Neuroprotective Effects of Acute Biperiden Treatment Following Traumatic Brain Injury in Male Rats

Abstract Traumatic brain injury (TBI) remains a leading cause of morbidity and mortality, with no effective treatments available. Biperiden, a muscarinic receptor antagonist, has demonstrated neuroprotective effects by modulating neural plasticity and reducing excitotoxicity. This study investigated the acute impact of cellular and structural changes in a moderate TBI model using lateral fluid percussion injury (LFPI) in male Wistar rats. Biperiden (8 mg/kg) was administered intraperitoneally at 6 hours post-injury, followed by two additional doses at 8-hour intervals. Brains were collected twenty-four hours after TBI for SIMOA analyses, histological, and immunohistochemical analyses. Results revealed that biperiden-treated (TBI-BIP) rats exhibited fewer degenerating neurons, lower T-tau and NfL levels, reduced astrocyte activation, and partially restored microglia morphology compared to saline-treated (TBI-SAL) rats, suggesting attenuation of TBI-induced damage. Motor deficits were most pronounced on Day 1 post-trauma, with the TBI-BIP group showing a modest but non-significant improvement in neuroscore performance. The treatment appeared to modulate astrocyte reactivity, reducing gliosis and promoting a neuroprotective phenotype. Additionally, biperiden preserves microglial branching following injury. These findings suggest that biperiden exerts protective effects in the acute phase of TBI by reducing neuron degeneration, excitotoxicity, and inflammation, highlighting its therapeutic potential for post-TBI intervention.