TY - JOUR
T1 - COG1410, an apolipoprotein E-based peptide, improves cognitive performance and reduces cortical loss following moderate fluid percussion injury in the rat
AU - Kaufman, Nicholas A.
AU - Beare, Jason E.
AU - Tan, Arlene A.
AU - Vitek, Michael P.
AU - McKenna, Suzanne E.
AU - Hoane, Michael R.
N1 - Funding Information:
Funding provided by Cognosci Inc. grants R44NS048689 and R44AG020473 from the NIH. Special thanks to Andrea Quigley, Keith Gregory, and Sarah Heck for technical assistance. Cognosci, Inc. has filed for patent protection for COG1410.
PY - 2010/12
Y1 - 2010/12
N2 - 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 4. h (1.0. mg/kg, i.v.) followed by additional doses administered 24, 48, and 72. h (1.0. mg/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.
AB - 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 4. h (1.0. mg/kg, i.v.) followed by additional doses administered 24, 48, and 72. h (1.0. mg/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.
KW - Amnesia
KW - FPI
KW - Recovery of function
KW - Therapy
KW - Traumatic brain injury
KW - Treatment
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U2 - 10.1016/j.bbr.2010.06.017
DO - 10.1016/j.bbr.2010.06.017
M3 - Article
C2 - 20600347
AN - SCOPUS:77955275113
SN - 0166-4328
VL - 214
SP - 395
EP - 401
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 2
ER -