Plasminogen activator inhibitor type 1 derived peptide, EEIIMD, diminishes cortical infarct but fails to improve neurological function in aged rats following middle cerebral artery occlusion.
Age is a primary risk factor in stroke that is often overlooked in animal studies. We contend that using aged animals yields insight into aspects of stroke injury and recovery that are masked, or not elicited, in younger animals. In this study, we examined effects of co-administration of a plasminogen activator inhibitor type 1 derived peptide, Glu-Glu-Iso-Iso-Met-Asp (EEIIMD), with tissue plasminogen activator (tPA) on infarct volume and functional outcome in aged rats following a transient middle cerebral artery occlusion. Results of our study showed aged (18-20 months) rats treated with EEIIMD along with tPA had reduced cortical infarction volume. However, aged rats showed no improvement in total infarction volume, edema formation, or functional outcome as compared to aged rats administered only tPA. Young adult rats (3-4 months) treated with EEIIMD showed significant improvement in cortical and total infarction volumes, edema formation, and functional outcome. Striatal infarction volume was unaffected by EEIIMD treatment in both young adult and aged rats. These findings emphasize that physiological differences exist between young adult and aged rats and suggest that taking aging processes into account when assessing stroke may improve our ability to discern which therapeutics can be translated from bench to bedside.
Tan
Zhenjun
Z
Department of Neurosurgery, West Virginia University, Morgantown, WV 26506, USA.
Li
Xinlan
X
Kelly
Kimberly A
KA
Rosen
Charles L
CL
Huber
Jason D
JD
D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004487:Edema / Q000188:drug therapy; D005260:Female; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009842:Oligopeptides / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D012720:Severity of Illness Index; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
D018696:Neuroprotective Agents; D009842:Oligopeptides; C513663:glutamyl-glutamyl-isoleucyl-isoleucyl-methionyl-aspartic acid; D010959:Tissue Plasminogen Activator