AMPA receptor antagonist perampanel ameliorates post-stroke functional and cognitive impairments

Publication date: Available online 5 July 2018Source: NeuroscienceAuthor(s): Masataka Nakajima, Satoshi Suda, Kota Sowa, Yuki Sakamoto, Chikako Nito, Yasuhiro Nishiyama, Junya Aoki, Masayuki Ueda, Shoji Yokobori, Marina Yamada, Hiroyuki Yokota, Takashi Okada, Kazumi KimuraAbstractPerampanel (PER), a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonist, clinically used for seizure control, has been reported to exert neuroprotective effects in experimental models of neurodegenerative diseases. However, few studies have investigated the therapeutic effects of PER in brain injury including stroke. Our aim was to investigate the neuroprotective potential of PER using a rat transient middle cerebral artery occlusion (MCAO) model. Sprague-Dawley rats underwent 90-minute MCAO followed by intraperitoneal PER administration at a dose of 1.5 mg/kg. Infarct volumes, neurological deficits, and immunological analyses were performed at 7 days after MCAO. PER significantly reduced infarct volumes (p < 0.05) and improved motor function (p < 0.05) compared with vehicle. Immunological analysis showed that PER significantly inhibited microglial activation, pro-inflammatory cytokine expression, and oxidative stress compared with vehicle. Moreover, PER suppressed neurodegeneration in the cortical ischemic boundary zone, via downregulation of Bcl-2 associated x and upregulation of Bcl-extra-large with Akt activation. In addition, post-stroke secondary neuron...
Source: Neuroscience - Category: Neuroscience Source Type: research