Insulin-like growth factor (IGF-1) is induced in damaged brain tissue after
hypoxia-
ischemia, and exogenous administration of
IGF-1 shortly after injury has been shown to be neuroprotective. However, it is unknown whether treatment with
IGF-1 delayed by more than a few hours after injury may be protective.
Hypothermia after
brain injury has been reported to delay the development of ischemic neuronal death. The authors therefore hypothesize that a reduction in the environmental temperature during recovery from
hypoxia-
ischemia could prolong the window of opportunity for
IGF-1 treatment. Unilateral brain damage was induced in adult rats using a modified Levine model of right carotid artery
ligation followed by brief
hypoxia (6% O2 for 10 minutes). The rats were maintained in either a warm (31 degrees C) or cool (23 degrees C) environment for the first 2 hours after
hypoxia. All rats were subsequently transferred to the 23 degrees C environment until the end of the experiment. A single dose of
IGF-1 (50 microg) or its vehicle was given intracerebroventricularly at either 2 or 6 hours after
hypoxia. Histologic outcome in the lateral cortex was quantified 5 days after
hypoxia. Finally, cortical temperature was recorded from 1 hour before and 2 hours after
hypoxia in separate groups of rats exposed to the "warm" and "cool" protocols. In rats exposed to the warm recovery environment,
IGF-1 reduced cortical damage (P < 0.05) when given 2 hours but not 6 hours after insult. In contrast, with early recovery in the cool environment, a significant protective effect of
IGF-1 in the lateral cortex (P < 0.05) was found with administration 6 hours after insult. In conclusion, a reduction in cerebral temperature during the early recovery phase after severe
hypoxia-
ischemia did not significantly reduce the severity of injury after 5 days' recovery; however, it markedly shifted and extended the window of opportunity for
delayed treatment with
IGF-1.