HIPK۲ protects neurons from oxidative stress and modulates central nervous system responses following traumatic brain injury

Objective(s): Traumatic brain injury (TBI) induces oxidative stress, contributing to secondary neuronal damage. This study aimed to elucidate the role of the stress-responsive kinase HIPK۲ in regulating endogenous antioxidant defenses in neural tissue following TBI.Materials and Methods: We employed complementary in vitro and in vivo models: an H₂O₂-induced oxidative stress model in PC۱۲ cells (with HIPK۲ inhibited by tBID) and a controlled cortical impact mouse model of TBI (with HIPK۲ overexpressed via intracerebroventricular Ad-HIPK۲ injection). Analyses included assessments of cell viability, mRNA expression, and protein levels of key antioxidant factors (HO-۱, UGT۱A۱, NQO۱).Results: In vitro, HIPK۲ inhibition markedly increased oxidative stress-induced cell death and significantly down-regulated UGT۱A۱ expression. In vivo, endogenous HIPK۲ expression was significantly suppressed post-TBI. Conversely, HIPK۲ overexpression effectively rescued the expression of antioxidant proteins UGT۱A۱ and NQO۱. Conclusion: These results demonstrate that HIPK۲ is a critical modulator of the antioxidant response after TBI, capable of orchestrating key defense genes and conferring neuroprotection. Our findings identify HIPK۲ as a promising molecular target for therapeutic intervention against TBI-related oxidative damage.

کلیدواژه ها:

Anti-oxidant response ، HIPK۲ ، Neuroprotection ، Oxidative stress ، Traumatic brain injury