Neuroprotective effect of nitroglycerin in a rodent model of ischemic stroke: evaluation of Bcl-2 expression.
Transient focal ischemia caused by middle cerebral artery occlusion (MCAo) produces apoptotic cell death in the penumbra area. Bcl-2 is a protooncogene that plays a major antiapoptotic role, at the cellular level, by counteracting the activation of apoptosis effectors, that is, caspases. It has been suggested that nitroglycerin (NTG), a nitric oxide donor, reduces ischemia/reperfusion-induced brain damage via the inhibition of caspase activity and NMDA receptor. In this chapter, we evaluated the protective effects of NTG against cerebral damage caused by transient (2h) MCAo (tMCAo) focusing our interest on the potential effects on Bcl-2 expression. Male Wistar rats were administered intraperitoneally (i.p.) with NTG (10mg/kg) or vehicle (PEG, 1ml/kg) 20min before the induction of MCAo by intraluminal silicon-coated filament (0.37-mm diameter). Cerebral infarct volume was measured 22h after reperfusion, while cortical Bcl-2 expression was evaluated at the end of 2-h MCAo (without reperfusion) and at 5h of reperfusion. The results show significant reduction of the infarct volume in rats preinjected with NTG, as compared to the vehicle group. After 2h of occlusion, no significant difference was seen in Bcl-2 expression in the ipsilateral and contralateral cortex of either experimental groups (NTG and vehicle). However, 5h after reperfusion, a significant increase of Bcl-2 expression was detected in the damaged cortex of control rats, probably reflecting a compensatory response aiming at counteracting the cell death process; this increase was absent in the NTG-treated rats. These data, while confirming the neuroprotective effect of NTG in an in vivo ischemia/reperfusion model, seem to suggest that the drug may act by downsizing the complex chain of events underlying apoptosis activation and consequent activation of antiapoptotic responses.
IRCCS C. Mondino Institute of Neurology Foundation, 27100 Pavia, Italy.
Rosaria
R
Greco
Diana
D
Amantea
Fabio
F
Blandini
Giuseppe
G
Nappi
Giacinto
G
Bagetta
M Tiziana
MT
Corasaniti
Cristina
C
Tassorelli
D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000150:complications*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D007839:Functional Laterality / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents; D005996:Nitroglycerin / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D014665:Vasodilator Agents / Q000494:pharmacology*
D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D014665:Vasodilator Agents; D005996:Nitroglycerin