Abstract
Infarct size is associated with stroke severity in clinical studies, so reducing it has become an important target and research hotspot in the treatment of ischemic stroke. Some preclinical studies have shown transcranial direct current stimulation (tDCS) reduced infarct size and improved neurological deficit, but others have not found beneficial effects. Besides, the optimal pattern of tDCS for ischemic stroke remains largely unknown. To shed light on the current circumstance and future research directions, the systematic review evaluated the effect of different tDCS paradigms in reducing infarct size and improving neurological deficit in rodent models of ischemic stroke and assessed the methodological quality of current literature. We searched the MEDLINE (via PubMed), EMBASE, Web of Science, and Scopus from their inception to August 18, 2021, to identify studies evaluating the effects of tDCS in rodent models of ischemic stroke. Eight studies were included, of which seven studies were included in the meta-analysis. The results showed cathodal tDCS, rather than anodal tDCS, reduced infarct size mainly measured by tetrazolium chloride and magnetic resonance imaging (standardized mean difference: −1.13; 95% CI: −1.72, −0.53; p = 0.0002) and improved neurological deficit assessed by a modified neurological severity score (standardized mean difference: −2.10; 95% CI: −3.78, −0.42; p = 0.01) in an early stage of focal ischemic stroke in rodent models. Subgroup analyses showed effects of cathodal tDCS on infarct size were not varied by ischemia duration (ischemia for 1, 1.5, and 2 h or permanent ischemia) and anesthesia (involving isoflurane and ketamine). The overall quality of studies included was low, thus the results must be interpreted cautiously. Published studies suggest that cathodal tDCS may be a promising avenue to explore for augmenting rehabilitation from focal ischemic stroke. Considering the methodological limitations, it is unreliable to blindly extrapolate the animal data to the clinical practice. Future research is needed to investigate the mechanism of tDCS in a randomized and blinded fashion in clinically relevant stroke models, such as elderly animals, female animals, and animals with comorbidities, to find an optimal treatment protocol.
Highlights
Stroke, a leading cause of mortality, leads to over two million new cases annually and is associated with the highest disabilityadjusted life-years lost of any disease in China (Guan et al, 2017; Wu et al, 2019)
In the present meta-analysis, we focus on different transcranial direct current stimulation (tDCS) paradigms, with the primary objective being to evaluate the effect of different tDCS paradigms in reducing infarct size and improving neurological deficit from focal ischemic stroke in rodent models
The final literature search was completed on August 18, 2021, to identify studies evaluating the effects of tDCS in rodent models of ischemic stroke, using the following electronic bibliographic databases: MEDLINE, EMBASE, Web of Science, and Scopus
Summary
A leading cause of mortality, leads to over two million new cases annually and is associated with the highest disabilityadjusted life-years lost of any disease in China (Guan et al, 2017; Wu et al, 2019). Reducing infarct size should be an important part of ischemic stroke treatment. Non-invasive tDCS is the process of delivering a weak electric direct current through the scalp to benefit from its cortical excitability modifying effect. It modulates cortex excitability mainly by affecting the membrane polarity. The effect of tDCS may be related to the molecular mechanisms of promoting ischemic tolerance, neuroprotection, neurogenesis, angiogenesis, and antiapoptosis, which may reduce inflammation, edema, or infarct size and improve neurological deficit following ischemic stroke. Previous studies have investigated the effect of tDCS on infarct size and neurological deficit, but results have been inconsistent (Kim et al, 2010; Notturno et al, 2014). No meta-analysis has evaluated the neuroprotective effect of tDCS following ischemic stroke
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