Combination therapy with insulin-like growth factor-1 and hypothermia synergistically improves outcome after transient global brain ischemia in the rat.

Objectives: Hypothermia has a well-established neuroprotective effect and offers a foundation for combination therapy for brain ischemia. The authors evaluated the effect of combination therapy with insulin-like growth factor-1 (IGF-1) and hypothermia on brain structure and function in the setting of global brain ischemia and reperfusion in rats.

Methods: Male Sprague-Dawley rats were randomly assigned to groups by a registrar.

Acute administration of ethanol reduces apoptosis following ischemic stroke in rats.

In recent studies, acute ethanol administration appears to play a neuroprotective role during ischemic stroke. We sought to confirm these findings by identifying if ethanol-derived neuroprotection is associated with a reduction in apoptosis. Ethanol at 0.

The "Refrige-a-RAT-or": an accurate, inexpensive, and clinically relevant small animal model of therapeutic hypothermia.

Background: Physical and molecular mechanisms for the neuroprotective effect of therapeutic hypothermia are not completely understood, and new therapeutic applications incorporating hypothermia remain to be developed and tested. Clinically relevant animal models of therapeutic hypothermia are not well established or consistent.

Objectives: The objective was to develop and test an inexpensive small animal therapeutic hypothermia system that models those in widespread clinical use and verify that such a system confers neuroprotection in a rat model of global brain ischemia.

Neuroprotective effect of acute ethanol administration in a rat with transient cerebral ischemia.

Background And Purpose: Ethanol consumption is inversely associated with the risk of ischemic stroke, suggesting a neuroprotective effect. In a rat model of transient cerebral ischemia, we identified ethanol as a possible treatment for acute ischemic stroke.

Methods: Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2 hours.

Insulin activates the PI3K-Akt survival pathway in vulnerable neurons following global brain ischemia.

Unlabelled: Insulin is neuroprotective following transient global brain ischemia; however, the mechanisms by which insulin exerts its salutary effects remain unclear.

Objective: We assessed insulin's effect on the PI3K-Akt survival system and consequent modulation of the pro-apoptotic proteins Bim, Bad and FoxO3a.

Methods: We utilized rats subjected to 10 minutes of global brain ischemia, with or without insulin administered at the onset of reperfusion.

Insulin blocks cytochrome c release in the reperfused brain through PI3-K signaling and by promoting Bax/Bcl-XL binding.

The critical event of the intrinsic pathway of apoptosis following transient global brain ischemia is the release of cytochrome c from the mitochondria. In vitro studies have shown that insulin can signal specifically via phosphatidylinositol-3-OH-kinase (PI3-K) and Akt to prevent cytochrome c release. Therefore, insulin may exert its neuroprotective effects during brain reperfusion by blocking cytochrome c release.

Characterization of the eIF2-associated protein p67 during brain ischemia and reperfusion.

Objectives: Within the first few minutes of reperfusion after global brain ischemia, there is a severe depression of protein translation owing to phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 (eIF2). There is a 67 kDa peptide (p67) that, in its glycosylated form, binds to eIF2 and protects eIF2alpha from phosphorylation. Moreover, cells with high p67 content exhibit enhanced resistance to eIF2alpha phosphorylation.