Insulin-like growth factor-1 improves somatosensory function and reduces the extent of cortical infarction and ongoing neuronal loss after hypoxia-ischemia in rats

Treatment with insulin-like growth factor-1 has been demonstrated to reduce the extent of cortical infarction 5 days after hypoxic-ischemic, brain inj ury. As neuronal death can be progressive and long lasting after initial in jury, the present study examined the long-term effects of insulin-like grow th factor-1 on late neuronal loss 20 days after hypoxic-ischemic injury, to gether with evaluating neurobehavioral outcome as assumed by somatosensory function. Unilateral brain injury was induced in adult rats by carotid artery ligatio n followed by 10 min of hypoxia (6% O-2). A single dose of insulin-like gro wth factor-1 (50 mug) was administered intracerebroventricularly via a ster eotaxically prefixed cannula 2 h after injury. A bilateral tactile stimulat ion test was used to examine the degree of somatosensory function at 3, 5, 10 and 20 days after the hypoxia in both insulin-like growth factor-1- (n = 12) and its vehicle- (n = 12) treated rats, along with sham-operated rats (n = 9). Cortical infarction and percentage of selective neuronal loss in t he cerebral cortex were examined 20 days after the hypoxic-ischemic injury in both treatment groups. Hypoxic-ischemic injury resulted in a significant delay in the time taken t o contact the patch over the period examined (left/right ratio 5.1 +/- 0.79 ), particularly at 3 days (7.0 +/- 2.8) after the hypoxia, compared to sham -operated rats (1.1 +/- 0.9, P < 0.05). The overall effect of insulin-like growth factor-1 in reducing the time taken to contact the patch was signifi cant (P = 0.03, 2.6 +/- 0.79) compared to the vehicle group. There was a tr end towards a reduction of cortical infarction after insulin-like growth fa ctor-1 treatment (P = 0.058), however insulin-like growth factor-1 signific antly reduced the percentage of selective neuronal loss (P = 0.027) 20 days following the hypoxia. From these data we suggest that insulin-like growth factor-1 improves somatosensory function by reducing both the extent of co rtical infarction and ongoing progressive neuronal death during brain recov ery from hypoxic-ischemic injury. (C) 2001 IBRO. Published by Elsevier Scie nce Ltd. All rights reserved.