Benzamide protects delayed neuronal death and behavioural impairment in a mouse model of global cerebral ischemia.
The present study is aimed at evaluating the functional and neuroprotective effect of benzamide, a poly-(ADP-ribose) polymerase (PARP) inhibitor on delayed neuronal death (DND) in hippocampus CA1 region and memory impairment following global cerebral ischemia (GCI) in a mouse model. GCI was induced by bilateral common carotid artery occlusion (BCAo) for 20 min followed by reperfusion for 9 days. Postischemic continuous treatment with benzamide (160 mg/kg b w i.p. for 9 days) significantly reversed the GCI-induced anterograde memory impairment in passive avoidance step through and elevated plus maze tasks. The observed memory impairment in vehicle treated ischemia group was found to be well correlated with DND and downregulation of cholinergic muscarinic receptor-1 expression, which was possibly mediated by inflammation and apoptosis, as revealed from inducible nitric oxide synthase (iNOS) expression and number of TUNEL positive neurons in hippocampus CA1 region. It is clear from the present experiment that benzamide treatment significantly decreases the iNOS expression and number of apoptotic neurons and thereby improves the neuronal survival and memory during GCI. Our present findings provide compelling evidence that multiple doses of benzamide treatment is a promising therapeutic approach for cerebrovascular and neurodegenerative diseases, which deserves further clinical evaluation.
Kumaran
D
D
Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110007, India.
Udayabanu
M
M
Nair
R Unnikrishnan
RU
R
Aneja
A
Katyal
Anju
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001157:Arterial Occlusive Diseases / Q000473:pathology / Q000503:physiopathology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002340:Carotid Artery Diseases / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D015200:Fluoroimmunoassay; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008845:Microinjections; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001549:Benzamides; C086088:CHRM1 protein, human; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; C037689:benzamide; D019001:Nitric Oxide Synthase