Introduction: Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique safe and promising in early human studies of nonacute disorders (depression, OCD, stroke recovery), and also reported to confer direct neuroprotection and vasodilation in animal models of acute cerebral ischemia. Systematic review of preclinical acute cerebral ischemia studies would aid planning for potential initial human clinical trials.
Method: A systematic Medline search identified controlled, preclinical studies of tDCS in acute ischemic stroke. Studies were categorized according to stimulation type (hemispheric cathodal; hemispheric anodal; targeted cerebellar fastigial nucleus). Stratified meta-analysis assessed effect of tDCS on final infarct volume.
Results: The systematic search identified 17 controlled comparisons of tDCS in preclinical acute cerebral ischemia models, including a total of 256 animals, all with middle cerebral artery occlusion. Hemispheric cathodal stimulation was used in 3 experiments (32 animals), hemispheric anodal stimulation in 1 experiment (8 animals) and fastigial nucleus stimulation in 13 experiments (91 animals). Overall, tDCS reduced final infarct volume by 27.5 cc (95% CI 25.33-29.74, P<0.00001). Heterogeneity of effect by stimulation type was noted (I2=90.5%), with the greatest infarct reduction with cathodal - 34.9 cc (95% CI 30.60-39.18, P< 0.00001), followed by targeted fastigial nucleus - 26.8 cc (95% CI 25.33-29.53, P< 0.00001), and anodal - 17.8 cc (95% CI 11.42-24.18, P< 0.00001). In the cathodal studies, stimulation was started 30-45 minutes after ischemia onset.
Conclusions: Transcranial direct current stimulation reduces final infarct volume across animal preclinical studies. The greatest neuroprotective effect is observed with hemispheric cathodal stimulation, with treatment initiation in a time frame achievable in human prehospital clinical trials. Human clinical trials of hemispheric cathodal tDCS are warranted.