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 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.
Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China; Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, PR China.
Shu-Zhen
SZ
Zhu
Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
Yong
Y
Gu
Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
Zhou
Z
Wu
Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
Ya-Fang
YF
Hu
Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China. Electronic address: pansuyue82@126.com.
Su-Yue
SY
Pan
D000818:Animals; D007036:Hypothermia, Induced / Q000009:adverse effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017694:Rewarming / Q000009:adverse effects*; D020521:Stroke / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D018746:Systemic Inflammatory Response Syndrome / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D016896:Treatment Outcome
Blood–brain barrier; Hypothermia; Inflammatory response; Ischemic stroke; Rapid rewarming