Epidemiology of Cerebrovascular Disease Among Chinese Canadian Adults With Type 2 Diabetes.

BACKGROUND: First-generation Chinese Canadians have usually maintained different lifestyles before immigration to North America, and the question of whether Chinese Canadians with type 2 diabetes have a different stroke profile than that of non-Chinese Canadians remains unanswered. OBJECTIVES: To determine whether 1) Chinese Canadians who have had a stroke within the last 15 years are more likely to have diabetes than non-Chinese Canadians and 2) to explore differences in stroke profiles between the 2 cohorts. METHODS: Age- and sex-matched Chinese Canadians (n=70) and non-Chinese Canadians (n=107) were compared on the basis of stroke type, age at stroke onset, stroke etiology and common risk factors. Classifications for disease were done according to professional guidelines. Statistical analysis was done with Student t test and odds ratios to confirm differences between groups. RESULTS: Chinese Canadians with stroke had a higher frequency of diabetes mellitus than non-Chinese Canadians. Chinese Canadians with diabetes were more likely to have small vessel disease, specifically lacunar stroke. Chinese Canadians at high risk for stroke were more likely to have a poor prognosis than non-Chinese Canadians, with near significance. CONCLUSION: Chinese Canadians with diabetes who had ischemic strokes were especially susceptible to intracranial small vessel disease compared with non-Chinese Canadians. These results signify that risk factor prevalence and stroke types differ considerably between Chinese Canadians and non-Chinese Canadians residing in Toronto, warranting further study.

Lesions causing freezing of gait localize to a cerebellar functional network.

OBJECTIVE: Freezing of gait is a disabling symptom in Parkinson disease and related disorders, but the brain regions involved in symptom generation remain unclear. Here we analyze brain lesions causing acute onset freezing of gait to identify regions causally involved in symptom generation. METHODS: Fourteen cases of lesion-induced freezing of gait were identified from the literature, and lesions were mapped to a common brain atlas. Because lesion-induced symptoms can come from sites connected to the lesion location, not just the lesion location itself, we also identified brain regions functionally connected to each lesion location. This technique, termed lesion network mapping, has been recently shown to identify regions involved in symptom generation across a variety of lesion-induced disorders. RESULTS: Lesion location was heterogeneous, and no single region could be considered necessary for symptom generation. However, > 90% (13 of 14) of lesions were functionally connected to a focal area in the dorsal medial cerebellum. This cerebellar area overlapped previously recognized regions that are activated by locomotor tasks, termed the cerebellar locomotor region. Connectivity to this region was specific to lesions causing freezing of gait compared to lesions causing other movement disorders (hemichorea or asterixis). INTERPRETATION: Lesions causing freezing of gait are located within a common functional network characterized by connectivity to the cerebellar locomotor region. These results based on causal brain lesions complement prior neuroimaging studies in Parkinson disease patients, advancing our understanding of the brain regions involved in freezing of gait. ANN NEUROL 2017;81:129-141.

Pharmacologic inhibition of reactive gliosis blocks TNF-α-mediated neuronal apoptosis.

Reactive gliosis is an early pathological feature common to most neurodegenerative diseases, yet its regulation and impact remain poorly understood. Normally astrocytes maintain a critical homeostatic balance. After stress or injury they undergo rapid parainflammatory activation, characterized by hypertrophy, and increased polymerization of type III intermediate filaments (IFs), particularly glial fibrillary acidic protein and vimentin. However, the consequences of IF dynamics in the adult CNS remains unclear, and no pharmacologic tools have been available to target this mechanism in vivo. The mammalian retina is an accessible model to study the regulation of astrocyte stress responses, and their influence on retinal neuronal homeostasis. In particular, our work and others have implicated p38 mitogen-activated protein kinase (MAPK) signaling as a key regulator of glutamate recycling, antioxidant activity and cytokine secretion by astrocytes and related Müller glia, with potent influences on neighboring neurons. Here we report experiments with the small molecule inhibitor, withaferin A (WFA), to specifically block type III IF dynamics in vivo. WFA was administered in a model of metabolic retinal injury induced by kainic acid, and in combination with a recent model of debridement-induced astrocyte reactivity. We show that WFA specifically targets IFs and reduces astrocyte and Müller glial reactivity in vivo. Inhibition of glial IF polymerization blocked p38 MAPK-dependent secretion of TNF-α, resulting in markedly reduced neuronal apoptosis. To our knowledge this is the first study to demonstrate that pharmacologic inhibition of IF dynamics in reactive glia protects neurons in vivo.