Neuroprotective effects of insulin-like growth factor-I (IGF-I) following a penetrating brain injury in rats.

The elucidation of the molecular mechanisms involved in the response of brain tissue to trauma and the recognition of substances with neuroprotective properties is a prerequisite for the development of rational therapeutic approaches. In this study, we used a model of, unilateral, penetrating stab-like brain injury and examined the possible beneficial effects of post-injury administration of insulin-like growth factor-I (IGF-I) both at the cellular level, 4 and 12 h post-injury, and on the physical condition of the animals up to 1 week following the trauma. The consequences of injury were assessed by immunohistochemically observing the expression of heat-shock protein 70 (Hsp70), which is thought to be a marker of cell stress and injury, and by staining the tissue with the TUNEL reaction, in order to detect apoptotic cell death. Injury resulted in an increase in the number of Hsp70 and TUNEL positive cells in the peritraumatic area. The physical condition of the rats was followed by measuring body weight changes, food and water intake and by estimating their "motor activity". IGF-I administration resulted in a significant decrease in the number of Hsp70 and TUNEL positive cells in the peritraumatic area. Additionally, it improved the total "motor activity" of injured rats, increased food intake and attenuated the post-injury body weight loss. IGF-I thus emerges as a factor acting both at the cellular level as a neuroprotectant and at the systemic level as an anabolic agent.