The potential role of transcranial direct current stimulation in experimental ischemic stroke in adult male albino rats

Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulatory technique with potential therapeutic applications in stroke, but the mechanisms underlying its neuroprotective effects in acute ischemia remain unclear. To evaluate the effects of cathodal versus anodal tDCS on neurobehavioral outcomes, histopathological changes, and inflammatory and glial responses in a rat model of focal cerebral ischemia. Adult male albino rats were randomized into normal non-ischemic, untreated stroke, sham, anodal, and cathodal tDCS groups. Neurological status and sensorimotor function were assessed 24 h after ischemia. Infarct volume (TTC), neuronal integrity (H&E and Nissl), and expressions of TNF-α, c-Fos, CD206, and GFAP were analyzed to characterize neuroinflammation, neuronal activity, and glial responses. Cathodal tDCS improved neurological scores and preserved sensorimotor function compared with anodal, sham, and untreated groups, the latter of which frequently exhibited acute coma. Histopathology in the cathodal group showed reduced necrosis, diminished inflammatory infiltration. In contrast, anodal stimulation produced only partial improvement, remaining significantly less effective than cathodal stimulation. Molecular profiling revealed that cathodal tDCS decreased TNF-α, enhanced astrocytic activation (GFAP) and neuronal activation (c-Fos), and promoted a trend toward M2 microglial polarization (CD206), whereas anodal tDCS exerted weaker effects. Cathodal tDCS conferred superior early neuroprotection and functional recovery after experimental ischemic stroke compared with anodal, sham, and untreated groups, likely through stronger modulation of inflammatory and glial pathways. While anodal stimulation showed limited benefit, cathodal stimulation demonstrated greater translational potential as an acute-phase intervention for ischemic stroke.