Neurovascular and inflammatory effects of biperiden in the acute phase of moderate traumatic brain injury: evidence from a non-human primate model.

Traumatic brain injury (TBI) leads to extensive structural damage, neuronal loss, and functional deficits, along with marked disruption of cholinergic signaling and acute surges in acetylcholine. Biperiden, a muscarinic cholinergic antagonist, has emerged as a potential neuroprotective agent due to its ability to modulate synaptic plasticity and reduce excitotoxicity. Here, we evaluated the acute effects of biperiden in a translational non-human primate model of moderate TBI. Marmosets (Callithrix jacchus,n = 39) subjected to lateral fluid percussion injury (LFPI) received intraperitoneal biperiden (8 mg/kg) beginning 6 h post-injury, followed by two additional doses administered at 8 h intervals. At 24 h post-injury, brain tissue and serum were assessed using histology, immunofluorescence, and Single Molecule Array (SIMOA). Twenty-four hours post-trauma, biperiden treatment reduced hippocampal neuronal degeneration, decreased UCH-L1 levels, and attenuated astrocyte activation compared to saline-treated controls. Although biperiden is a clinically characterized muscarinic antagonist, the direct muscarinic target was not assessed in this primate model. These findings provide preliminary evidence that repeated dosing with biperiden may modulate early neurovascular and glial responses and provide acute neuroprotection following moderate TBI in marmosets, mitigating neuronal injury, excitotoxicity, and inflammation. This work highlights biperiden as a promising therapeutic candidate for early intervention after TBI.