The novel apolipoprotein E-based peptide COG1410 improves sensorimotor performance and reduces injury magnitude following cortical contusion injury
| Autor: | Nicholas D. Birky, Jeremy L. Pierce, Michael P. Vitek, Suzanne E. McKenna, Michael R. Hoane, Tan Dang, Michael A. Holland |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Apolipoprotein E
Male medicine.medical_specialty Movement Anti-Inflammatory Agents Peptide Neuroprotection Rats Sprague-Dawley Apolipoproteins E Internal medicine Glial Fibrillary Acidic Protein medicine Animals Gliosis Balance (ability) chemistry.chemical_classification Movement Disorders Dose-Response Relationship Drug business.industry Head injury Recovery of Function medicine.disease Cortex (botany) Rats Dose–response relationship Disease Models Animal Endocrinology medicine.anatomical_structure Neuroprotective Agents Treatment Outcome chemistry Anesthesia Astrocytes Brain Injuries Nerve Degeneration Neurology (clinical) Forelimb business Peptides |
| Zdroj: | Journal of neurotrauma. 24(7) |
| ISSN: | 0897-7151 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|