关键词： Osthole   Mechanical brain injury   Notch signaling pathway   Endogenous NSCs proliferation  

摘要： Mechanical brain injury (MBI) is a common neurotrosis disorder of the central nervous system (CNS), which has a higher mortality and disability. In the case of MBI, neurons death leads to loss of nerve function. To date, there was no satisfactory way to restore neural deficits caused by MBI. Endogenous neural stem cells (NSCs) can proliferate, differentiate and migrate to the lesions after brain injury, to replace and repair the damaged neural cells in the subventricular zone (SVZ), hippocampus and the regions of brain injury. In the present study, we first prepared a mouse model of cortical stab wound brain injury. Using the immunohistochemical and hematoxylin-eosin (H&E) staining method, we demonstrated that osthole (Ost), a natural coumarin derivative, was capable of promoting the proliferation of endogenous NSCs and improving neuronal restoration. Then, using the Morris water maze (MWM) test, we revealed that Ost significantly improved the learning and memory function in the MBI mice, increased the number of neurons in the regions of brain injury, hippocampus DG and CA3 regions. Additionally, we found that Ost up regulated the expression of self-renewal genes Notch 1 and Hes 1. However, when Notch activity was blocked by the gamma-secretase inhibitor DAPT, the expression of Notch 1 and Hes 1 mRNA was down regulated, augmentation of NICD and Hes 1 protein was ameliorated, the proliferation-inducing effect of Ost was abolished. These results suggested that the effects of Ost were at least in part mediated by activation of Notch signaling pathway. Our findings support that Ost is a potential drug for treating MBI due to its neuronal restoration. (C) 2017 Elsevier Inc. All rights reserved.

关键词： Schizophrenia   Epilepsy   Multiple Sclerosis   VRK2  

摘要： Background: Schizophrenia (SCZ), epilepsy and Multiple Sclerosis (MS) are neurological disorders with increasing prevalence disturb the patients' lives and are regarded as burdens to the society. As multifactorial disorders, genetic susceptibility factors are involved in their pathogenesis. The Vaccinia-Related Kinase 2 (VRK2) gene codes for a serine threonine kinase recently reported to be contributed in the pathogenesis of some neurological disorders. In the present case-control study we compared the VRK2 gene expression in peripheral blood samples from SCZ, epilepsy and MS patients with normal subjects. Method: A total of 300 subjects comprising 50 patients in each disease category (SCZ, epilepsy and MS) as well as 150 healthy individuals (50 matched controls for each disorder) participated in the current study. Result: The VRK2 blood mRNA expression level was measured using the TaqMan real time PCR. The results demonstrated significant down-regulation of VRK2 gene in SCZ (P< 0.0001), epilepsy (P= 0.008) and MS (P= 0.029) compared with the healthy subjects. Conclusion: Consequently, VRK2 is suggested as a candidate gene for neurological disorders through its role in signaling pathway, the neuronal loss and stress response.

关键词： Transient neurological deficit   TIA   Migraine   Epilepsy   EEG   Stroke mimics  

摘要： Identification of stroke mimics and 'chameleons' among transient neurological deficits (TND) is critical. Diagnostic workup consists of a brain imaging study, for a vascular disease or a brain tumour and EEG, for epileptiform discharges. The precise role of EEG in this diagnostic workup has, however, never been clearly delineated. However, this could be crucial in cases of atypical or incomplete presentation with consequences on disease management and treatment. We analysed the EEG patterns on 95 consecutive patients referred for an EEG within 7 days of a TND with diagnostic uncertainty. Patients were classified at the discharge or the 3-month follow-up visit as: 'ischemic origin', 'migraine aura', 'focal seizure', and 'other'. All patients had a brain imaging study. EEG characteristics were correlated to the TND symptoms, imaging study, and final diagnosis. Sixty four (67%) were of acute onset. Median symptom duration was 45 min. Thirty two % were 'ischemic', 14% 'migraine aura', 19% 'focal seizure', and 36% 'other' cause. EEGs were recorded with a median delay of 1.6 day after symptoms onset. Forty EEGs (42%) were abnormal. Focal slow waves were the most common finding (43%), also in the ischemic group (43%), whether patients had a typical presentation or not. Epileptiform discharges were found in three patients, one with focal seizure and two with migraine aura. Non-specific EEG focal slowing is commonly found in TND, and may last several days. We found no difference in EEG presentation between stroke mimics and stroke chameleons, and between other diagnoses.

关键词： MECHANISM of action (Biochemistry)   TRIGLYCERIDES   KETOGENIC diet   METABOLIC disorders   TREATMENT of epilepsy   NEUROLOGICAL disorders  

摘要： High-fat, low-carbohydrate diets, known as ketogenic diets, have been used as a non-pharmacological treatment for refractory epilepsy. A key mechanism of this treatment is thought to be the generation of ketones, which provide brain cells (neurons and astrocytes) with an energy source that is more efficient than glucose, resulting in beneficial downstream metabolic changes, such as increasing adenosine levels, which might have effects on seizure control. However, some studies have challenged the central role of ketones because medium-chain fatty acids, which are part of a commonly used variation of the diet (the medium-chain triglyceride ketogenic diet), have been shown to directly inhibit AMPA receptors (glutamate receptors), and to change cell energetics through mitochondrial biogenesis. Through these mechanisms, medium-chain fatty acids rather than ketones are likely to block seizure onset and raise seizure threshold. The mechanisms underlying the ketogenic diet might also have roles in other disorders, such as preventing neurodegeneration in Alzheimer's disease, the proliferation and spread of cancer, and insulin resistance in type 2 diabetes. Analysing medium-chain fatty acids in future ketogenic diet studies will provide further insights into their importance in modified forms of the diet. Moreover, the results of these studies could facilitate the development of new pharmacological and dietary therapies for epilepsy and other disorders.

关键词： Anti-VEGF treatment   Neurological function   Schwannoma  

摘要： Research of various diseases of the nervous system has shown that VEGF has direct neuroprotective effects in the central and peripheral nervous systems, and indirect effects on improving neuronal vessel perfusion which leads to nerve protection. In the tumors of the nervous system, VEGF plays a critical role in tumor angiogenesis and tumor progression. The effect of anti-VEGF treatment on nerve protection and function has been recently reported - by normalizing the tumor vasculature, anti-VEGF treatment is able to relieve nerve edema and deliver oxygen more efficiently into the nerve, thus reducing nerve damage and improving nerve function. This review aims to summarize the divergent roles of VEGF in diseases of the nervous system and the recent findings of anti-VEGF therapy in nerve damage/regeneration and function in tumors, specifically, in Neurofibromatosis type 2 associated schwannomas.

关键词： Acute stroke   Deterioration   Thrombolysis   Penumbra   Cerebral ischemia  

摘要： Early neurological deterioration (END) following acute ischemic stroke is a serious clinical event strongly associated with poor outcome. Regarding specifically END occurring within 24 h following stroke onset, apart from straightforward causes such as symptomatic intracranial haemorrhage and malignant edema, the cause of END remains unclear in more than a half of cases. In the latter situation, patients are often referred to as 'progressive stroke', a default clinical category that does not imply underlying mechanisms, precluding informed management. In this review article, we summarize the available evidence on the incidence, predictors, and associated factors of unexplained END, and discuss its underlying pathophysiology. We particularly address the hemodynamic and thrombotic mechanisms that likely play a critical role in unexplained END, and in turn highlight potential new avenues to prevent and manage this ominous event.

关键词： journals   news  

关键词： vascular endothelial growth factor   cerebrovascular disease   stroke   hydrocephalus   neurological disorders  

摘要： Vascular endothelial growth factor (VEGF) is a potent growth factor playing diverse roles in vasculogenesis and angiogenesis. In the brain, VEGF mediates angiogenesis, neural migration and neuroprotection. As a permeability factor, excessive VEGF disrupts intracellular barriers, increases leakage of the choroid plexus endothelia, evokes edema, and activates the inflammatory pathway. Recently, we discovered that a heparin binding epidermal growth factor like growth factor (HB-EGF)a class of EGF receptor (EGFR) family ligandscontributes to the development of hydrocephalus with subarachnoid hemorrhage through activation of VEGF signaling. The objective of this review is to entail a recent update on causes of death due to neurological disorders involving cerebrovascular and age-related neurological conditions and to understand the mechanism by which angiogenesis-dependent pathological events can be treated with VEGF antagonisms. The Global Burden of Disease study indicates that cancer and cardiovascular disease including ischemic and hemorrhagic stroke are two leading causes of death worldwide. The literature suggests that VEGF signaling in ischemic brains highlights the importance of concentration, timing, and alternate route of modulating VEGF signaling pathway. Molecular targets distinguishing two distinct pathways of VEGF signaling may provide novel therapies for the treatment of neurological disorders and for maintaining lower mortality due to these conditions.

关键词： Gliomas   Monitoring   Functional   Score   Outcome   Awake surgery   Craniotomy  

摘要： Objective: In this prospective study, we assessed the utility of a novel prognostic score (PS) in guiding the surgical strategy of patients with sensorimotor area gliomas. Patients and methods: Form December 2012 to April 2016, we collected data from patients diagnosed with brain gliomas in the sensorimotor area. All the patients had intraoperatively confirmed contiguity or continuity with sensorimotor cortical and subcortical structures. Several clinical and radiological factors were analyzed to generate a PS for each patient (range 1-8). The end-points included the extent of resection (EOR) and neurological outcome (modified Rankin Score;mRS). We assessed the predictive power of the PS using different analyses. Crosstabs analyses and Fisher's exact test (Fet) were used to evaluate the possible predictive parameters, and for the classification of positive or negative outcomes for the chosen proxies;the significance threshold was set at p < 0.05. Results: Using independent t-tests, we compared the mRS at different time points (pre, post, and at 6 months) for 2 subgroups from the total sample using a cut-off PS value of 4. For the EOR, a PS value of was predictive of successful outcome, a value of <= 4 indicated an uncertain outcome, and a value of <= 3 predicted a worse outcome. Conclusions: This PS value can be easily used in clinical settings to help predict the functional outcome and EOR in sensorimotor area tumors. Integration with information from fMRI, DTI, and TMS, along with MRI spectroscopy could further enhance the value of this PS.

摘要： Introduction: In this study we examined the feasibility of assessing motor milestone performance of infants with spinal muscular atrophy (SMA) using the Hammersmith Infant Neurological Exam-Part 2 (HINE-2) in a phase 2 study of nusinersen. Methods: Nineteen SMA infants were assessed using the HINE-2 at baseline (<= 7 months of age), and periodically up to 39 months of age. We evaluated whether the HINE-2 was feasible, reliable, and sensitive to change. Results: Motor milestone assessments in SMA infants were feasible using the HINE-2. Baseline test-retest reliability was excellent (R 5 0.987;P < 0.0001). SMA infants were extremely low functioning at baseline and the HINE-2 was able to detect changes over time in 16 of 19 infants within all 8 domains. HINE-2 improvements were correlated with changes in other neuromuscular outcome measures. Discussion: Results support the use of the HINE-2 motor milestone assessment in clinical trials of SMA infants.