alpha-synuclein and Infarction--Middle-Cerebral-Artery

The etiology of Parkinson's disease is poorly understood and is most commonly associated with advancing age, genetic predisposition, or environmental toxins. Epidemiological findings suggest that patients have a higher risk of developing Parkinson's disease after ischemic stroke, but this potential causality lacks mechanistic evidence. We investigated the long-term effects of ischemic stroke on pathogenesis in hemizygous TgM83 mice, which express human α-synuclein with the familial A53T mutation without developing any neuropathology or signs of neurologic disease for more than 600 days. We induced transient focal ischemia by middle cerebral artery occlusion in 2-month-old TgM83

Topics: alpha-Synuclein; Animals; Disease Models, Animal; Dopaminergic Neurons; Humans; Infarction, Middle Cerebral Artery; Inflammation; Ischemic Stroke; Mice; Mice, Transgenic; Parkinson Disease

Topics: alpha-Synuclein; Animals; Brain; Brain Ischemia; Down-Regulation; Endosomes; Infarction, Middle Cerebral Artery; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Models, Animal; Nedd4 Ubiquitin Protein Ligases; Neurodegenerative Diseases; Neurons; Neuroprotection; Parkinson Disease; Protein Aggregation, Pathological; Protein Processing, Post-Translational; Stroke; Ubiquitin-Protein Ligases; Ubiquitination; Up-Regulation

Increased expression of α-Syn (α-Synuclein) is known to mediate secondary brain damage after stroke. We presently studied if α-Syn knockdown can protect ischemic brain irrespective of sex and age.. Adult and aged male and female mice were subjected to transient middle cerebral artery occlusion. α-Syn small interfering RNA (siRNA) was administered intravenous at 30 minutes or 3 hour reperfusion. Poststroke motor deficits were evaluated between day 1 and 7 and infarct volume was measured at day 7 of reperfusion.. α-Syn knockdown significantly decreased poststroke brain damage and improved poststroke motor function recovery in adult and aged mice of both sexes. However, the window of therapeutic opportunity for α-Syn siRNA is very limited.. α-Syn plays a critical role in ischemic brain damage and preventing α-Syn protein expression early after stroke minimizes poststroke brain damage leading to better functional outcomes irrespective of age and sex.

Topics: Age Factors; alpha-Synuclein; Animals; Brain; Disease Models, Animal; Female; Gene Knockdown Techniques; Infarction, Middle Cerebral Artery; Male; Mice; Recovery of Function; RNA, Small Interfering; Sex Factors; Stroke

Piper nigrum L. and Piper longum L. consist a classic formula in traditional Chinese Hui medicine and are widely used in treatment of stroke. To examine the therapeutic effect of neuron injury after apoplexy, we used a permanent middle cerebral artery occlusion model in rats to investigate the effects of dichloromethane fraction (DF) of Piper nigrum L. and Piper longum L.. DF alleviated neurological deficits and markedly prevented ischemia-induced cellular damage. Immunohistochemical micrographs revealed that PSD-95 and syn-I proteins increased, and α-syn presented reduced expression in brain samples from the sham group. Western blot analyses revealed that the model group exhibited a noticeable reduction in PSD-95, p-CaMK II, CaM, and NR2B. The DF-treated model group exhibited increased PSD-95, p-CaMK II, CaM, and NR2B. UPLC-Q-TOF/MS analysis revealed eight main components of DF, of which piperine accounted for the largest proportion.

Topics: alpha-Synuclein; Animals; Behavior, Animal; Brain; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calmodulin; Disease Models, Animal; Disks Large Homolog 4 Protein; Infarction, Middle Cerebral Artery; Male; Methylene Chloride; Motor Activity; Neurons; Neuroprotective Agents; Phosphorylation; Piper; Piper nigrum; Plant Extracts; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Solvents; Synapsins