lithium-chloride and Stroke

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.. 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.. 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.. 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.

Topics: Animals; Brain Injuries; Brain Ischemia; Humans; Infarction, Middle Cerebral Artery; Ischemia; Lithium Chloride; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Stroke

A number of potential interactions between angiotensin-converting enzyme inhibitors and lithium have been described in the literature. In the present study, we investigated the effects of a low-dose combination treatment with lithium and captopril on survival and stroke prevention in salt-loaded, stroke-prone spontaneously hypertensive rats (SHRSP).. Eight-week-old saline-drinking SHRSP (n = 21 per group) were treated with vehicle, LiCl (1 mmol/kg per day), captopril (25 mg/kg per day) and captopril plus LiCl for up to 37 weeks. Body weight, salt water intake blood pressure and mortality were recorded throughout the experimental period. Plasma renin activity, plasma lithium concentration and urinary excretion of albumin, sodium and potassium were measured at different time points.. Captopril treatment doubled the life expectancy when compared with vehicle-treated rats. Lithium alone had minor effects on survival but led to a dramatic increase in survival when added to captopril (mean survival time > 237 versus 147 days, P < 0.001). Systolic blood pressure increased with age in all treatment groups but was comparable in the captopril-treated and the captopril-plus-lithium-treated groups. Plasma renin activity as well as urinary sodium and potassium excretion did not differ between both groups. In the captopril group a striking fivefold increase of albuminuria occurred between 14 and 26 weeks of age, while this progression was completely abolished by the addition of lithium.. Our results demonstrate that the addition of lithium to captopril dramatically prolong the effects of the angiotensin-converting enzyme inhibitor on survival in salt-loaded SHRSP. This effect was independent of a reduction in blood pressure.

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Captopril; Hypertension; Lithium; Lithium Chloride; Male; Potassium; Rats; Rats, Inbred SHR; Renin; Sodium; Sodium, Dietary; Stroke