Acute functional effects of cyclosporine-A and methylprednisolone treatment in adult rats exposed to transient ischemic stroke.
The present study examined the neuroprotective effects of immunosuppressant cyclosporine-A (CsA) and anti-inflammatory methylprednisolone (MP) in a stroke model. Adult Sprague-Dawley rats were initially subjected to transient middle cerebral artery occlusion (MCAo) then randomly assigned to one of the following treatment conditions: low dose CsA, MP, low dose CsA plus MP, high dose CsA, or vehicle. Ischemic animals that received low dose CsA, MP or vehicle exhibited significant cognitive impairments, as revealed by passive avoidance and Morris water maze tasks, at days 1-3 after stroke. In contrast, ischemic animals that received high dose CsA exhibited near normal cognitive performance throughout the test period. Ischemic animals that received low dose CsA plus MP also showed significantly less cognitive deficits but such attenuation of stroke-induced behavioral impairments was only consistently reflected in the passive avoidance task, while performance in the Morris water maze task deteriorated over time. Histological analysis at 3 days post-stroke revealed that only those ischemic animals treated with high dose CsA had significantly reduced cerebral infarcts. These observations suggest that despite overt cerebral damage, alterations in simple, but not complex, cognitive tasks produced by MCAo could be ameliorated by low dose CsA when combined with MP.
Borlongan
Cesario V
CV
Department of Neurology, Medical College of Georgia, Augusta VAMC, GA 30912, USA. cborlongan@mail.mcg.edu
Yu
Guolong
G
Matsukawa
Noriyuki
N
Xu
Lin
L
Hess
David C
DC
Sanberg
Paul R
PR
Wang
Yun
Y
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000473:pathology; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008775:Methylprednisolone / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents; D016572:Cyclosporine; D008775:Methylprednisolone