Simultaneous knockdown of TLR2 and TLR4 after focal cerebral ischemia facilitates the post‐stroke neurological recovery in rats

Abstract

Ischemic stroke is the primary reason for serious long‐term disability. Our recent studies demonstrated that the suppression of toll‐like receptors (TLRs) 2 and 4 alone or in combination attenuated the post‐ischemic inflammation and brain damage. The purpose of this study is to investigate the effect of the simultaneous knockdown of both TLR2 and TLR4 on post‐stroke neurological recovery in young adult male rats. Transient focal cerebral ischemia was induced to male Sprague‐Dawley rats by middle cerebral artery occlusion (MCAO) procedure. A silicone rubber‐coated monofilament suture was introduced into the internal carotid artery via the external and common carotid arteries and pushed until it reaches the origin of the middle cerebral artery followed by removal of the monofilament after 2 hours to initiate reperfusion. Appropriate cohorts of rats were treated with a nanoparticle formulations of TLR2shRNA (T2sh) and TLR4shRNA (T4sh) expressing plasmids (1mg/kg each of T2sh and T4sh) or scrambled sequence inserted vector (SVsh; vehicle) expressing plasmids (2 mg/kg) intravenously via tail vein immediately after reperfusion. The rats from both the cohorts were subjected to various standard neurological tests such as modified neurological severity scores (mNSS), modified adhesive removal (sticky‐tape), beam walking and accelerating rotarod performance before MCAO procedure and at days 1, 3, 5, 7, and 14 after reperfusion. The sensory and motor functions of vehicle treated stroke‐induced rats were markedly impaired when tested at 1d reperfusion followed by a gradual improvement over 14 days. Prevention of the post‐ischemic induction of TLR2 and TLR4 attenuated the degree of neurological impairment and facilitated the magnitude of functional recovery. Therefore, we conclude that the post‐stroke induction of TLR2 and TLR4 in rat ischemic brain contributes to neurological deficits.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.