title: Acute kidney injury leads to inflammation and functional changes in the brain.
abstract: Although neurologic sequelae of acute kidney injury (AKI) are well described, the pathogenesis of acute uremic encephalopathy is poorly understood. This study examined the short-term effect of ischemic AKI on inflammatory and functional changes of the brain in mice by inducing bilateral renal ischemia for 60 min and studying the brains 24 h later. Compared with sham mice, mice with AKI had increased neuronal pyknosis and microgliosis in the brain. AKI also led to increased levels of the proinflammatory chemokines keratinocyte-derived chemoattractant and G-CSF in the cerebral cortex and hippocampus and increased expression of glial fibrillary acidic protein in astrocytes in the cortex and corpus callosum. In addition, extravasation of Evans blue dye into the brain suggested that the blood-brain barrier was disrupted in mice with AKI. Because liver failure also leads to encephalopathy, ischemic liver injury was induced in mice with normal renal function; neuronal pyknosis and glial fibrillary acidic protein expression were not increased, suggesting differential effects on the brain depending on the organ injured. For evaluation of the effects of AKI on brain function, locomotor activity was studied using an open field test. Mice subjected to renal ischemia or bilateral nephrectomy had moderate to severe declines in locomotor activity compared with sham-operated mice. These data demonstrate that severe ischemic AKI induces inflammation and functional changes in the brain. Targeting these pathways could reduce morbidity and mortality in critically ill patients with severe AKI.
authors.affiliation: Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA. manchang@jhmi.edu
authors.forename: Manchang
authors.initials: M
authors.lastname: Liu
authors.forename: Yideng
authors.initials: Y
authors.lastname: Liang
authors.forename: Srinivasulu
authors.initials: S
authors.lastname: Chigurupati
authors.forename: Justin D
authors.initials: JD
authors.lastname: Lathia
authors.forename: Mikhail
authors.initials: M
authors.lastname: Pletnikov
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Sun
authors.forename: Michael
authors.initials: M
authors.lastname: Crow
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ross
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.forename: Hamid
authors.initials: H
authors.lastname: Rabb
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000378:metabolism; D002199:Capillary Permeability / Q000502:physiology*; D004660:Encephalitis / Q000209:etiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D020287:In Situ Nick-End Labeling; D007511:Ischemia / Q000503:physiopathology; D017114:Liver Failure, Acute / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D014867:Water / Q000378:metabolism*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D011506:Proteins; D014867:Water; D016179:Granulocyte Colony-Stimulating Factor; D002097:C-Reactive Protein