Post-acute delivery of α5-GABAA antagonist, S 44819, improves functional recovery in juvenile rats following stroke

被引：1

作者：

Lebrun, Florent ^{[1
,2
]}

Violle, Nicolas ^{[1
]}

Letourneur, Annelise ^{[1
]}

Muller, Christophe ^{[1
]}

Fischer, Nicolas ^{[1
]}

Levilly, Anthony ^{[3
]}

Orset, Cyrille ^{[2
,3
]}

Sors, Aurore ^{[4
]}

Vivien, Denis ^{[2
,5
]}

机构：

[1] STROK LLIANCE, ETAP Lab, 13 Rue Bois Champelle, F-54500 Vandoeuvre Les Nancy, France

[2] UNICAEN, Physiopathol & Imaging Neurol Disorders PhIND, Inst Blood & Brain Caen Normandie BB C, Normandie Univ,GIP Cyceron,INSERM,UMR S U1237, Caen, France

[3] Univ Caen Basse Normandie, Ctr Univ Ressources Biol Curb, ESRP European Stroke Res Platform, Caen, France

[4] Inst Rech Int Servier, Suresnes, France

[5] CHU Caen Normandie, Dept Clin Res, Caen, France

来源：

EXPERIMENTAL NEUROLOGY | 2022年 / 347卷

关键词：

Animal model; Behavioural tests; GABA; Recovery; Stroke; FOCAL CEREBRAL-ISCHEMIA; ARTERY OCCLUSION; TONIC INHIBITION; INTRALUMINAL SUTURE; MATURATION; HYPERACTIVITY; REDUCTION; RECEPTORS; DEFICITS; S44819;

D O I：

10.1016/j.expneurol.2021.113881

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Hypo-excitability was reported in the peri-infarct tissue following stroke, an effect counteracted by a blockage of alpha 5-GABAA receptors in adult rodents. Our present study aims to evaluate the effect of a selective alpha 5-GABAA receptor antagonist, S 44819, in stroke in juvenile animals. We have set up and characterized an original model of transient ischemic stroke in 28 day-old Sprague-Dawley rats (45-min occlusion of the middle cerebral artery by intraluminal suture). In this model, S 44819 (1, 3 and 10 mg/kg, b.i.d) was orally administered from day 3 to day 16 after stroke onset. Sensorimotor recovery was assessed on day 1, day 9 and day 16 after stroke onset. Results show that rats treated with S 44819 at the doses of 3 and 10 mg/kg displayed a significant improvement of the neurological deficits (neuroscore) on day 9 and day 16, when compared with animals treated with vehicle. Grip test data analysis reveals that rats treated with S 44819 at the dose of 3 mg/kg displayed a better recovery on day 9 and day 16. These results are in agreement with those previously observed in adult rats, demonstrating that targeting alpha 5-GABAA receptors improves neurological recovery after stroke in juvenile rats.

引用

页数：9

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