Changes in Insulin-like Growth Factor 1 Receptor Density after Transient Cerebral Ischemia in the Rat. Lack of Protection against Ischemic Brain Damage following Injection of Insulin-Like Growth Factor 1

Binding of ¹²⁵I-insulin-like growth factor-1 (¹²⁵I-IGF-1) to rat brain slices was studied after 15 min of two-vessel occlusion ischemia and 1 h to 4 days of recirculation. Ligand binding in the hippocampus increased at 6 h post ischemia in the CA₁ and CA₃ regions and the dentate gyrus, suggesting that the IGF-1 receptors were up-regulated, while no change was seen in neocortex and striatum. Intracerebroventricular injections of IGF-1 (2 μg) prior to and after transient cerebral ischemia did not reduce neuronal damage. The increased up-regulation on IGF-1 receptors and the absence of neuroprotection by IGF-1 suggest that the intracellular signal transduction chain activated by the IGF-1 receptor may be interrupted.