Biperiden Hydrochloride

Traumatic brain injury (TBI) disrupts brain function and may lead to post-traumatic epilepsy (PTE), a long-term complication. Anticholinergic drugs, such as biperiden, have shown potential in modulating neural plasticity. This study evaluated whether biperiden treatment influences motor and cognitive recovery, seizure susceptibility, and neurovascular and inflammatory responses in rats subjected to the lateral fluid percussion injury (LFPI) model. Adult male Wistar rats underwent LFPI or sham surgery and were treated with saline or biperiden (8 mg/kg) administered intraperitoneally every 8 h for 10 days, starting 6 h after trauma. Neuromotor battery tests were assessed over 28 days, spatial memory at 30 days using the Barnes Maze, and seizure susceptibility was tested with pentylenetetrazol (PTZ) at 90 days after trauma as a second hit. Plasma samples were collected 10 days after trauma for Single Molecular Array (SIMOA) analysis of trauma biomarkers, neurofilament light chain (NfL), and total tau. Histological and immunofluorescence analyses were conducted at 91 days. TBI significantly increased plasma NfL levels compared to the Naive group, indicating neuronal damage. Animals that underwent LFPI and were treated with saline solution were called TBI-SAL group, while animals that underwent LFPI and were treated with biperiden solution were called TBI-BIP group. TBI-SAL group exhibited memory impairments and random search strategies in the Barnes Maze. Both TBI groups (those treated with saline and with biperiden) exhibited higher seizure susceptibility to PTZ at 30 mg/kg, but biperiden slightly reduced seizure intensity. Histological analyses revealed larger lesion volumes, reduced NeuN expression in hippocampal regions (CA1, CA3), and altered astrocytic and microglial morphology in the TBI-SAL group. Notably, biperiden treatment promoted vascular remodeling, characterized by an increase in vessel density, in the motor cortex and hippocampal regions, suggesting potential modulation of post-traumatic neuroinflammation. Biperiden enhanced vascular remodeling and partially mitigated long-term histopathological changes after TBI, though its protective effects on cognitive and seizure-susceptibility responses were limited. These findings highlight biperiden's potential to influence vascular and inflammatory responses in the injured brain.