Renal ischemia/reperfusion induced learning and memory deficit in the rat: Insights into underlying molecular and cellular mechanisms.

Distance organ dysfunction is the major cause of death in the patients with acute kidney injury (AKI). However, the neurobiological basis of AKI-induced brain disorders and their mediators are poorly understood. This study was aimed to find out the links between AKI and brain injury and also the underlying cellular and electrophysiological mechanisms of memory deficit following induction of AKI via different experimental models of renal ischemia with or without uremia and uremia without renal ischemia. Fifty four male Sprague-Dawley rats were divided into 4 groups that underwent 1-h bilateral or 2-h unilateral renal ischemia followed by 1-day reperfusion (BIR and UIR, respectively), and 1-day following bilateral nephrectomy (BNX) or sham-operation. There were 2 subgroups in each group, which blood-brain barrier (BBB) integrity was evaluated in one subgroup. The other subgroup was used for recordings electrophysiological activities of the hippocampus; and after blood sampling and sacrificing animal, the cerebral hemispheres were removed and preserved for performing stereological study and Western-blotting of caspase-3 in the left and right hippocampus, respectively. Plasma urea and creatinine and CA1 neuronal loss were largely increased by BNX and BIR, but slightly by UIR. Apoptosis was stimulated in the hippocampus intensively by BIR but moderately by UIR and BNX. However, BIR and UIR were associated with profoundly disturbed BBB, increased CA1 neuronal excitability, impaired LTP induction and memory deficit. Therefore, AKI most likely through inflammatory mediators leads to hippocampal apoptosis and electrophysiological impairments, BBB disruption and memory loss, whereas uremia may contribute to necrotic neuronal death.