关键词： Animal model   cerebral blood flow   embolic MCAO   laser speckle   thrombolytic therapy  

摘要： The embolic middle cerebral artery occlusion (eMCAO) model mimics ischemic stroke due to large vessel occlusion in humans and is amenable to thrombolytic therapy with rtPA. However, two major obstacles, the difficulty of the eMCAO surgery and unpredictable occurrence of clot autolysis, had impeded its application in mice. In this study, we modified catheters to produce suitable fibrin-rich embolus and optimized the eMCAO model using cerebral blood flow (CBF) monitored by both laser Doppler flowmetry (LDF) and 2D laser speckle contrast imaging (LSCI) to confirm occlusion of MCA. The results showed that longer embolus resulted in higher mortality. There was a compensatory increase in MCA territory perfusion after eMCAO associated with decreased infarct volume;however, this was only partly dependent on recanalization as clot autolysis was only observed in similar to 30% of mice. Cortical CBF monitoring with LSCI showed that the size of peri-core area at 3 h displayed the best correlation with infarct volume that is attributed to compensatory collateral blood flow. The peri-core area best predicted functional outcome after eMCAO. In summary, we developed a reliable eMCAO mouse model that better mimics embolic ischemic stroke in humans, which will increase the potential for successful translation of stroke neuroprotective therapies.

关键词： access to care   headache centers   headache neurology   headache treatment   multidisciplinary treatment   qualitative research  

摘要： Background and Objective Comprehensive headache care involves numerous specialties and components that have not been well documented or standardized. This study aimed to elicit best practices and characterize important elements of care to be provided in multidisciplinary headache centers. Methods Qualitative, semi-structured telephone interviews with a purposive sample of headache neurology specialists from across the US, using open-ended questions. Interviews were recorded, transcribed, and coded. Coded data were further analyzed using immersion/crystallization techniques for final interpretation. Results Mean years providing headache care was 17.7 (SD = 10.6). Twelve of the 13 participants held United Council for Neurologic Subspecialties headache certification. Six described their practice site as providing multidisciplinary headache care. Participants explained most of their patients had seen multiple doctors over many years, and had tried numerous unsuccessful treatments. They noted patients with chronic headache frequently present with comorbidities and become stigmatized. All participants asserted successful care depends on taking time to talk with and listen to patients, gain understanding, and earn trust. All participants believed multidisciplinary care is essential within a comprehensive headache center, along with staffing enough headache specialists, implementing detailed headache intake and follow-up protocols, and providing the newest medications, neuromodulation devices, botulinum toxin injections, monoclonal antibodies, nerve blocks and infusions, and treatment from a health psychologist. Other essential services for a headache center are other behavioral health practitioners providing cognitive behavioral therapy, mindfulness, biofeedback and pain management;and autonomic neurology, neuropsychology, vestibular audiology, sleep medicine, physical therapy, occupational therapy, exercise physiology, speech therapy, nutrition, complementary integrative

摘要： This commentary is on the original article by Abuga et al. on pages 347–356 of this issue.

关键词： Dengue   Neurological manifestations   Arbovirus   Serotype   Infection   Hypokalemic paralysis  

摘要： Introduction Neurological manifestation of dengue virus infection is a rare entity. Serotypes commonly associated with neurological manifestation are DENV-2 and DENV-3. We plan to detect the serotypes related to the neurological presentation in dengue infection and its correlation with different neurological complications and outcome. Methods In this case-control study, consecutive dengue cases with different neurological manifestations were enrolled along with age and sex-matched controls (dengue patients without neurological complication). Serotyping using RT-PCR of samples of cases and controls were done. Level of correlation was analyzed with various parameters and outcomes. Results In cases out of 33 samples, 6 sample serotypes were detected, which were composed of DENV-1 (n = 2) and DENV-2 (n = 4). In controls, DENV-1 (n = 5), DENV-2 (n = 6), and DENV-3 (n = 3) were detected. When statistically correlated, no significant association was found in cases and controls with dengue virus serotype. The frequency of serotype 2 was higher in hypokalemic paralysis cases than non-hypokalemic paralysis cases and the difference was significant (p < 0.05). The outcome was good (mRS < 3) in all the cases where serotypes were detected, but on statistical correlation, it was not found significant (p > 0.05). Conclusion DENV-1 and DENV-2 are associated with neurological manifestation of dengue infection, which is different from the existing literature, where DENV-2 and DENV-3 are reported. The detection of DENV serotype will help in predicting and best management of neurological complication. The serotype 2 of dengue virus is more commonly associated with dengue-associated hypokalemic paralysis than other neurological complication (p < 0.05). There is no significant association of serotypes with outcome or mortality.

关键词： Neurology   Neurosciences   Neuroradiology  

关键词： Positron emission tomography (PET)   Reactive astrocytes   Monoamine oxidases-B (MAO-B)   Alzheimer's disease (AD)   Parkinson's disease (PD)   Amyotrophic lateral sclerosis (ALS)   Multiple sclerosis (MS)  

摘要： The reactive astrocytes manifest molecular, structural, and functional remodeling in injury, infection, or diseases of the CNS, which play a critical role in the pathological mechanism of neurological diseases. A growing need exists for dependable approach to better characterize the activation of astrocyte in vivo. As an advanced molecular imaging technology, positron emission tomography (PET) has the potential for visualizing biological activities at the cellular levels. In the review, we summarized the PET visualization strategies for reactive astrocytes and discussed the applications of astrocyte PET imaging in neurological diseases. Future studies are needed to pay more attention to the development of specific imaging agents for astrocytes and further improve our exploration of reactive astrocytes in various diseases.

摘要： The blood-brain barrier (BBB) protects the central nervous system (CNS) from harmful blood-borne factors. Although BBB dysfunction is a hallmark of several neurological disorders, therapies to restore BBB function are lacking. An attractive strategy is to repurpose developmental BBB regulators, such as Wnt7a, into BBB-protective agents. However, safe therapeutic use of Wnt ligands is complicated by their pleiotropic Frizzled signaling activities. Taking advantage of the Wnt7a/b-specific Gpr124/Reck co-receptor complex, we genetically engineered Wnt7a ligands into BBB-specific Wnt activators. In a "hit-and-run" adeno-associated virus-assisted CNS gene delivery setting, these new Gpr124/Reck-specific agonists protected BBB function, thereby mitigating glioblastoma expansion and ischemic stroke infarction. This work reveals that the signaling specificity of Wnt ligands is adjustable and defines a modality to treat CNS disorders by normalizing the BBB.