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Intestinal ischemia/reperfusion enhances microglial activation and induces cerebral injury and memory dysfunction in rats.

Abstract：

OBJECTIVE:The mortality of critically ill patients associated with intestinal ischemia/reperfusion remains very high, which results from multiorgan dysfunction or failure due to intestinal injury induced by intestinal ischemia/reperfusion. This study was carried out to investigate whether intestinal ischemia/reperfusion can cause cerebral injury and concomitant memory dysfunction, and explore the potential mechanisms. DESIGN:Prospective, controlled, and randomized animal study. SETTING:University research laboratory. SUBJECTS:Male, adult Sprague-Dawley rats (weighing 250-300 g). INTERVENTIONS:Intestinal ischemia/reperfusion was established by clamping the superior mesenteric artery for 90 mins followed by different reperfusion durations (2, 6, 12, 24, or 48 hrs). The sham surgical preparation including isolation of the superior mesenteric artery without occlusion was performed as control. MEASUREMENTS AND MAIN RESULTS:In comparison with sham control, intestinal ischemia/reperfusion caused severe intestinal injury, accompanied by notable cerebral damage evidenced by increased wet-to-dry brain weight ratio reflecting brain edema and neuronal cell apoptosis manifested by increased apoptotic cell number and cleaved caspase-3 protein expressions. All these changes were concomitant with reduced survival rates as well as impaired memory function determined by Morris water maze test at 24 and 48 hrs after reperfusion. In addition, intestinal ischemia/reperfusion resulted in significant increases in the levels of tumor necrosis factor-α and interleukin-6 both in the serum and in cortices and hippocampal Cornu Ammonis area 1 regions, concomitant with the activation of microglia, a key cellular mediator involved in neuroinflammation and neurodegeneration, which was evidenced by increased protein expressions of ionized calcium binding adaptor molecule 1. Furthermore, the releases of reactive oxygen species evidenced by increased malondialdehyde levels and decreased superoxide dismutase activities in cortices and hippocampal Cornu Ammonis area 1 regions were found after reperfusion. CONCLUSIONS:These findings indicate that intestinal ischemia/reperfusion-induced intestinal injury can lead to cerebral damage and memory dysfunction partly via microglia activation which further facilitates oxidative injury, inflammatory response, and neuronal cell apoptosis.

journal_name

Crit Care Med

journal_title

Critical care medicine

authors

Zhou J,Huang WQ,Li C,Wu GY,Li YS,Wen SH,Lei WL,Liu KX

doi

10.1097/CCM.0b013e3182546855

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

2438-48

issue

eissn

0090-3493

issn

1530-0293

journal_volume

pub_type

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Intestinal ischemia/reperfusion enhances microglial activation and induces cerebral injury and memory dysfunction in rats.