Effects of acute biperiden treatment following traumatic brain injury in male rats.

Traumatic brain injury (TBI) remains a leading cause of morbidity and mortality, with no effective treatments available. Biperiden, a muscarinic receptor antagonist, has demonstrated beneficial 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 h post-injury, followed by two additional doses at 8-hour intervals. Brain and blood were collected twenty-four hours after TBI for, histological, immunohistochemical, and Single Molecule Array (SIMOA) analyses. Results revealed that biperiden-treated (TBI-BIP) rats exhibited diminished degenerating neurons, lower T-tau and NfL levels, decreased astrocyte activation, and restored microglia morphology compared to saline-treated (TBI-SAL) rats, attenuating TBI-induced damage. Motor deficits were most pronounced on Day 1 post-trauma, with non-significant statistical difference in neuroscore performance between the TBI groups, however the biperiden treatment modulates astrocyte reactivity, diminish gliosis, and promote a neuroprotective phenotype. Additionally, biperiden preserves microglial branching following injury. These findings demonstrate that biperiden exerts beneficial effects during the acute phase of TBI by decreasing neuronal degeneration, excitotoxicity, and inflammation, highlighting its therapeutic potential for post-TBI intervention.