TY - JOUR
T1 - Lithium and Stroke Recovery
T2 - A Systematic Review and Meta-Analysis of Stroke Models in Rodents and Human Data
AU - Almeida, Osvaldo P
AU - Singulani, Monique P
AU - Ford, Andrew H
AU - Hackett, Maree L
AU - Etherton-Beer, Christopher
AU - Flicker, Leon
AU - Hankey, Graeme J
AU - De Paula, Vanessa J R
AU - Penteado, Camila T
AU - Forlenza, Orestes V
PY - 2022/9
Y1 - 2022/9
N2 - 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.
AB - 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.
KW - Adult
KW - Animals
KW - Humans
KW - Lithium/pharmacology
KW - Neuroprotective Agents/pharmacology
KW - Observational Studies as Topic
KW - Rodentia
KW - Stroke/drug therapy
U2 - 10.1161/STROKEAHA.122.039203
DO - 10.1161/STROKEAHA.122.039203
M3 - Article
C2 - 35968702
SN - 0039-2499
VL - 53
SP - 2935
EP - 2944
JO - Stroke
JF - Stroke
IS - 9
ER -