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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / immunology
  • Brain / metabolism
  • Brain / pathology
  • Cytokines / metabolism
  • Encephalitis / etiology
  • Encephalitis / pathology
  • Encephalitis / physiopathology
  • Encephalitis / therapy*
  • Gene Expression Regulation
  • Hypothermia, Induced*
  • Immune Tolerance*
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / immunology
  • Infarction, Middle Cerebral Artery / physiopathology
  • Infarction, Middle Cerebral Artery / therapy
  • Leukocytes / physiology
  • Leukocytes, Mononuclear / immunology
  • Male
  • Neuroimmunomodulation*
  • Rats
  • Rats, Sprague-Dawley
  • Spleen / immunology
  • Stroke / complications
  • Stroke / immunology*
  • Stroke / physiopathology
  • Stroke / therapy*
  • T-Lymphocytes / immunology


  • Cytokines