Insulin like growth factor-1 (IGF-1) decreases ischemia-reperfusion induced apoptosis and necrosis in diabetic rats.
Previous evidence supports the view that insulin, as well as insulin like growth factor-1 (IGF-1) provides neurotropic support for neurons in the central nervous system (CNS) and peripheral nervous system (PNS). In the present study we evaluated the effects of the intravenous infusion of IGF-1 on both necrosis and apoptosis in the CNS of streptozotocin induced diabetic animals before and/or following middle cerebral artery occlusion (MCAO) with reperfusion. The lesion volume was used as an index of necrosis and the sensorimotor cortex (layers 5 and 6) as well as the CA1 and CA3 regions of the hippocampus were analyzed for apoptosis using TUNEL staining and Caspase-3 immunoreactivity. A large lesion volume was produced in diabetic animals after 2-h MCAO and 24-h reperfusion. Diabetic animals also had an elevated basal level of apoptotic cells that are bilaterally distributed. Apoptosis was further increased over basal after 2-h MCAO and 24-h reperfusion. The acute administration of IGF-1 30-min before or 2 h after MCAO followed by 24-h reperfusion decreased the lesion volume as well as the number of apoptotic cells in the cortical penumbra. Apoptosis as assessed by TUNEL and caspase-3 immunoreactivity was decreased in select sensorimotor cortex and hippocampal areas. We conclude that treatment with IGF-1 before or after ischemic insult significantly decreases both lesion volume and apoptosis in selected areas of the cortex and hippocampus.
Rizk
Natalie N
NN
Department of Physiology, Wayne State University School of Medicine, 5374 Scott Hall, 540 E. Canfield, Detroit, MI 48201-1928, USA.
Myatt-Jones
Javar
J
Rafols
José
J
Dunbar
Joseph C
JC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009336:Necrosis / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
D007334:Insulin-Like Growth Factor I; D053148:Caspase 3
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