Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1503-1512 |
| Number of pages | 10 |
| Journal | Life sciences |
| Volume | 76 |
| Issue number | 13 |
| DOIs | |
| State | Published - Feb 11 2005 |
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Keywords
- Brain infarct
- Cerebral ischemia
- Cognitive tasks
- Immunosuppression
- Inflammation
- Neuroprotection
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)
Cite this
Acute functional effects of cyclosporine-A and methylprednisolone treatment in adult rats exposed to transient ischemic stroke. / Borlongan, Cesario V.; Yu, Guolong; Matsukawa, Noriyuki; Xu, Lin; Hess, David C; Sanberg, Paul R.; Wang, Yun.
In: Life sciences, Vol. 76, No. 13, 11.02.2005, p. 1503-1512.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Acute functional effects of cyclosporine-A and methylprednisolone treatment in adult rats exposed to transient ischemic stroke
AU - Borlongan, Cesario V.
AU - Yu, Guolong
AU - Matsukawa, Noriyuki
AU - Xu, Lin
AU - Hess, David C
AU - Sanberg, Paul R.
AU - Wang, Yun
PY - 2005/2/11
Y1 - 2005/2/11
N2 - 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.
AB - 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.
KW - Brain infarct
KW - Cerebral ischemia
KW - Cognitive tasks
KW - Immunosuppression
KW - Inflammation
KW - Neuroprotection
UR - http://www.scopus.com/inward/record.url?scp=12844262878&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12844262878&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2004.09.022
DO - 10.1016/j.lfs.2004.09.022
M3 - Article
VL - 76
SP - 1503
EP - 1512
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
IS - 13
ER -