The novel apolipoprotein E-based peptide COG1410 improves sensorimotor performance and reduces injury magnitude following cortical contusion injury.
It has previously been shown that small peptide molecules derived from the apolipoprotein E (ApoE) receptor binding region are anti-inflammatory in nature and can improve outcome following head injury. The present study evaluated the preclinical efficacy of COG1410, a small molecule ApoE-mimetic peptide (1410 daltons), following cortical contusion injury (CCI). Animals were prepared with a unilateral CCI of the sensorimotor cortex (SMC) or sham procedure. Thirty mins post-CCI the animals received i.v. infusions of 0.8 mg/kg COG1410, 0.4 mg/kg COG1410, or vehicle. Starting on day 2, the animals were tested on a battery of behavioral measures to assess sensorimotor (vibrissae-forelimb placing and forelimb use-asymmetry), and motor (tapered balance beam) performance. Administration of the 0.8 mg/kg dose of COG1410 significantly improved recovery on the vibrissae-forelimb and limb asymmetry tests. However, no facilitation was observed on the tapered beam. The low dose (0.4 mg/kg) of COG1410 did not show any significant differences compared to vehicle. Lesion analysis revealed that the 0.8 mg/kg dose of COG1410 significantly reduced the size of the injury cavity compared to the 0.4 mg/kg dose and vehicle. The 0.8 mg/kg dose also reduced the number of glial fibrillary acid protein (GFAP+) reactive cells in the injured cortex. These results suggest that a single dose of COG1410 facilitates behavioral recovery and provides neuroprotection in a dose and task-dependent manner. Thus, the continued clinical development of ApoE based therapeutics is warranted and could represent a novel strategy for the treatment of traumatic brain injuries.
Hoane
Michael R
MR
Restorative Neuroscience Laboratory, Center for Integrative Research in Cognitive and Neural Sciences, Department of Psychology, Southern Illinois University, Carbondale, Illinois 62901, USA. mhoane@siu.edu
Pierce
Jeremy L
JL
Holland
Michael A
MA
Birky
Nicholas D
ND
Dang
Tan
T
Vitek
Michael P
MP
McKenna
Suzanne E
SE
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001057:Apolipoproteins E / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects / Q000378:metabolism; D005911:Gliosis / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D008297:Male; D009068:Movement / Q000187:drug effects / Q000502:physiology; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D001057:Apolipoproteins E; C524548:COG1410; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D010455:Peptides