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CNS Neurosci Ther. 2014 Jan;20(1):67-75. doi: 10.1111/cns.12160. Epub 2013 Aug 24.

Moderate hypothermia inhibits brain inflammation and attenuates stroke-induced immunodepression in rats.

Author information

1
Department of Neurosurgery, Stanford Stroke Center and Stanford Institute for Neuro-Innovation and Translational Neurosciences, Stanford University, Stanford, CA, USA; Department of Basic Medicine, Hangzhou Normal University, Hangzhou, China.

Abstract

AIMS:

Stroke causes both brain inflammation and immunodepression. Mild-to-moderate hypothermia is known to attenuate brain inflammation, but its role in stroke-induced immunodepression (SIID) of the peripheral immune system remains unknown. This study investigated the effects in rats of moderate intra-ischemic hypothermia on SIID and brain inflammation.

METHODS:

Stroke was induced in rats by permanent distal middle cerebral artery occlusion combined with transient bilateral common carotid artery occlusion, while body temperature was reduced to 30°C. Real-time PCR, flow cytometry, in vitro T-cell proliferation assays, in vivo delayed-type hypersensitivity (DTH) reaction and confocal microscopy were used to study SIID and brain inflammation.

RESULTS:

Brief intra-ischemic hypothermia helped maintain certain leukocytes in the peripheral blood and spleen and enhanced T-cell proliferation in vitro and delayed-type hypersensitivity in vivo, suggesting that hypothermia reduces SIID. In contrast, in the brain, brief intra-Ischemic hypothermia inhibited mRNA expression of anti-inflammatory cytokine IL-10 and proinflammatory mediators INF-γ, TNF-α, IL-2, IL-1β and MIP-2. Brief intra-Ischemic hypothermia also attenuated the infiltration of lymphocytes, neutrophils (MPO(+) cells) and macrophages (CD68(+) cells) into the ischemic brain, suggesting that hypothermia inhibited brain inflammation.

CONCLUSIONS:

Brief intra-ischemic hypothermia attenuated SIID and protected against acute brain inflammation.

KEYWORDS:

Focal cerebral ischemia; Hypothermia; Immunodepression; Inflammation; Leukocytes

PMID:
23981596
PMCID:
PMC3867545
DOI:
10.1111/cns.12160
[Indexed for MEDLINE]
Free PMC Article

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