Protective effects of acetyl-L-carnitine on neurodegenarative changes in chronic cerebral ischemia models and learning-memory impairment in aged rats.
This study investigated the effects of acetyl-L-carnitine (ALC) in secondarily-induced cerebral chronic ischemia models using rats with permanent ligation of bilateral common carotid arteries (BCCL) and spontaneously hypertensive rats (SHR). Additionally, we used normal aged rats as a primary dementia model. Chronic ALC administration at 100 mg/kg (p.o.) for 4 weeks significantly attenuated neurodegenerative changes. In groups receiving 50 mg/kg or 100 mg/kg, ALC inhibited the active astrocyte increase in cerebral tissues of both BCCL and SHR models. In BCCL rats, ALC administration (50 mg/kg or 100 mg/kg, p.o.) resulted in significant promotion of glutathione levels in brain tissues. We also confirmed behavioral improvement after ALC treatment (100 mg/kg for 8 weeks, p.o.) on learning-memory function using aged rats (18 months old) in a passive avoidance task and preservation of CA1 pyramidal neurons was coincided on histopathological observation. In conclusion, chronic ALC administration may ameliorate cerebral ischemia progress after a cerebrovascular disorder as well as spontaneous ageing-related cerebral dysfunction via hippocampal protection.
Preclinical Research Laboratories, Dong-A Pharmaceutical Company, Yongin 446-905, Korea. goomoonj@donga.co.kr
Moon-Jung
MJ
Goo
Seul Min
SM
Choi
Soon-Hoe
SH
Kim
Byoung Ok
BO
Ahn
D000108:Acetylcarnitine / Q000494:pharmacology / Q000627:therapeutic use*; D000375:Aging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008569:Memory Disorders / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR
D018696:Neuroprotective Agents; D000108:Acetylcarnitine