• DOI:10.1016/S0306-4522(01)00300-1
• Corpus ID: 54308982

The selective 5-HT1A receptor agonist repinotan HCl attenuates histopathology and spatial learning deficits following traumatic brain injury in rats

@article{Kline2001TheS5,
  title={The selective 5-HT1A receptor agonist repinotan HCl attenuates histopathology and spatial learning deficits following traumatic brain injury in rats},
  author={Anthony E. Kline and J. H. Yu and Ervin Horv{\'a}th and Donald W. Marion and C E Dixon},
  journal={Neuroscience},
  year={2001},
  volume={106},
  pages={547-555}
}

• A. Kline, J. Yu, +2 authors C. Dixon
• Published 27 September 2001
• Medicine
• Neuroscience

The selective 5-HT1A receptor agonist Repinotan HCl (BAY x3702) has been reported to attenuate cortical damage and improve functional performance in experimental models of cerebral ischemia and acute subdural hematoma. Using a clinically relevant contusion model of traumatic brain injury, we tested the hypothesis that a 4-h continuous infusion of Repinotan HCl (10 μg/kg/h i.v.) commencing 5 min post-injury would ameliorate functional outcome and attenuate histopathology. Forty isoflurane-anesthetized male adult rats were randomly assigned to receive either a controlled cortical impact (2.7 mm tissue deformation, 4 m/s) or sham injury (Injury/Vehicle=10, Injury/MK-801=10, Injury/Repinotan HCl=10, Sham/Vehicle=10), then tested for vestibulomotor function on post-operative days 1–5 and for spatial learning on days 14–18. Neither Repinotan HCl nor the non-competitive N-methyl-D-aspartate receptor antagonist MK-801, which served as a positive control, improved vestibulomotor function on beam balance and beam walk tasks relative to the Injury/Vehicle group, but both did significantly attenuate spatial learning and memory deficits on a water maze task. Repinotan HCl also reduced hippocampal CA1 and CA3 neuronal loss, as well as cortical tissue damage, compared to the Injury/Vehicle group at 4 weeks post-trauma. No significant difference in histological outcome was revealed between the Repinotan HCl- and MK-801-treated groups.

These findings extend the therapeutic efficacy of Repinotan HCl to a contusion model of experimental brain injury and demonstrate for the first time that 5-HT1A receptor agonists confer neuroprotection and attenuate spatial learning deficits following controlled cortical impact injury. This treatment strategy may be beneficial in a clinical context where memory impairments are common following human traumatic brain injury.