A Comparative Study of Neuroprotective Effect of Single and Combined Blockade of AT1 Receptor and PARP-1 in Focal Cerebral Ischaemia in Rat

Author:

Singh Neetu,Sharma Gaurav,Singh Nilendra,Hanif Kashif

Abstract

Background Cerebral ischaemia results in enhanced expression of type 1 angiotensin receptor and oxidative stress. Free radicals due to oxidative stress lead to excessive DNA damage causing overactivation of poly (ADP-ribose) polymerase-1 resulting in neuronal death. Activation of both type 1 angiotensin receptors and poly (ADP-ribose) polymerase-1 following cerebral ischaemia takes place simultaneously, but until now, no study has explored the effect of combined blockade of both angiotensin type 1 angiotensin receptor and poly (ADP-ribose) polymerase-1 in cerebral ischaemia. Aim Our purpose was to compare the effect of single and combined treatment with angiotensin type 1 angiotensin receptor blocker, candesartan, and the poly (ADP-ribose) polymerase-1 inhibitor, 1, 5 isoquinolinediol, on brain damage and oxidative stress in transient focal cerebral ischaemia in rats. Method Transient focal cerebral ischaemia was induced in Sprague-Dawley rats by an intraluminal technique for two-hours following 48 h of reperfusion. Candesartan (0·05 mg/kg) was administered just after initiation of ischaemia followed by a repeat administration at 24 h while 1, 5 isoquinolinediol (0·1 mg/kg) was given one-hour after of ischaemia. After 24 h of reperfusion, neurological deficit was evaluated in the different treatment groups. After 48 h of reperfusion, the rats were sacrificed and the brain was isolated. Ischaemic brain damage by 2,3,5 triphenyl tetrazolium chloride staining, oxidative stress markers, and levels of reactive oxygen species were determined biochemically. Result Single treatment with candesartan and 1, 5 isoquinolinediol significantly reduced neurological deficit, infarct, and oedema volume as compared to ischaemic control and different vehicle groups for each of the drugs. However, treatment with candesartan + 1, 5 isoquinolinediol offered greater reduction in neurological deficit, cerebral infarct volume, and oedema as compared to single-drug treatments. Furthermore, treatment with candesartan + 1, 5 isoquinolinediol significantly decreased oxidative stress as compared to single treatments with each drug. Conclusion The study suggests that blockade of either type 1 angiotensin receptor or poly (ADP-ribose) polymerase-1 alone provides neuroprotection, but the better result was achieved when both type 1 angiotensin receptor and poly (ADP-ribose) polymerase-1 were blocked together by the combined use of their pharmacological inhibitor in transient cerebral ischaemia in rat.

Publisher

SAGE Publications

Subject

Neurology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3