Neuroprotective pentapeptide CN-105 improves functional and histological outcomes in a murine model of intracerebral hemorrhage.
Presently, no pharmacological treatments have been demonstrated to improve long-term functional outcomes following intracerebral hemorrhage (ICH). Clinical evidence associates apolipoprotein E (apoE) genotype with ICH incidence and outcome. While apoE modifies neuroinflammatory responses through its adaptive role in glial downregulation, intact apoE holoprotein is too large to cross the blood-brain barrier (BBB). Therefore, we developed a 5-amino acid peptide - CN-105 - that mimics the polar face of the apoE helical domain involved in receptor interactions. In the current study, we investigated the therapeutic potential of CN-105 in a mouse model of ICH. Three doses of CN-105 (0.05 mg/kg) was administered by tail vein injection within 24 hours after ICH induction. Functional assessment showed durable improvement in vestibulomotor performance after CN-105 treatment, as quantified by increased Rotarod latencies on Days 1-5 post-ICH, and long-term improvement in neurocognitive performance, as quantified by reduced Morris water maze latencies on Days 29-32 post-ICH. Further, brain water content was significantly reduced, neuroinflammation was decreased and hippocampal CA3 neuronal survival was increased, although hemorrhage volume was not affected by CN-105. We concluded, therefore, that pentapeptide CN-105 improved short- and long-term neurobehavioral outcomes in a murine model of ICH, suggesting therapeutic potential for patients with acute ICH.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
EISSN
Publication Date
Volume
Start / End Page
Location
Related Subject Headings
- Rotarod Performance Test
- Oligopeptides
- Neuroprotective Agents
- Neurons
- Mice, Inbred C57BL
- Male
- Disease Models, Animal
- Cerebral Hemorrhage
- Cell Survival
- CA3 Region, Hippocampal
Citation
Published In
DOI
EISSN
Publication Date
Volume
Start / End Page
Location
Related Subject Headings
- Rotarod Performance Test
- Oligopeptides
- Neuroprotective Agents
- Neurons
- Mice, Inbred C57BL
- Male
- Disease Models, Animal
- Cerebral Hemorrhage
- Cell Survival
- CA3 Region, Hippocampal