Neuroprotective mechanism of syringic acid targeting oxidative damage and neuroinflammation in an experimental model of traumatic brain injury.

BACKGROUND

Traumatic brain injury (TBI) is a complex neurological condition, with accumulating evidence highlighting the critical roles of neuroinflammation and oxidative stress in its pathogenesis. In this context, the present study has been designed to evaluate the neuroprotective mechanism of syringic acid, both individually and in combination with minocycline, against trauma-induced behavioural and biochemical impairments in a rat model of experimental brain injury.

MATERIAL AND

METHODS

Male Sprague-Dawley (SD) rats were undergone traumatic brain injury by the weight dropped method. Following the induction of traumatic brain injury and a subsequent two-week recovery period with syringic acid and minocycline administered either individually or in combination, for an additional two weeks. During the treatment phase, a series of behavioural assessments, including body weight monitoring, evaluation of locomotor activity, motor coordination, anxiety-like behaviour (via the elevated plus maze), and memory performance at different time intervals, were conducted to assess functional recovery. These were followed by biochemical evaluations of oxidative and antioxidant markers, mitochondrial enzyme complexes activities, acetylcholinesterase (AChE) levels, and TNF-α were evaluated in specific brain regions.

RESULTS

TBI significantly reduced body weight and caused marked impairment in locomotor, motor coordination, memory performance, and anxiety-like behaviour. While also inducing blood-brain barrier disruption, cerebral edema, elevated TNF-α and AchE levels, and attenuating oxidative defence mechanisms and mitochondrial enzyme complex activities in discrete areas (cortex and hippocampus) of the brain, compared to the sham group. Treatment with syringic acid (25, 50, and 100 mg/kg) and minocycline (25 mg/kg) for 14 days significantly improved the behavioural and reversed biochemical impairments as compared to control group (TBI), which was comparable to that of salicylic acid (150 mg/kg). Further, the combination of syringic acid (25 mg/kg) with minocycline (25 mg/kg) treatment for 14 days demonstrated a significant neuroprotective effect as compared to their effect per se, suggesting a potential synergistic effect.

CONCLUSION

The current study demonstrates the involvement of microglial inhibitory mechanisms in the neuroprotective effect of syringic acid in an experimental model of TBI. The study highlights that the syringic acid in combination with minocycline could be used effectively against traumatic brain damage.