Abstract:  Objective To evaluate the effect of hepatic ischemia reperfusion on hippocampus and long-term cognitive function in young mice, and investigate the mechanisms related to N-methyl-D-aspartic acid receptor subunit 2A (NR2A) phosphorylation. Methods Fifty-four healthy C57 mice, 2-week old, with body mass 6-9 g, were randomly divided into three groups (n=18 / group): sham-operated group (S), hepatic ischemia reperfusion group (I) and NR2A inhibitor NVP- AAM077 treatment group (N). The mice in group N were given the intraperitoneal injection of NVP-AAM077 at the dose of 10 mg/kg for 3 days after the surgery. The mice in group S and group I were given equal amount of normal saline in the same way. Ten mice from each group were sacrificed 3 d after the surgery. Serum concentrations of S100β and neuron-specific enolase of enzyme (NSE) were detected by ELISA. Histopathological changes of hippocampus were determined by HE staining. Western blot assay was used to detect the expression levels of cleaved caspase-3 and NR2A, p-NR2A Y1325. Long-term cognitive function was evaluated by Morris water maze 30 d after surgery. Results Compared with group S, the serum concentrations of S100β and NSE increased significantly, hippocampal tissue was edematous, the cell arrangement was disorder and sparse, the expression levels of cleaved caspase-3 and p-NR2A Y1325 were up-regulated, and the time spent in the target quadrant decreased in group I and group N (P＜0.05). Compared with group I, the serum concentrations of S100β and NSE decreased significantly, morphological changes of hippocampal tissue were ameliorated, the expression levels of cleaved caspase-3 and p-NR2A Y1325 were down-regulated, and the time spent in the target quadrant increased in group N (P＜0.05). There were no significant differences in the expression level of NR2A and escape latency between the three groups (P＞0.05). Conclusion Hepatic ischemia reperfusion could induce brain injury and long-term cognitive dysfunction in young mice, and the mechanism may be associated with the excitotoxicity mediated by excessive phosphorylation of NR2A Y1325.

Key words:  liver, reperfusion injury, hippocampus, receptors, N-methyl-D-aspartate, cognition, mice, inbred C57BL