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

Neuroscience. 2001;105(2):299-306. doi: 10.1016/s0306-4522(01)00145-2.

Abstract

Treatment with insulin-like growth factor-1 has been demonstrated to reduce the extent of cortical infarction 5 days after hypoxic-ischemic brain injury. As neuronal death can be progressive and long lasting after initial injury, the present study examined the long-term effects of insulin-like growth factor-1 on late neuronal loss 20 days after hypoxic-ischemic injury, together with evaluating neurobehavioral outcome as assumed by somatosensory function. Unilateral brain injury was induced in adult rats by carotid artery ligation followed by 10 min of hypoxia (6% O2). A single dose of insulin-like growth factor-1 (50 microg) was administered intracerebroventricularly via a stereotaxically pre-fixed cannula 2 h after injury. A bilateral tactile stimulation 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 the 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 to 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 significant (P=0.03, 2.6+/-0.79) compared to the vehicle group. There was a trend towards a reduction of cortical infarction after insulin-like growth factor-1 treatment (P=0.058), however insulin-like growth factor-1 significantly 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 cortical infarction and ongoing progressive neuronal death during brain recovery from hypoxic-ischemic injury.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Cell Count
  • Cerebral Infarction / drug therapy*
  • Cerebral Infarction / pathology
  • Cerebral Infarction / physiopathology
  • Hypoxia-Ischemia, Brain / drug therapy*
  • Hypoxia-Ischemia, Brain / pathology
  • Hypoxia-Ischemia, Brain / physiopathology
  • Insulin-Like Growth Factor I / pharmacology*
  • Male
  • Necrosis
  • Nerve Degeneration / drug therapy*
  • Nerve Degeneration / etiology
  • Nerve Degeneration / pathology
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Wistar
  • Recovery of Function / drug effects
  • Recovery of Function / physiology
  • Somatosensory Cortex / drug effects*
  • Somatosensory Cortex / pathology
  • Somatosensory Cortex / physiopathology
  • Somatosensory Disorders / drug therapy*
  • Somatosensory Disorders / etiology
  • Somatosensory Disorders / pathology
  • Touch / drug effects
  • Touch / physiology
  • Treatment Outcome

Substances

  • Neuroprotective Agents
  • Insulin-Like Growth Factor I