Anodal Transcranial Direct Current Stimulation Reduces Neuroinflammation and Cholinergic Dysregulation After Young Adult Traumatic Brain Injury

Traumatic brain injury (TBI) during childhood and adolescence can result in persistent motor and cognitive dysfunction due to secondary injury cascades involving neuroinflammation and disruption of neurotransmitter homeostasis. Although transcranial Direct Current Stimulation (tDCS) is a promising non-invasive neuromodulatory intervention, its effects on neuroinflammatory and cholinergic responses following young adult TBI remain incompletely understood. We investigated the effects of anodal and cathodal tDCS on functional outcomes, neuroinflammatory responses, and cholinergic regulatory markers following experimental young adult TBI. Two-month-old male Wistar rats underwent diffuse TBI using the Marmarou weight-drop model and were assigned to Sham, TBI, TBI + anodal tDCS, or TBI + cathodal tDCS groups. tDCS (1 mA, 30 min/day) was initiated 2 h post-injury and applied for 7 consecutive days. Functional outcomes were evaluated using the Open Field, Novel Object Recognition, and Y-maze tests. Neuroinflammatory responses were assessed by measuring tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) levels in the hippocampus and motor cortex using ELISA. Cholinergic regulatory changes were evaluated by analyzing acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) protein expression using Western blotting. Young adult TBI induced significant locomotor and cognitive deficits, accompanied by increased TNF-α and IL-1β levels and alterations in AChE and ChAT expression in the hippocampus and motor cortex. Anodal tDCS significantly improved locomotor activity, recognition memory, and spatial working memory, while attenuating trauma-associated elevations in pro-inflammatory cytokines and reducing TBI-associated alterations in cholinergic regulatory markers. In contrast, cathodal tDCS produced limited behavioral and molecular effects. The effects of anodal stimulation were observed across both the hippocampus and motor cortex, suggesting coordinated modulation of neuroinflammatory and cholinergic responses. Collectively, these findings indicate that early anodal tDCS is associated with improved functional outcomes and modulation of neuroinflammatory and cholinergic responses following young adult TBI. These results support further investigation of anodal tDCS as a potential neuromodulatory approach for promoting recovery after TBI.