NEUROPROTECTIVE EFFECTS OF COMBINED LYCOPENE AND PRIMIDONE IN A WEIGHT-DROP MOUSE MODEL OF TRAUMATIC BRAIN INJURY: MODULATION OF OXIDATIVE STRESS AND NEUROTRANSMITTER HOMEOSTASIS

Abstract

Background: Traumatic brain injury triggers a multifaceted secondary damage cascade characterized by oxidative/nitrosative stress, excitotoxicity, and neurotransmitter dysregulation, resulting in enduring neurological impairments. Few effective therapies address these interrelated processes. Lycopene, a powerful antioxidant, and primidone, an anticonvulsant with neurostabilizing properties, present a rational combinatorial strategy.

Objective: To assess the individual and combined neuroprotective effects of Lycopene and repurposed Primidone on behavioral, biochemical, and neurotransmitter changes generated by TBI.

Methods: Traumatic brain injury was generated in mice utilizing a weight-drop technique. Animals received lycopene, Primidone, or a combination 30 minutes after injury. Behavioral evaluations were performed at 24 hours and on day 7, followed by biochemical tests of antioxidant enzymes (SOD, CAT, GSH), lipid peroxidation, nitrosative stress, cerebral edema, blood-brain barrier integrity, and neurotransmitters (GABA, glutamate, dopamine, serotonin, AChE).

Results: Traumatic brain injury induced significant behavioral impairments, oxidative and nitrosative stress, neurotransmitter dysregulation, and blood-brain barrier disruption (p<0.001 compared to control). Lycopene and Primidone monotherapy resulted in partial enhancement of these measures (p<0.05 compared to vehicle). Combination treatment yielded markedly enhanced neuroprotection (p<0.01 compared to monotherapy), reinstating antioxidant defenses, diminishing lipid peroxidation and nitrosative stress, resetting neurotransmitter equilibrium, and lowering cerebral edema. These effects continued or were enhanced on day 7.

Conclusion: The combination of Lycopene and Primidone treatment offers improved and prolonged neuroprotection in traumatic brain injury by addressing redox imbalance and neurotransmitter dysregulation, hence endorsing a multi-target therapeutic approach with translational promise.