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The window of opportunity for neuronal rescue with insulin-like growth factor-1 after hypoxia-ischemia in rats is critically modulated by cerebral temperature during recovery.

  • Guan, J
  • Gunn, A J
  • Sirimanne, E S
  • Tuffin, J
  • Gunning, M I
  • Clark, R
  • Gluckman, P D
Published Article
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Publication Date
Mar 01, 2000
PMID: 10724116


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.

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