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.
Wang
Lai Shuan
LS
Department of Pediatrics, Children's Hospital of Fudan University, 183 Feng-lin Road, Shanghai 200032, China.
Zhou
Jin
J
Shao
Xiao Mei
XM
Tang
Xi Can
XC
D000470:Alkaloids; D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D002339:Carotid Arteries; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D014867:Water
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D012717:Sesquiterpenes; C050426:huperzine A; D014867:Water