Hypothermia followed by rapid rewarming exacerbates ischemia-induced brain injury and augments inflammatory response in rats

Hypothermia followed by slow rewarming is neuroprotective for ischemic stroke. However, slow rewarming causes patients' longer stay in intensive care unit and increases the risk of hypothermic complications. Hypothermia followed by rapid rewarming (HTRR) is more convenient; but it exacerbates i...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2016-05, Vol.474 (1), p.175-181
Main Authors: Zhu, Shu-Zhen, Gu, Yong, Wu, Zhou, Hu, Ya-Fang, Pan, Su-Yue
Format: Article
Language:English
Subjects:
Animals
Blood–brain barrier
Hypothermia
Hypothermia, Induced - adverse effects
Inflammatory response
Ischemic stroke
Male
Rapid rewarming
Rats
Rats, Sprague-Dawley
Rewarming - adverse effects
Stroke - diagnosis
Stroke - etiology
Stroke - physiopathology
Systemic Inflammatory Response Syndrome - diagnosis
Systemic Inflammatory Response Syndrome - etiology
Systemic Inflammatory Response Syndrome - physiopathology
Treatment Outcome
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Summary:Hypothermia followed by slow rewarming is neuroprotective for ischemic stroke. However, slow rewarming causes patients' longer stay in intensive care unit and increases the risk of hypothermic complications. Hypothermia followed by rapid rewarming (HTRR) is more convenient; but it exacerbates intracranial hypertension for patients with massive hemispheric infarcts. The present study aims to investigate in detail how HTRR exacerbates ischemic brain injury and what are underlying mechanisms. Rats subjected to transient focal ischemia by middle cerebral artery occlusion were treated with normothermia or hypothermia followed by rapid rewarming. Neurological outcome, neuronal injury, blood–brain barrier integrity and expressions of inflammatory cytokines were observed. Results showed that HTRR at a rate of 3 °C/20 min increased both neurological deficit score and Longa score, enhanced the loss of neurons and the plasma level of neuron-specific enolase. Rapid rewarmed rats also displayed increased Evans blue dye extravasation, matrix metalloproteinase 9 level and tight junction impairment. Meanwhile, interleukin-1β, -6, tumor necrosis factor α and cyclooxygenase-2 were markedly elevated in rapid rewarmed rats. Anti-inflammatory agent minocycline suppressed HTRR-induced elevation of inflammatory cytokines and improved neurological outcome. These results indicated that HTRR significantly impaired neurovascular unit and augmented proinflammatory response in stroke. [Display omitted] •Hypothermia followed by rapid rewarming (HTRR) increased Longa score and neurological deficit score.•HTRR augmented the neuronal loss and the elevation of plasma NSE level in stroke model.•HTRR increased the extravasation of Evans blue dye, enhanced MMP9 release and decreased tight junction proteins.•HTRR increased the levels of cytokines, while minocycline reduced inflammation and improved neurological outcome.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2016.04.095