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Cathodal tDCS exerts neuroprotective effect in rat brain after acute ischemic stroke.

ABSTRACT: BACKGROUND:Transcranial direct current stimulation (tDCS) is a non-invasive brain modulation technique that has been proved to exert beneficial effects in the acute phase of stroke. To explore the underlying mechanism, we investigated the neuroprotective effects of cathodal tDCS on brain injury caused by middle cerebral artery occlusion (MCAO). RESULTS:We established the MCAO model and sham MCAO model with an epicranial electrode implanted adult male Sprague-Dawley rats, and then they were randomly divided into four groups (MCAO?+?tDCS, MCAO?+?sham tDCS (Sham), Control?+?tDCS and Control?+?Sham group). In this study, the severity degree of neurological deficit, the morphology of brain damage, the apoptosis, the level of neuron-specific enolase and inflammatory factors, the activation of glial cells was detected. The results showed that cathodal tDCS significantly improved the level of neurological deficit and the brain morphology, reduced the brain damage area and apoptotic index, and increased the number of Nissl body in MCAO rats, compared with MCAO?+?Sham group. Meanwhile, the high level of NSE, inflammatory factors, Caspase 3 and Bax/Bcl2 ratio in MCAO rats was reduced by cathodal tDCS. Additionally, cathodal tDCS inhibited the activation of astrocyte and microglia induced by MCAO. No difference was found in two Control groups. CONCLUSION:Our results suggested that cathodal tDCS could accelerate the recovery of neurologic deficit and brain damage caused by MCAO. The inhibition of neuroinflammation and apoptosis resulted from cathodal tDCS may be involved in the neuroprotective process.

SUBMITTER: Zhang KY

PROVIDER: S-EPMC7216334 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Cathodal tDCS exerts neuroprotective effect in rat brain after acute ischemic stroke.

Zhang Ke-Ying KY Rui Gang G Zhang Jun-Ping JP Guo Ling L An Guang-Zhou GZ Lin Jia-Jin JJ He Wei W Ding Gui-Rong GR

BMC neuroscience 20200512 1

<h4>Background</h4>Transcranial direct current stimulation (tDCS) is a non-invasive brain modulation technique that has been proved to exert beneficial effects in the acute phase of stroke. To explore the underlying mechanism, we investigated the neuroprotective effects of cathodal tDCS on brain injury caused by middle cerebral artery occlusion (MCAO).<h4>Results</h4>We established the MCAO model and sham MCAO model with an epicranial electrode implanted adult male Sprague-Dawley rats, and then ...[more]

PMID: 32397959

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Project description:ImportanceCathodal transcranial direct current stimulation (C-tDCS) provides neuroprotection in preclinical models of acute ischemic stroke (AIS) by inhibiting peri-infarct excitotoxic effects and enhancing collateral perfusion due to its vasodilatory properties.ObjectiveTo report the first-in-human pilot study using individualized high-definition (HD) C-tDCS as a treatment of AIS.Design, setting, and participantsThis randomized clinical trial was sham controlled with 3 + 3 dose escalation design, and was conducted at a single center from October 2018 to July 2021. Eligible participants were treated for AIS within 24 hours from onset, had imaging evidence of cortical ischemia with salvageable penumbra, and were ineligible for reperfusion therapies. HD C-tDCS electrode montage was selected for each patient to deliver the electric current to the ischemic region only. Patients were followed for 90 days.Main outcomes and measuresPrimary outcomes were feasibility, assessed as time from randomization to study stimulation initiation; tolerability, assessed by rate of patients completing the full study stimulation period; and safety, assessed by rates of symptomatic intracranial hemorrhage at 24 hours. The efficacy imaging biomarkers of neuroprotection and collateral enhancement were explored.ResultsA total of 10 patients with AIS were enrolled, 7 were randomized to active treatment and 3 to sham. Patient age was mean (SD) 75 (10) years old, 6 (60%) were female, and National Institutes of Health Stroke Scale score was mean (SD) 8 (7). Two doses of HD C-tDCS (1 milliamp [mA] for 20 minutes and 2 mA for 20 minutes) were studied. The speed of HD C-tDCS implementation was a median (IQR) 12.5 minutes (9-15 minutes) in the last 4 patients. Patients tolerated the HD C-tDCS with no permanent stimulation cessation. The hypoperfused region was reduced by a median (IQR) 100% (46% to 100%) in the active group vs increased by 325% (112% to 412%) in sham. Change in quantitative relative cerebral blood volume early poststimulation was a median (IQR) 64% (40% to 110%) in active vs -4% (-7% to 1%) sham patients and followed a dose-response pattern. Penumbral salvage in the active C-tDCS group was median (IQR) 66% (29% to 80.5%) vs 0% (IQR 0% to 0%) in sham.Conclusion and relevanceIn this randomized, first-in-human clinical trial, HD C-tDCS was started efficiently and well tolerated in emergency settings, with signals of beneficial effect upon penumbral salvage. These results support advancing HD C-tDCS to larger trials.Trial registrationClinicalTrials.gov Identifier: NCT03574038.

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Cathodal tDCS exerts neuroprotective effect in rat brain after acute ischemic stroke.

Publications

Cathodal tDCS exerts neuroprotective effect in rat brain after acute ischemic stroke.

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