COG1410, an apolipoprotein E-based peptide, improves cognitive performance and reduces cortical loss following moderate fluid percussion injury in the rat.
COG1410, a small, novel ApoE-mimetic peptide derived from the receptor binding region of apolipoprotein E (ApoE), has been classified as anti-inflammatory in nature and improves motor, sensorimotor, and cognitive dysfunction following cortical contusion injury (CCI). In order to further examine COG1410's preclinical efficacy on cognitive recovery, the present study evaluated COG1410 following moderate fluid percussion injury (FPI). Animals were prepared with a moderate, unilateral FPI over the hippocampus. Following FPI, animals received a regimen of five doses of COG1410 or vehicle at 2 and 4h (1.0mg/kg, i.v.) followed by additional doses administered 24, 48, and 72 h (1.0mg/kg, i.p.). Prior to injury, animals were trained for 4 days (4 trials/day) in the Morris water maze (MWM) and then tested for retrograde amnesia on post-FPI day 11 and then on a working memory task on day 18. Testing for motor dysfunction on the tapered balanced beam began on day 2 post-FPI. Administration of this regimen of COG1410 significantly improved retention of memory in the retrograde amnesia test compared to vehicle post-FPI. However, COG1410 did not significantly improve acquisition of working memory in the MWM. Motor dysfunction on the tapered beam post-FPI was improved in the COG1410-treated group compared to vehicle treatment. Cortical lesion analysis revealed that the COG1410-treated animals demonstrated significantly less tissue loss compared to vehicle-treated animals. The results of this study suggest that COG1410 significantly limited the behavioral dysfunction and tissue loss associated with FPI and demonstrated continued preclinical efficacy for TBI.
Kaufman
Nicholas A
NA
Restorative Neuroscience Laboratory, Center for Integrative Research in Cognitive and Neural Sciences, Department of Psychology, Southern Illinois University, Carbondale, IL, USA.
Beare
Jason E
JE
Tan
Arlene A
AA
Vitek
Michael P
MP
McKenna
Suzanne E
SE
Hoane
Michael R
MR
D000818:Animals; D001057:Apolipoproteins E / Q000008:administration & dosage* / Q000138:chemical synthesis; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology*; D003072:Cognition Disorders / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000293:injuries; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D008569:Memory Disorders / Q000150:complications / Q000188:drug therapy*; D051381:Rats; D020318:Rats, Long-Evans; D020127:Recovery of Function / Q000187:drug effects*
D001057:Apolipoproteins E; C524548:COG1410