Lithium and Stroke Recovery: A Systematic Review and Meta-Analysis of Stroke Models in Rodents and Human Data

Abstract

Background: Lithium has neuroprotective effects in animal models of stroke, but benefits in humans remain uncertain. This article aims to systematically review the available evidence of the neuroprotective and regenerative effects of lithium in animal models of stroke, as well as in observational and trial stroke studies in humans. Methods: This systematic review and meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched Medline, Embase, and PsycINFO for preclinical and clinical studies published between January 2000 and September 2021. A random-effects meta-analysis was conducted from observational studies. Results: From 1625 retrieved studies, 42 were included in the systematic review. Of those, we identified 36 rodent models of stroke using preinsult or postinsult treatment with lithium, and 6 studies were conducted in human samples, of which 4 could be meta-analyzed. The review of animal models was stratified according to the type of stroke and outcomes. Human data were subdivided into observational and intervention studies. Treatment of rodents with lithium was associated with smaller stroke volumes, decreased apoptosis, and improved poststroke function. In humans, exposure to lithium was associated with a lower risk of stroke among adults with bipolar disorder in 2 of 4 studies. Two small trials showed equivocal clinical benefits of lithium poststroke. Conclusions: Animal models of stroke show consistent biological and functional evidence of benefits associated with lithium treatment, whereas human evidence remains sparse and inconclusive. The potential role of lithium in poststroke recovery is yet to be adequately tested in humans.

Effect and mechanisms of resveratrol in animal models of ischemic stroke: A systematic review and Bayesian meta-analysis

“…Beyond trying to reach as much statistical power as possible, there is no rule of thumb about the number of studies required for a meta-analysis. 124 The present study, focusing on ischemic stroke, included a number of primary articles higher than that in a recent systematic review on lithium and stroke recovery in rodent models of both ischemic and hemorrhagic strokes, 125 and a number of animals well above the median (749 [463,1797]) in thirteen previous experimental stroke meta-analyses. 126 In addition to the number of studies, there is their methodological quality.…”

Therapies Targeting Stroke Recovery

“…This includes familiar pharmacological agents; for example, lithium has shown promise in preclinical studies for improving stroke outcome and performed well in 2 early phase trials examining global impairment and cognitive function. 17 In addition, gabapentin, thought to enable axon sprouting and regeneration of white matter pathways, was associated with greater upper limb function when given 1 day after stroke onset in mice. 18 O'Sullivan et al 19 suggest a role for cholinergic medications.…”

Exploring the Neuroprotective Effects of Lithium in Ischemic Stroke: A literature review

“…Individuals with different genotypes may respond differently to lithium treatment 12 , 26 . While experimental models have demonstrated the impact of lithium on ischemic stroke 27 , its mechanism remains incompletely understood 12 . Furthermore, its clinical application is not well-established 27 .…”

“…While experimental models have demonstrated the impact of lithium on ischemic stroke 27 , its mechanism remains incompletely understood 12 . Furthermore, its clinical application is not well-established 27 . In this review, our emphasis is on elucidating the neuroprotective role of lithium against ischemic stroke (Figure 1 ).…”