Protective Role of Levetiracetam Against Cognitive Impairment And Brain White Matter Damage in Mouse prolonged Cerebral Hypoperfusion

Publication date: Available online 11 July 2019Source: NeuroscienceAuthor(s): Toshiki Inaba, Nobukazu Miyamoto, Kenichiro Hira, Yuji Ueno, Kazuo Yamashiro, Masao Watanabe, Yoshiaki Shimada, Nobutaka Hattori, Takao UrabeAbstractWhite matter lesions due to cerebral hypoperfusion may be an important pathophysiology in vascular dementia and stroke, although the inherent mechanisms remain to be fully elucidated. The present study, using a mouse model of chronic cerebral hypoperfusion, examined the white matter protective effects of levetiracetam, an anticonvulsant, via the signaling cascade from the activation of cAMP-responsive element binding protein (CREB) phosphorylation. Mice underwent bilateral common carotid artery stenosis (BCAS), and were separated into the levetiracetam group (injected once only after BCAS [LEV1] or injected on three consecutive days [LEV3]), the vehicle group, or the anti-epileptic drugs with different action mechanisms phenytoin group (PHT3; injected on three consecutive days with the same condition as in LEV3). Cerebral blood flow analysis, Y-maze spontaneous alternation test, novel object recognition test, immunohistochemical and Western blot analyses, and protein kinase A assay were performed after BCAS. In the LEV3 group, SV2A expression was markedly increased, which preserved learning and memory after BCAS. Moreover, as the protein kinase A level was significantly increased, pCREB expression was also increased. The activation of microglia and astr...

Source: Neuroscience - July 12, 2019 Category: Neuroscience Source Type: research