Published Online
on September 11, 2003

A more recent version of this article appeared on October 1, 2003

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Submitted on May 8, 2003
Accepted on June 20, 2003

Mild Hypothermia Inhibits Inflammation After Experimental Stroke and Brain Inflammation

Holly Deng BS; Hyung Soo Han MD, PhD; Danye Cheng MS; Guo Hua Sun MD, PhD; and Midori A. Yenari MD^*

From the Departments of Neurosurgery (H.D., H.S.H., D.C., G.H.S., M.A.Y.) and Neurology (H.D., H.S.H., M.A.Y.), Stanford University, Stanford, Calif.

^* To whom correspondence should be addressed. E-mail: yenari{at}alum.mit.edu.

Background and Purpose--We previously showed that mild hypothermia protects against experimental stroke, even when cooling was delayed by 2 hours. Protection may be due in part to inhibiting inflammation. To clarify, we examined leukocyte infiltration, microglial activation, and adhesion molecule expression in models of stroke and pure brain inflammation.

Methods--Rats underwent 2-hour middle cerebral artery occlusion (MCAO; n=36) or intravenous injection with 5 mg/kg lipopolysaccharide (LPS; n=22). Temperature was lowered to 33°C for 2 hours or kept at 37°C. In MCAO, cooling was applied intraischemically or on reperfusion (delayed). In the LPS model, cooling began after injection. One and 3 days later, brains were assessed for neutrophils, monocytes/microglia, major histocompatibility complex class II antigen, and intercellular adhesion molecule-1 (ICAM-1).

Results--One day after MCAO, both intraischemic and delayed hypothermia decreased ICAM-1 (51% and 60%, respectively, versus normothermia; P<0.001), monocytes (63% and 57%; P<0.01), and microglia (55% and 53%; P<0.001). Similar decreases were seen at 3 days for ICAM-1 (91% and 93%; P<0.001), monocytes (62% and 54%; P<0.01), and microglia (55% and 53%; P<0.001). In the LPS model, ED-1-positive cells were not observed in the brain, but hypothermia decreased ICAM-1 (26%; P<0.05), OX6 (56%; P<0.01), and microglia (47%; P<0.01) at 1 day.

Conclusions--Mild hypothermia decreases inflammatory responses in both brain inflammation and stroke, implicating a direct anti-inflammatory effect of cooling. This suggests that hypothermia can attenuate factors contributing to delayed ischemic injury.

Key words: hypothermia • inflammation • ischemia • rats

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