and recurrence were analyzed by univariate Cox regression analysis; the identified significant risk factors were further analyzed by Kaplan-Meier survival curves. Immunohistochemistry analysis of Yes-associated protein 1 (YAP1) and GRB2-associated protein 1 (GAB1) was used for medulloblastoma subtype identification; 20% of tumors were the WNT subtype, and 32.5% were the SHH subtype, with the remainder being non-SHH/WNT. Factors associated with OS included M stage, calcification, cerebrospinal fluid fistula, postoperative treatment (radiotherapy, chemotherapy, or both), postoperative Karnofsky Performance Scale score, and molecular subtype (P < 0.044). Patients with the WNT subtype had better survival outcomes (hazard ratio [HR] = 0.16, 95% confidence interval [CI]: 0.05–0.58). Number of symptoms, M stage, and postoperative radiotherapy were associated with disease progression (P ≤ 0.033). The risk of recurrence increased with advanced M stage (HR = 30.71; 95% CI: 3.92–240.44, P = 0.001). Patients receiving both chemotherapy and radiotherapy were less likely to have a recurrence (P = 0.040). Molecular subtyping of medulloblastoma was more predictive of survival than histopathology in patients undergoing adjuvant therapy.

Objectives: Recent findings have further highlighted the role of the thyroid system in the pathophysiology of depression and revealed new physiologically relevant elements of the thyroid system. Our previous study showed an antidepressant-like effect of 3,5-diiodo-L-thyronine (T2), which was previously considered to be a physiologically inactive molecule, in mice. Here, we aimed to investigate the antidepressant-like effects of T2 further.
Methods: We studied the effects of bolus injections of T2 to C57Bl6J mice at doses of 0.25 or 0.75 mg/kg with the tail suspension and forced swim models. The effects of the higher dose were investigated in CD1 mice in the forced swim test. Potential behavioral effects of these treatments were also studied using the novel cage and dark-light box tests.
Results: A reduction of depressive-like behavior was found in mice treated with 0.75 mg/kg of T2 in the tail suspension test, but not in the forced swim test. Locomotion and anxiety variables were unaltered following treatment with T2. There were no significant changes after bolus administration of 0.25 mg/kg T2 in either test for depressive-like behavior. Thus, bolus injection of T2 at the dose 0.75 mg/kg can induce antidepressant-like effects without affecting other behaviors.
Conclusions: A discrepant result in the forced swim test may be due to its different sensitivity to T2 compared with the tail suspension paradigm. Furthermore, the development of procedural modifications of this model can be useful in its application in pre-clinical studies.

Objective: The conflicting findings of previous morphological studies on intracranial aneurysm rupture may be caused by the different locations of aneurysms. We aimed to determine the independent risk factors of aneurysm rupture by focusing on only posterior communicating artery (PcomA) aneurysms. Methods: In 89 PcomA aneurysms (58 ruptured, 31 unruptured), clinical and morphological characteristics were compared between the ruptured and unruptured groups. Multivariate logistic regression analysis was performed to determine the independent predictors for the rupture status of PcomA aneurysms. Results: In univariate analyses, the aneurysm dome size, aspect ratio, size ratio, dome-to-neck ratio, and inflow angle were significant parameters. With multivariate analyses, only the aneurysm dome size and inflow angle were significantly associated with the rupture status of PcomA aneurysms. Conclusions: Morphology was related with rupture of PcomA aneurysms. The aneurysm dome size and inflow angle were found to be the independent parameters characterizing the rupture status of PcomA aneurysms.

Objective: To design a new open-end intracranial hematoma drainage tube for clinical application.
Methods: The newly developed device consists of two parts:the plunger and barrel. On one side, the barrel is bullet shaped with an opening tip. The plunger is located in the middle cavity of the tube barrel and extended out at the open-end. It was designed for strengthening the tube barrel and for convenience in performing the drainage procedure. It can be used by inserting the drainage tube into the lesion and pulling out the plunger, whereby blood will forcefully rise up inside the barrel, providing a satisfactory outcome. It is made for effusion drainage purposes. During the procedure, the drainage tip is placed at the deepest part of the intracranial hematoma to completely drain the blood. Moreover, the plunger fits tightly in the tube, preventing leakage during the operation. With the use of the device, brain can be separated. In addition, the device can help reduce the risk of cerebral damage because of the small operating area. The barrel sidewall has matching opening holes bilaterally and equally for exchanging substances between the inner and outer parts. The overlapping ratio in each horizontal pair is around 1/3-1/2. Each pair on the opposite side will form a different pressure. Thus, the opening holes will not easily get blocked with blood clot.
Results: Blood and accumulated liquid from the deepest part of the intracranial hematoma can be directly drawn through the drainage tube without damaging a large area. The tube does not get blocked easily and allows for complete removal of the hematoma.
Conclusions: The device is asuitable instrument for clinical application.

Alzheimer's disease (AD) is the most prevalent type of dementia, and its neuropathology is characterized by the deposition of insoluble β-amyloid (Aβ) peptides, intracellular neurofibrillary tangles, amyloid angiopathy, age-related brain atrophy, synaptic pathology, white matter rarefaction, granulovacuolar degeneration, neuron loss, and neuroinflammation. Although much is known about the neurobiology of AD, very few conventional therapies are available to arrest or slow the disease. There is an urgent need for novel therapeutic approaches for AD. AD subjects have significantly fewer viable precursor cells in the hippocampus compared with age-matched healthy control subjects. However, the viable precursor cells that remain in AD and age-matched healthy control brain specimens can be induced to differentiate. To facilitate or mimic the natural compensatory effect in AD, cell therapy, including endogenous and exogenous stem cells, has been considered in AD. In this review, we focus on the history and development of cell therapy in AD, and consider the role of cell therapy as a potential treatment for AD.

The skull provides protection and mechanical support, and acts as a container for the brain and its accessory organs. Some defects in the skull can fatally threaten human life. Many efforts have been taken to repair defects in the skull, among which cranioplasty is the most prominent technique. To repair the injury, numerous natural and artificial materials have been adopted by neurosurgeons. Many cranioprostheses have been tried in the past decades, from autoplast to bioceramics. Neurosurgeons have been evaluating their advantages and shortages through clinical practice. Among those prostheses, surgeons gradually prefer bionic ones due to their marvelous osteoconductivity, osteoinductivity, biocompatibility, and biodegradability. Autogeneic bone has been widely recognized as the “gold standard” for renovating large-sized bone defects. However, the access to this technique is restricted by limited availability and complications associated with its use. Many metal and polymeric materials with mechanical characteristics analogous to natural bones were consequently applied to cranioplasty. But most of them were unsatisfactory concerning osteoconductiion and biodegradability owe to their intrinsic properties. With the microstructures almost identical to natural bones, mineralized collagen has biological performance nearly identical to autogeneic bone, such as osteoconduction. Implants made of mineralized collagen can integrate themselves into the newly formed bones through a process called “creeping substitution”. In this review, the authors retrospect the evolution of skull repair material applied in cranioplasty. The ultimate skull repair material should have microstructure and bioactive qualities that enable osteogenesis induction and intramembranous ossification.

Post-stroke neuropsychiatric (NP) disorders are common and have complex etiologies. Multiple factors such as lesion location, personality characteristics, socioeconomic status, pre-stroke psychiatric history, and family support are the determining factors in most cases. Although depression and anxiety are more common, emotional incontinence and catastrophic reactions are also frequently observed. Post-stroke depression (PSD) has been associated with an increased risk of stroke recurrence. Despite its serious consequences and high prevalence, PSD remains undetected and untreated. Treatment options of NP disorders depend on severity, presentation at the time of diagnosis, and patient cooperation, and include antidepressants, mood stabilizers, exercise therapy, psychotherapy, and even revascularization. The efficient management of NP disorders improves outcomes, quality of life, and survival rates in post-stroke patients. However, very few studies have identified definitive treatment for these patients; therefore, further research is required.

Objective: Primary intracranial malignant fibrous histiocytoma (MFH) is rare. We describe the detailed clinical features of 8 cases and fully review the literature to evaluate several prognostic factors. Methods: Eight patients with pathologically confirmed primary intracranial MFH were retrospectively reviewed. We searched PubMed for relevant articles with the term "intracranial malignant fibrous histiocytoma". Results: Of the 8 patients, 4 were men and 4 were women. Three patients had received previous radiotherapy. The age of the patients ranged from 19 to 69 years, with a median age of 48 years. Most tumors could be totally resected; and only 1 tumor was subtotally resected. Six patients received postoperative radiotherapy and 3 patients received postoperative chemotherapy. Most patients died within the first year after surgery; and only 1 patient was still alive on the date of the last follow-up. We reviewed the literature and included a total of 46 patients in the Kaplan-Meier survival analysis. Young patients (less than 30 years old) seemed to have a better prognosis and survival rate than older patients (more than 30 years old) (log-rank test, P=0.008). However, sex (P=0.675), extent of resection (P=0.934), postoperative radiotherapy (P=0.592), and postoperative chemotherapy (P=0.424) did not affect patient prognosis. Conclusions: The prognosis of MFH is usually poor, and most patients die within the first year after surgery. Younger MFH patients (less than 30 years old) seem to have a better prognosis and improved survival compared to older patients.

Objective: The authors report an extremely unusual presentation and management of a children pineal mixed germ cell tumor mainly composed of immature teratoma, aiming to summarize main theraptic points by literature review. Methods: A cystic lesion located in the rear of third ventricle in a child was detected 3 years ago with no other therapy performed except for a ventriculo-peritoneal shunt. During the following 3 years, intermitted regular brain MRI demonstrated no evidence of lesion aggrandizement. However from 20 days before admission to our institute the patient began to present acutely with exacerbating clinical symptoms meanwhile brain MRI showed signs of abrupt revulsions of initial lesion without any incentive cause. Neurological examination revealed a significant rising of serum tumor marker level. Then surgical resection was performed immediately after admission which was followed by correlative two-course chemotherapy. Results: Postoperative brain MRI demonstrated totally removing of the lesion in rear of third ventricle. Serum tumor marker level decreased remarkably after surgery and declined to normal level after two-course chemotherapy. No obvious neurological deficit occurred except for short-term memory difficulty which gradually recovered within two weeks. Soon after the second course chemotherapy the patient was currently asymptomatic and returned to school. Conclusions: (1) To ensure definitive diagnosis and proper therapecutic protocols benefit from grasping clinical features of mixed germ cell tumor. (2) Overall preoperative investigation including serum tumor marker level is as critical as neurological imaging examination. (3) Surgical excision is confirmed to be the key modality of treatment. With the regarding of mixed germ cell tumor, never highlight total resection too much. (4) Postoperative adjuvant chemotherapy is recommended as further intensive treatment to improve the prognosis of mix germ cell tumor.

Objectives: Currently, the clinical repair of sciatic nerve injury remains difficult. Previous studies have confirmed that transplantation of adipose tissue-derived stem cells promotes nerve regeneration and restoration at peripheral nerve injury sites.
Methods: In this study, adipose tissue-derived stem cells were induced to differentiate into neural progenitor cells, transfected with a green fluorescent protein-containing lentivirus, and then transplanted into the lesions of rats with sciatic nerve compression injury.
Results: Fluorescence microscopy revealed that the transplanted cells survived, migrated, and differentiated in rats. At two weeks post-operation, a large number of transplanted cells had migrated to the injured lesions; at six weeks post-operation, transplanted cells were visible around the injured nerve and several cells were observed to express a Schwann cell marker. Sciatic function index and electrophysiological outcomes of the transplantation group were better than those of the control group. Cell transplantation promoted the recovery of motor nerve conduction velocity and compound muscle action potential amplitude, and reduced gastrocnemius muscle atrophy.
Conclusions: Our experimental findings indicate that neural progenitor cells, differentiated from adipose tissue-derived stem cells, are potential seed stem cells that can be transplanted into lesions to treat sciatic nerve injury. This provides a theoretical basis for their use in clinical applications.

Objective: To study the effects of regional cerebral blood flow (rCBF) perfusion on learning and memory function in special brain areas and its molecular mechanism in rat. Methods: Sixty-four adult male healthy Sprague-Dawley (SD) rats were randomly divided into two groups: A false operation group and an operation group. The false operation group was randomly divided into four subgroups (A₀, B₀, C₀, and D₀) and the operation group was randomly divided into four subgroups (A, B, C, and D), with eight rats in each subgroup. The operation group underwent bilateral common carotid artery permanent ligation, while the other group only underwent a skin incision without the bilateral common carotid artery permanent ligation. Learning memory function of rats in each subgroup was measured using a Y-maze at 4 h, 8 h, 24 h, and 3 days after surgery. The rCBF in the right frontal lobe and hippocampus was detected using the Periflux PF model laser Doppler flowmetry and c-fos, c-jun, Bcl-2, and Bax protein expression in the right frontal lobe and hippocampus was measured using immunohistochemistry. Results: The rCBF in the right frontal lobule division and right hippocampus division was significantly lower in the operation group than in the false operation group (P < 0.05). The error number (EN), time to reach the target, and total reaction time (TRT) for the learning index using the Y-type labyrinth test in the operation group were significantly higher than that in the false operation group (P < 0.05); however, the active avoid rate in the operation group was significantly lower than that of the false operation group. Expression of c-fos and c-jun as well as the average absorbency in the right frontal lobule division and right hippocampus division in the operation group were significantly higher than those in the false operation group (P < 0.05). The number of Bax and Bcl-2-positive cells was significantly higher in the operation group, and the expression ratio of Bax/Bcl-2 in the operation group was significantly higher than that in the false operation group (P < 0.01). Conclusions: rCBF decrease can impair learning and memory function in rats, which may be related to the increased expression of c-fos, c-jun, Bcl-2, and Bax proteins in the t he frontal cortex and hippocampus.

Objectives: To study the effect of fetal stem cell (FSC) therapy on Grade Ⅰ and Ⅱ respiratory failure in patients with amyotrophic lateral sclerosis (ALS) and muscular dystrophy (MD).
Methods: A comparative study was conducted on 41 patients with Grade Ⅰ or Ⅱ respiratory failure (RF) resulting from ALS or MD. The patients were divided into 4 groups according to the underlying disease and the degree of RF. Patients underwent combined treatment, including the experimental application of FSC therapy, and were examined before FSC treatment, and 6 months and 12 months after treatment.
Results: FSC treatment improved both subjective and objective breathing parameters as early as 6 months post-treatment. A significant increase in the forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV₁) was reported by all patients with grade Ⅰ RF linked to ALS and MD compared to baseline. Patient respiratory improvement was maintained over the next 6 months. Grade Ⅱ RF patients with MD reported a significant improvement in FVC 12 months after treatment.
Conclusions: Evidence for respiratory improvement was observed as early as 6 months in all patients after combined treatment including FSC therapy, and this was maintained for a further 6 months after therapy. In MD patients with Grade Ⅱ RF, treatment resulted in a significant FVC and FEV₁ increase within 6 months and downgrading to Grade Ⅰ RF within a year after FSC treatment.

Mesenchymal stromal/stem cells (MSCs) are multipotent cells under consideration as a potential new therapy for a variety of inflammatory diseases including certain neurological disorders. It is generally thought that the efficacy of cell therapy in attenuating damage after ischemia, inflammation, or injury depends on the quantity of transplanted cells recruited to the target tissue. However, only a small number of systematically infused MSCs can effectively migrate to target sites, which significantly decreases the efficacy of exogenous cell-based therapy. In this review, we discuss specific factors influencing MSC migration, and summarize current strategies that effectively promote the motility of MSCs. In addition, we describe several protocols to improve the migration of stromal cells into the nervous system and, therefore, enhance the efficiency of engraftment as means of treating neurological disorders.

Objectives: To discuss the bleeding mechanisms after removing a medulla oblongata hemangioblastoma. Methods: A 42-year-old male patient was diagnosed with a medulla oblongata hemangioblastoma. Preoperative cranial magnetic resonance imaging, computed tomography angiography and post-surgery computed tomography were completed during clinical procedure. We also reviewed the related literatures. Results: The preoperative computed tomography angiography did not demonstrate any intracranial aneurysm. But, the patient had a fatal subarachnoid hemorrhage with ventricular hemorrhage 4 hours after surgery following the post-surgery computed tomography. Conclusions: Subarachnoid hemorrhage after surgery of the medulla oblongata hemangioblastoma is very rare. Delayed postoperative hemorrhage seems the most reasonable explanation of Subarachnoid hemorrhage in our case.

Objective: We sought to investigate the efficacy of oral dosing in mice with imipramine (7mg/kg/day) via water or in food pellets, and to compare its effects in the paradigms of learned helplessness, locomotion, hedonic state, and anxiety. Methods: Water and food consumption were measured to determine daily imipramine dosage in C57BL/6N mice. Next, baseline scores for O-maze, dark/light box, and sucrose tests were measured. Mice were then subjected to a 4-week treatment of voluntary ingestion of drinking water or food pellets containing imipramine. Lastly, all groups were subjected to novel cage, open field, O-maze, dark/light box, sucrose test, and forced swim test to assess the effects of the treatment. Results: In naïve mice, imipramine delivered via food, induced a reduction of total floating and increased latency in the forced swim test, i.e., antidepressant-like effects. No other significant effects were found. Dosing with water did not change behavior in the forced swim, sucrose preference test, anxiety, or locomotor paradigms, but increased exploration in the novel cage. Conclusions: Voluntary ingestion is an effective method of chronic dosing with imipramine in naïve mice. Delivery of imipramine with food pellets elicits antidepressant-like effects in the forced swim test, with no effects on anxiety, locomotion, or preference behaviors. In contrast, no such effects were observed with treatment via drinking water, suggesting that a higher dose may be required. Our work argues for a broader use of oral delivery using food-treated pellets, in small rodent models of pre-clinical depression. It may substantially improve animal welfare and overcome potential confounds in translational research, which are frequently associated with adverse chronic invasive pharmacotherapies.

Objective: To study the influence of different microsurgical methods on surgical outcomes and complications, and to improve the surgical outcomes for trigeminal neuralgia. Methods: The clinical data of 109 patients with trigeminal neuralgia, who were treated with microsurgery, were analyzed retrospectively. All patients were divided into 3 groups according to surgical modality: the trigeminal neuralgia decompression group (TND group, 19 patients), the TND and rhizotomy group (rhizotomy group, 55 patients), and the TND and selective lesioning group (lesioning group, 35 patients). The mid-term and short-term effects of microsurgery, and the occurrences of complications, were compared between the 3 groups. Results: There were no statistical differences in the frequency of complications between the 3 groups (P>0.05). Eighty-four patients were followed up for 6 to 33 months. The rate of pain disappearance was found to be 94.4% in the TND group, and 100% in both the rhizotomy and lesioning groups; thus, no significant differences were found between these 3 groups (P>0.05). Additionally, 50% of the patients in the rhizotomy group and 3.6% of the patients in the lesioning group had facial numbness while no patients were affected with facial numbness in the TND group, and the differences between these 3 groups were significant (P<0.05). Conclusions: Microsurgery is effective and safe for trigeminal neuralgia. The use of TND, in combination with selective lesioning, ensures therapeutic efficacy and improves the quality of life in postoperative patients.

The apolipoprotein E (APOE) ε4 allelle is a well-established risk factor for cognitive decline. Racial factors may mitigate its effects. However, APOE ε4 has similar effects even among different racial groups. The APOE genotype in patients with Alzheimer's disease may influence therapeutic decisions.

Non-invasive neuroimaging plays a crucial role in the assessment of the human spinal cord, but it is quite challenging. Magnetic resonance imaging (MRI) is an important modality to obtain both high-resolution anatomical and functional information concerning the spinal cord. Besides conventional MRI, advanced MRI techniques could provide novel information about the microstructure and neural function of the spinal cord, thereby enhancing the understanding of spinal cord neurology and pathology of various spinal disorders.

Objective: This study aimed to employ time-resolved spectroscopy (TRS) to explore age-related differences in prefrontal cortex (PFC) activity while subjects performed a working memory task. Methods: We employed TRS to measure PFC activity in ten healthy younger and ten healthy older subjects while they performed a working memory (WM) task. All subjects performed the Sternberg test (ST) in which the memory-set size varied between one and six digits. Using TRS, we recorded changes in cerebral blood oxygenation as a measure of changes in PFC activity during the task. In order to identify left/right asymmetry of PFC activity during the working memory task, we calculated the laterality score, i.e., Δoxy-Hb (right Δoxy-Hb—left Δoxy-Hb); positive values indicate greater activity in the right PFC, while negative values indicate greater activity in the left PFC. Results: During the ST, statistical analyses showed no significant differences between the younger and older groups in accuracy for low memory-load and high memoryload. In high memory-load tasks, however, older subjects were slower than younger subjects (P < 0.05). We found that the younger group showed right lateral responses with a stronger right than left activation in the frontal pole, whereas the older group showed bilateral responses (P < 0.05). Conclusions: The present results are consistent with the hemispheric asymmetry reduction in older adults (HAROLD) model; working memory tasks cause asymmetrical PFC activation in younger adults, while older adults tend to show reduced hemispheric lateralization.

Objective: Cavernous malformation (CM) originating from the hypothalamus is extremely rare and the deep location presents a challenge for its neurosurgical management. We report such a case to better understand its clinical features. Methods and Results: A 40-year-old male patient presented with impaired vision in the left eye. Magnetic resonance imaging (MRI) revealed a regularly shaped round lesion located in the suprasellar cistern, and a clinical diagnosis of hypothalamic CM was made. Complete microsurgical excision was performed via a right pterional craniotomy. The patient showed good recovery with no further visual acuity or field deficits postoperatively. No CM recurrence or rebleeding was seen on follow-up MRI scans performed over the course of two years. Conclusions: For patients with cavernous malformation in the hypothalamus, accurate preoperative diagnosis with complete surgical removal by an appropriate surgical approach can contribute to satisfactory outcomes.

Objectives: Sellar gangliocytomas are extremely rare. Since they present clinically and radiologically as pituitary adenomas, the preoperative diagnosis of these mixed tumors is very difficult. Here, we report three cases of gangliocytoma combined with pituitary adenoma and describe our findings. Methods: The clinical data of the three cases of gangliocytoma combined with pituitary adenoma have been retrospectively analyzed, and the published literature has also been reviewed. Results: All three patients underwent pure endonasal endoscopic surgery, and no recurrence was observed over a follow-up of at least 30 months. Growth hormone (GH)-hypersecreting adenoma and tumor calcification were detected in these mixed tumors. Conclusions: Pure endoscopic transnasal transsphenoidal surgery may be an effective way for the treatment of this kind of tumor. Gross total resection of the tumor is recommended. In addition, calcification with GH-hypersecretion may serve as a preoperative diagnostic clue for gangliocytoma in the sella turcica.