Background: Lithium chloride (LiCl) has a significant neuroprotective effect in
cerebral ischaemia. However, to date, there is a paucity of evidence on the role
of LiCl in neural restoration after brain ischaemia and the signalling pathways
involved remain unclear.
Materials and methods: Therefore, to address this gap, the middle cerebral artery
occlusion (MCAO) rat model was used to simulate human ischaemia stroke. Male
Sprague-Dawley 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 1 week. After treatment, cognitive impairment was assessed by the Morris
water maze test. Neurological deficit score, 2,3,5-triphenyl tetrazolium chloride
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 signalling pathway in
the ischaemic penumbra were detected by immunofluorescence staining and
quantitative real-time polymerase chain reaction.
Results: 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 oedema, infarct volume
and neurological deficit. Furthermore, the treatment of LiCl activated Wnt signalling
pathway. Interestingly, the aforementioned effects of LiCl treatment were markedly
reversed by administration of DKK1, an inhibitor of Wnt signalling pathway.
Conclusions: These results indicate that LiCl exhibits neuroprotective effects in
focal cerebral ischaemia by Wnt signalling pathway activation, and it might have
latent clinical application for the prevention and treatment of ischaemic stroke.