Neuroprotective and antiamnesic effect of donepezil, a nicotinic acetylcholine-receptor activator, on rats with concussive mild traumatic brain injury.
In this study we evaluated the effect of donepezil on the neurodegeneration and behavioral impairments induced by mild traumatic brain injury (MTBI). Donepezil is an acetylcholinesterase inhibitor that is used to treat Alzheimer's disease. Donepezil was given orally to rats subjected to MTBI. Treatment with a single oral dose of donepezil (12mg/kg) immediately after injury significantly attenuated MTBI-induced neuronal death and cognitive impairment as measured by preservation of neurons in the CA1 region of the hippocampus and a water maze test respectively. However, these neuroprotective effects were prevented by concomitant injection of mecamylamine, a nicotinic acetylcholine-receptor (nAChR) antagonist, indicating that protection is mediated by nAChR activation.
Fujiki
Minoru
M
Department of Neurosurgery, School of Medicine, Oita University, Oita, Japan. fujiki@med.oita-u.ac.jp
Kubo
Takeshi
T
Kamida
Tohru
T
Sugita
Kenji
K
Hikawa
Takamitsu
T
Abe
Tatsuya
T
Ishii
Keisuke
K
Kobayashi
Hidenori
H
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001924:Brain Concussion / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D000077265:Donepezil; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D009410:Nerve Degeneration / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018722:Nicotinic Agonists / Q000494:pharmacology / Q000627:therapeutic use; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D007189:Indans; D018696:Neuroprotective Agents; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D018697:Nootropic Agents; D010880:Piperidines; D011978:Receptors, Nicotinic; D000077265:Donepezil