Acute Kidney Injury Induces Neurological Impairment Through Early Blood-Brain Barrier Disruption and Endothelial...

Acute kidney injury (AKI) is associated with central neurologic complications, notably in critical care, the mechanisms of which are poorly understood. Blood-brain barrier (BBB) disruption is a central mechanism associated with cognitive impairment in chronic kidney disease. The objectives of this study were to characterize the influence of AKI on brain alteration and BBB permeability in a preclinical model.

We performed a mouse model of unilateral renal ischemia-reperfusion injury without or with AKI (obtained by removing the contralateral kidney before ischemia).

All animals were 7-week-old male C57Bl/6J mice, randomly assigned to groups: AKI, kidney ischemia-reperfusion alone, or control.

We assessed neurologic impairment using the modified neurologic severity score and motricity evaluations, quantified BBB disruption by cerebral extravasation of Evans blue and positron emission tomography (PET)/CT imaging with Gallium-68 diethylenetriaminepentaacetic acid (68Ga-DTPA), and performed immunohistochemistry and electron microscopy on brain sections.

In mice with AKI, we found neurologic impairment, decreased spontaneous motricity, and cerebral extravasation of Evans blue, which were not observed in mice with renal ischemia-reperfusion without nephrectomy. Cerebral 68Ga-DTPA PET/CT imaging with imaging confirmed the BBB disruption. In addition, we observed more extracellular vesicles in cerebral endothelial cells by electron microscopy in AKI mice compared with controls.

AKI-induced neurologic complications are associated with an early increase in BBB permeability and transcytosis of extracellular vesicles in cerebral endothelium.