A potent inhibition of oxidative stress induced gene expression in neural cells by sustained ferulic acid release from chitosan based hydrogel

• C/G/GP–ferulic acid hydrogel to reduce pathological consequences in secondary TBI
• FA laden hydrogel significantly reverted DNA fragmentation & inhibited cell apoptosis.
• First detailed report of FA mediated gene expression in neuronal oxidative stress
• C/G/GP hydrogel could be an ideal carrier to deliver FA during brain injury.

Traumatic brain injury (TBI) is an extremely cataclysmic neurological disorder and the inhibition of oxidative stress following TBI could effectively protect the brain from further impairments. An injectable thermosensitive chitosan/gelatin/β-Glycerol phosphate (C/G/GP) hydrogel for the controlled release of the phenolic antioxidant ferulic acid (FA) to inhibit the neurological oxidative stress was demonstrated. The C/G/GP hydrogel ensures an excellent clinical expediency with a gelation temperature of 32.6 °C and gelation time of 75.58 s. In-vitro cytotoxicity assays of C/G/GP hydrogel and FA have revealed an excellent biocompatibility with the Neuro-2a cells. 500 μM of FA was considered to be an effective concentration to reduce the oxidative stress in Neuro-2a cells. TUNEL staining images evidenced that the H2O2 induced DNA fragmentation was comprehensively controlled after FA treatment. The mRNA gene expression profiles markedly authenticate the neuroprotectivity of FA by down-regulating ROS, inflammatory and apoptosis related markers. The outcomes of this study suggest that, C/G/GP hydrogel carrying ferulic acid could effectively protect further secondary traumatic brain injury associated impairments.

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