Vindeburnol Induces Neuroprotection in Rat Traumatic Brain Injury via Adrenergic Receptor Antagonism

Traumatic Brain Injury (TBI) causes substantial neurological deficits and remains a major therapeutic challenge. This study aimed to evaluate the neuroprotective properties of Vindeburnol (VIND), a semi-synthetic derivative of vincamine, and to identify its potential molecular targets and optimal dosing regimen for post-traumatic treatment.

Radioligand binding assays were used to determine VIND affinity for 22 CNS receptors, 7 ion channels, and 1 enzyme at a concentration of 10 μM. The in vivo neuroprotective effect was studied in a rat model of TBI induced by controlled cortical impact. VIND was administered intraperitoneally at doses of 10 or 20 mg/kg daily or every other day for 10 days. Neurological recovery was assessed using the beam-walking and limb-placement tests, and brain lesion volume was quantified by MRI on day 14.

VIND showed strong inhibition of radioligand binding at α1- and α2-adrenergic receptors (74% and 84.1%, respectively). In vivo, the most pronounced neuroprotective effect was observed at 20 mg/kg every other day, resulting in approximately a twofold reduction in lesion volume (88.7 ± 6.5 mm3 vs 179.4 ± 19.3 mm3 in saline-treated TBI rats, p < 0.001) and a significant improvement in neurological outcomes. The 10 mg/kg dose showed a non-significant trend towards neuroprotection.

The neuroprotective effect of VIND is likely mediated by the inhibition of excessive adrenergic receptor activation, resulting in improved neuronal survival and functional recovery. These findings highlight adrenergic modulation as a promising therapeutic mechanism for mitigating post-traumatic brain damage.

Vindeburnol demonstrated significant neuroprotective efficacy in a rat model of TBI and may represent a promising pharmacological candidate for post-traumatic neuroprotection.