Huperzine A attenuates cognitive deficits and brain injury in neonatal rats after hypoxia-ischemia.

The protective effects of huperzine A, a novel acetylcholinesterase inhibitor, on hypoxic-ischemic (HI) brain injury were investigated in neonatal rats. A unilateral HI brain injury was produced by the ligation of left common carotid artery followed by 1 h hypoxia with 7.7% oxygen in 7-day-old rat pups. After 5 weeks, HI brain injury in rat pups resulted in working memory impairments shown by increased escape latency in a water maze and reduced time spent in the target quadrant. The combination of common carotid artery ligation and exposure to a hypoxic environment caused the damage in the striatum, cortex, and hippocampus in the ipsilateral hemisphere, and the neuronal loss in the CA1 region. Huperzine A was administrated daily at the dose of 0.05 or 0.1 mg/kg i.p. for 5 weeks after HI injury. The significant protection against HI injury on behavior and neuropathology was produced by huperzine A at the dose of 0.1 mg/kg. These findings suggest that huperzine A might be beneficial in the treatment of hypoxic-ischemic encephalopathy in neonates.