Acute kidney injury leads to inflammation and functional changes in the brain.
Acute kidney injury leads to inflammation and functional changes in the brain.
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DOI：
10.1681/asn.2007080901
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发表时间：
2008-07
期刊：
影响因子：
--
通讯作者：
Rabb H
中科院分区：
文献类型：
--
作者：
Liu M;Liang Y;Chigurupati S;Lathia JD;Pletnikov M;Sun Z;Crow M;Ross CA;Mattson MP;Rabb H
Although neurological sequelae of acute kidney injury (AKI) are well established, the pathogenesis of acute uremic encephalopathy is poorly understood. We examined the short-term effect of severe ischemic AKI on mouse brain inflammatory and functional changes. C57BL/6 mice underwent a 60 min of bilateral renal ischemia or a sham operation and the brains were harvested and studied at 24 h after surgery. Compared to sham operated mice, the mice with AKI had significantly increased concentration of C reactive protein and chemokine G-CSF in the blood and increased the numbers of pyknotic neurons and microgliosis in the brain. AKI mice had increased levels of proinflammatory chemokine proteins KC and G-CSF in both cerebral cortex and hippocampus when compared to sham operated mice. There was increased glial fibrillary acidic protein (GFAP) expression in astrocytes in the cortex and corpus callosum after AKI. In contrast, no increased neuronal pyknosis or increased expression of GFAP was found in the brain from mice with ischemic acute liver injury and normal renal function. Mice with AKI also had increased brain Evans blue dye extravasation into the brain suggesting disruption of the blood-brain barrier.. To evaluate the functional effects of different severities of AKI, we studied locomotor activity using an open field test. Mice with either a 45 or 60 min renal ischemia or a bilateral nephrectomy had moderate to severe decline in locomotor activity 24 h after surgery when compared to sham operated mice. This is the first demonstration that severe ischemic AKI induces brain inflammation and ischemic time-dependent functional changes. Targeting these pathways could reduce morbidity and mortality in critically ill patients with severe AKI.
