Lithium chloride promotes neural functional recovery after local cerebral ischemia injury in rats through Wnt signaling pathway activation.

Lithium chloride (LiCl) has a significant neuroprotective effect in cerebral ischemia. However, to date, there is a paucity of evidence on the role of LiCl in neural restoration after brain ischemia and the signaling pathways involved remain unclear. Therefore, to address this gap, the middle cerebral artery occlusion (MCAO) rat model was used to simulate human ischemia stroke. Male SD rats were given MCAO for 90 min followed by reperfusion, and Dickkopf-1(DKK1, 5.0 μg/kg) was administered half an hour before MCAO. Rats were then treated with hypodermic injection of LiCl (2.0 mmol/kg) twice a day for one week. After treatment, cognitive impairment was assessed by the Morris Water Maze test. Neurological deficit score, 2,3,5-triphenyl tetrazolium chloride (TTC) staining, brain water content, and histopathology were used to evaluate brain damage. Enzyme-linked immunosorbent assay was used to measure oxidative stress damage and inflammatory cytokines. Apoptosis of the hippocampal neurons was tested by Western blot. The key factors of Wnt signaling pathway in the ischemic penumbra were detected by immunofluorescence (IF) staining and quantitative real-time polymerase chain reaction (qRT-PCR). Current experimental results showed that LiCl treatment significantly improved the impaired spatial learning and memory ability, suppressed oxidative stress, inflammatory reaction, and neuron apoptosis accompanied by attenuating neuronal damage, which subsequently decreased the brain edema, infarct volume and neurological deficit. Furthermore, the treatment of LiCl activated Wnt signaling pathway. Interestingly, the aforementioned effects of LiCl treatment were markedly reversed by administration of DKK1, an inhibitor of Wnt signaling pathway. These results indicate that LiCl exhibits neuroprotective effects in focal cerebral ischemia by Wnt signaling pathway activation, and it might have latent clinical application for the prevention and treatment of ischemic stroke.