5′-Adenosine Monophosphate-Induced Hypothermia Attenuates Brain IschemiaReperfusion Injury in a Rat Model by Inhibiting the Inflammatory Response

Abstract EN

Hypothermia treatment is a promising therapeutic strategy for brain injury.

We previously demonstrated that 5′-adenosine monophosphate (5′-AMP), a ribonucleic acid nucleotide, produces reversible deep hypothermia in rats when the ambient temperature is appropriately controlled.

Thus, we hypothesized that 5′-AMP-induced hypothermia (AIH) may attenuate brain ischemia/reperfusion injury.

Transient cerebral ischemia was induced by using the middle cerebral artery occlusion (MCAO) model in rats.

Rats that underwent AIH treatment exhibited a significant reduction in neutrophil elastase infiltration into neuronal cells and matrix metalloproteinase 9 (MMP-9), interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and Toll-like receptor (TLR) protein expression in the infarcted area compared to euthermic controls.

AIH treatment also decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL-) positive neuronal cells.

The overall infarct volume was significantly smaller in AIH-treated rats, and neurological function was improved.

By contrast, rats with ischemic brain injury that were administered 5′-AMP without inducing hypothermia had ischemia/reperfusion injuries similar to those in euthermic controls.

Thus, the neuroprotective effects of AIH were primarily related to hypothermia.