关键词： astrocytes   ischemic stroke   MANF   microglia   neurogenesis   neuroprotection   TREM2  

摘要： Aims Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a secretory neurotrophic factor protein that promotes repair after neuronal injury. The microglia cell surface receptor (triggering receptor expressed on myeloid cells-2;TREM2) regulates the production of pro- and antiinflammatory mediators after stroke. Here, we study MANF and TREM2 expression after middle cerebral artery occlusion (MCAo) and explore if docosahexaenoic acid (DHA) treatment exerts a potentiating effect. Methods We used 2 hours of the MCAo model in rats and intravenously administered DHA or vehicle at 3 hours after the onset of MCAo. Neurobehavioral assessment was performed on days 1, 3, 7, and 14;MANF and TREM2 expression was measured by immunohistochemistry and Western blotting. Results MANF was upregulated in neurons and astrocytes on days 1, 7, and 14, and TREM2 was expressed on macrophages in the ischemic penumbra and dentate gyrus (DG) on days 7 and 14. DHA improved neurobehavioral recovery, attenuated infarct size on days 7 and 14, increased MANF and decreased TREM2 expression in ischemic core, penumbra, DG, and enhanced neurogenesis on Day 14. Conclusion MANF and TREM2 protein abundance is robustly increased after MCAo, and DHA treatment potentiated MANF abundance, decreased TREM2 expression, improved neurobehavioral recovery, reduced infarction, and provided enhanced neuroprotection.

关键词： Glioblastoma   Imaging   Neuropathology   Surgery   Radiation therapy   Chemotherapy   Targeted therapy   Immunotherapy  

摘要： Target population These recommendations apply to adult patients with newly diagnosed or suspected glioblastoma. Imaging Question What imaging modalities are in development that may be able to provide improvements in diagnosis, and therapeutic guidance for individuals with newly diagnosed glioblastoma? Recommendation Level III: It is suggested that techniques utilizing magnetic resonance imaging for diffusion weighted imaging, and to measure cerebral blood and magnetic spectroscopic resonance imaging of N-acetyl aspartate, choline and the choline to N-acetyl aspartate index to assist in diagnosis and treatment planning in patients with newly diagnosed or suspected glioblastoma. Surgery Question What new surgical techniques can be used to provide improved tumor definition and resectability to yield better tumor control and prognosis for individuals with newly diagnosed glioblastoma? Recommendations Level II: The use of 5-aminolevulinic acid is recommended to improve extent of tumor resection in patients with newly diagnosed glioblastoma. Level II: The use of 5-aminolevulinic acid is recommended to improve median survival and 2 year survival in newly diagnosed glioblastoma patients with clinical characteristics suggesting poor prognosis. Level III: It is suggested that, when available, patients be enrolled in properly designed clinical trials assessing the value of diffusion tensor imaging in improving the safety of patients with newly diagnosed glioblastoma undergoing surgery. Neuropathology Question What new pathology techniques and measurement of biomarkers in tumor tissue can be used to provide improved diagnostic ability, and determination of therapeutic responsiveness and prognosis for patients with newly diagnosed glioblastomas? Recommendations Level II: Assessment of tumor MGMT promoter methylation status is recommended as a significant predictor of a longer progression free survival and overall survival in patients with newly diagnosed with glioblastoma. Level

关键词： SARS-CoV-2   COVID-19   Pandemic   Neurological consultation   Encephalopathy   Stroke   Encephalitis   Seizures  

摘要： Background COVID-19 disease affects the nervous system and led to an increase in neurological consults for patients at admission and through the period of hospitalization during the peak of the pandemic. Methods Patients with clinical and laboratory diagnosis of COVID-19 that required a neurologic consultation or those who presented with neurological problems on admission that led to a diagnosis of SARS-CoV-2 infection during a 2-month period at the peak of the pandemic were included in this study. Demographic and clinical variables were analyzed. Results Thirty-five patients were included. The presenting neurologic manifestations on admission led to the diagnosis of COVID-19 in 14 patients (40%). The most common reasons for consultation during the hospitalization period were stroke (11), encephalopathy (7), seizures (6), and neuropathies (5) followed by a miscellaneous of syncope (2), migraine (1), anosmia (1), critical illness myopathy (1), and exacerbation of residual dysarthria (1). The most common neurological disturbances were associated with severe disease except for neuropathies. Patients with encephalopathies and seizures had markedly increased D-dimer and ferritin values, even higher than stroke patients. RT-PCR was performed in 8 CSF samples and was negative in all of them. Conclusion Neurological disturbances represent a significant and severe burden in COVID-19 patients, and they can be the presenting condition that leads to the diagnosis of the viral infection in a high percentage of patients. Evidence of direct viral mechanisms was scarce, but the pathogenesis of the diverse manifestations remains enigmatic.

关键词： adaptive functioning   brain tumor   neuropsychology   processing speed   young adult  

摘要： Purpose Brain tumor (BT) survivors are at risk for difficulties with adaptive functioning (AF). Recent work has associated neurological risk with poorer AF outcomes using the Neurological Predictor Scale (NPS), a quantification of neurological risk factors. Survivors also have poorer attention, processing speed, and working memory, which are all important for AF. The current study examined whether these cognitive constructs explain the relationship between the NPS and AF in survivors. Methods Ninety-five adult BT survivors and 135 healthy controls were recruited from the Atlanta area. The Oral Symbol Digits Modalities test was used to measure processing speed, Digit Span Backward assessed working memory, and Digit Span Forward measured attention. Informants completed the Scales of Independent Behavior (SIB-R) to measure AF. Group differences and correlations were assessed, and the PROCESS macro for SPSS tested indirect effects. Results Survivors were significantly lower on AF and cognitive measures compared with controls. Attention span and processing speed had significant indirect effects in relationship between NPS and AF individually, but processing speed was the only variable with a significant indirect effect when all cognitive variables were included in the model. The NPS and processing speed together account for approximately 39% of variance in AF outcomes. Conclusions BT survivors in our sample have lower AF than controls, and processing speed appears to be particularly important in explaining the relationship between neurological risk and AF. In the future, the development of interventions aimed at increasing young adult independence should target both cognitive processing speed and AF skills.

关键词： Baicalin   Inflammatory   Immunomodulatory   Cerebrovascular   Neurological disorders  

摘要： Inflammatory responses play an extraordinary role in the pathogenesis of cerebrovascular and neurological disorders. Baicalin is one of the important flavonoids, which is extracted from Scutellaria baicalensis Georgi. Recently, numerous in vivo and in vitro studies have shown that baicalin has salutary effects for anti-inflammatory and immunomodulatory and has been demonstrated to exert beneficial therapeutic properties in cerebrovascular and neurological diseases. In this review, we aim to discuss that baicalin exerts anti-inflammatory effects through multiple pathways and targets, thus affecting the production of a variety of inflammatory cytokines and neuroprotective process of neurological diseases;furthermore, the related targets of the anti-inflammatory effects of baicalin were analyzed via using the tools of network pharmacology, to provide theoretical basis and innovative ideas for the future clinical application of baicalin.

摘要： A growing need exists for reliable in-vivo measurement of neuroinflammation to better characterise the inflammatory processes underlying various diseases and to inform the development of novel therapeutics that target deleterious filial activity. PET is well suited to quantify neuroinflammation and has the potential to discriminate components of the neuroimmune response. However, there are several obstacles to the reliable quantification of neuroinflammation by PET imaging. Despite these challenges, PET studies have consistently identified associations between neuroimmune responses and pathophysiology in brain disorders such as Alzheimer's disease. Tissue studies have also begun to clarify the meaning of changes in PET signal in some diseases. Furthermore, although PET imaging of neuroinflammation does not have an established clinical application, novel targets are under investigation and a small but growing number of studies have suggested that this imaging modality could have a role in drug development. Future studies are needed to further improve our knowledge of the cellular mechanisms that underlie changes in PET signal, how immune response contributes to neurological disease, and how it might be therapeutically modified.

关键词： Crocin   Neuro-protective   Flavonoids   Antioxidant   Antiapoptotic   Anti-Neuroinflammation  

摘要： Neurological sicknesses are serious, multifactorial, debilitating disorders that may cause neurodegeneration. Neuroprotection is the protection of the structure and capacity of neurons from affronts emerging from cell injuries instigated by an assortment of specialists or neurodegenerative diseases. Various neurodegenerative diseases, including Alzheimer's, Parkinson's, and epilepsy, afflict many people worldwide, with increasing age representing the leading risk factor. Crocin is a natural carotenoid compound which was found to have therapeutic potentials in the management of the neurological disease. In this review, we focused on the restorative capabilities of Crocin as a neuroprotective agent. The general neuroprotective impact and the various conceivable basic components identified with Crocin have been examined. In light of the substantial proof indicating the neuro-pharmacological viability of Crocin to different exploratory standards, it is concluded that Crocin exerts direct antioxidant, antiapoptotic and anti-inflammatory activities by multiple signaling pathways. Besides, Crocin was found to elevate dopamine level in the brain during the experimental model of Parkinson's disease. Thus, this compound has been demonstrated to be a promising option for the treatment of neurodegenerative diseases, with few adverse effects. It ought to be further considered as a potential contender for neurotherapeutics, concentrating on the mechanistic and clinical evidence for its effects.

关键词： Cannabidiol   Efficacy   Ethicality   Neurologic disorders  

摘要： Cannabidiol (CBD), which is nonintoxicating pharmacologically relevant constituents ofCannabis, demonstrates several beneficial effects. It has been found to have antioxidative, anti-inflammatory, and neuroprotective effects. As the medicinal use of CBD is gaining popularity for treatment of various disorders, the recent flare-up of largely unproven and unregulated cannabis-based preparations on medical therapeutics may have its greatest impact in the field of neurology. Currently, as lot of clinical trials are underway, CBD demonstrates remarkable potential to become a supplemental therapy in various neurological conditions. It has shown promise in the treatment of neurological disorders such as anxiety, chronic pain, trigeminal neuralgia, epilepsy, and essential tremors as well as psychiatric disorders. While recent FDA-approved prescription drugs have demonstrated safety, efficacy, and consistency enough for regulatory approval in spasticity in multiple sclerosis (MS) and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges still remain. In the current review, the authors have shed light on the application of CBD in the management and treatment of various neurological disorders.

关键词： Complex V   Phenotype   MT-ATP6   Blue native PAGE   Respirometry  

摘要： Diagnosing complex V deficiencies caused by new variants in mitochondrial DNA is challenging due to the rarity, phenotypic diversity, and limited functional assessments. We describe a child with the m.9032T > C variant in MT-ATP6 encoding p.(Leu169Pro), with primary presentation of microcephaly, ataxia, hearing loss, and lactic acidosis. Functional studies reveal abnormal fragment F1 of complex V on blue native gel electrophoresis. Respirometry showed excessively tight coupling through complex V depressing oxygen consumption upon ADP stimulation and an excessive increase following uncoupling, in the presence of upregulation of mitochondrial biogenesis. These data add evidence about pathogenicity and functional impact of this variant.

关键词： Stroke   Basilar artery occlusion   Endovascular therapy   Outcomes  

摘要： Background and purpose: We hypothesized that the relationships between treatments and outcomes in acute basilar artery occlusion (BAO) are different, depending on the severity of initial neurological deficits. Methods: Of 2420 ischemic stroke patients with large vessel occlusion in a prospective, multicenter registry in Japan, patients with acute BAO were enrolled. Subjects were divided into two severity groups according to the baseline NIH Stroke Scale score: severe (>= 10) and mild (<10) groups. The primary effectiveness outcome was favorable outcome, defined as modified Rankin Scale score 0-3 at 3 months. Safety outcomes included any intracranial hemorrhage (ICH) within 72 h. Outcomes in each group were compared between patients who received endovascular therapy (EVT) and those with standard medical treatment (SMT). Results: In this study, 167 patients (52 female;median age 75 years) were analyzed. The favorable outcome was seen in 93 patients (56%) overall. In the severe group (n = 128), the proportion of favorable outcome was higher in patients who received EVT (60/111, 54%) than those with SMT (2/17, 12%, P < 0.01). In the mild group (n = 39), the rates of favorable outcome were comparable between the EVT (13/18, 72%) and SMT patients (18/21, 86%, P = 0.43). No significant differences in the rates of any ICH were seen among any groups. Conclusions: In acute BAO stroke with severe neurological deficit, independent ambulation was more frequently seen in patients who received EVT than those with SMT. Patients with mild neurological deficits showed similar rates of independent ambulation between the two treatment selections.