Effects of dexmedetomidine combined with mild hypothermia on global cerebral ischemia-reperfusion injury in neonatal rats

Abstract

Objective To evaluate the effects of combination of dexmedetomidine and mild hypothermia on global cerebral ischemia-reperfusion(I/R)injury in neonatal rats. Methods Ninety-six neonatal Sprague-Dawley rats, aged 6-7 days, weighing 18-22 g, were randomly divided into 4 groups(n=24 each)using a random number table: I/R group, mild hypothermia group(group H), dexmedetomidine group(group D)and combination of dexmedetomidine and mild hypothermia group(group DH). Global cerebral ischemia was induced in rats anaesthetized with chloral hydrate by bilateral common carotid artery clamping(for 15 min)combined with hypotension followed by reperfusion.Dexmedetomidine 75 μg/kg was given intraperitoneally at 30 min before ischemia in D and DH groups, while the equal volume of normal saline was given in I/R and H groups.The temperature in the temporal muscle was maintained at 36.7-37.2℃ in I/R and D groups, and at 34.8-35.3℃ in H and DH groups.At 12, 24 and 72 h of reperfusion, 8 rats were randomly chosen in each group, and neurological deficit score(NDS)was determined.The animals were then sacrificed, and their brains were removed for determination of myeloperoxidase(MPO)activity(by spectrophotometry)and contents of tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in brain tissues(using ELISA). Results Compared with I/R group, the NDS, MPO activity and contents of TNF-α and IL-6 were significantly decreased in the other three groups.The NDS, MPO activity and contents of TNF-α and IL-6 were significantly lower in DH group than in H or D group. Conclusion Dexmedetomidine can optimize cerebral protection providedby mild hypothermia against global cerebral I/R injury through inhibiting inflammatory responses in brain tissues of neonatal rats. Key words: Dexmedetomidine; Hypothermia, induced; Infant, newborn; Reperfusion injury; Brain