Cathodal-transcranial direct current stimulation induces therapeutic effects in animal ischemia models by preventing the expansion of ischemic injury during the hyperacute phase of ischemia. However, its efficacy is limited by an accompanying decrease in cerebral blood flow. On the other hand, peripheral sensory stimulation can increase blood flow to specific brain areas resulting in rescue of neurovascular functions from ischemic damage. Therefore, the two modalities appear to complement each other to form an integrated treatment modality. Our results showed that hemodynamics was improved in a photothrombotic ischemia model, as cerebral blood volume and hemoglobin oxygen saturation (SO2) recovered to 71% and 76% of the baseline values, respectively. Furthermore, neural activities, including somatosensory-evoked potentials (110% increase), the alpha-to-delta ratio (27% increase), and the (delta+theta)/(alpha+beta) ratio (27% decrease), were also restored. Infarct volume was reduced by 50% with a 2-fold preservation in the number of neurons and a 6-fold reduction in the number of active microglia in the infarct region compared with the untreated group. Grip strength was also better preserved (28% higher) compared with the untreated group. Overall, this nonpharmacological, nonintrusive approach could be prospectively developed into a clinical treatment modality.
Current treatments for ischemic stroke have focused on the administration of a tissue plasminogen activator, although the associated side effects and subsequent reperfusion injury remain challenging. Peripheral electrical stimulation has shed light on therapeutic interventions for ischemia by increasing cerebral blood flow (CBF) to the target region through collateral circulation, although the mechanism remains elusive. Here, a focal photothrombotic ischemic (PTI) stroke was induced in the right hemispheric primary somatosensory forelimb cortex (S1FL) of rat brains, and the therapeutic effects of forelimb and hindlimb stimulation were characterized at the contralesional S1FL. We observed that PTI stroke rats that received forelimb stimulation exhibited significantly restored CBF of the ischemic penumbra (1.06±0.25 for the S1FL and 0.99±0.14 for the primary somatosensory hindlimb cortex, respectively), electrocorticography (ECoG) delta band coherence of the intercortical S1FL (0.93±0.04) at the 75th min poststroke and an ischemic infarct (7.3±0.2 mm3) via collateral circulation recruitment. Importantly, anterior cerebral artery/middle cerebral artery (ACA–MCA) interarterial anastomotic regulation occurred upon forelimb stimulation and played roles in the recovery of neurovascular functions. These results indicated that receptive field-specific stimulation further restores CBF, neuronal activities, and tissue viability through the enhancement of ACA–MCA interarterial anastomosis-mediated collateral circulation and provides a feasible therapeutic intervention for stroke recovery.
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