Impaired Expression of Neuroprotective Molecules in the HIF-1α Pathway following Traumatic Brain Injury in Aged Mice

Abstract Elderly traumatic brain injury (TBI) patients have higher rates of mortality and worse functional outcome than non-elderly TBI patients. The mechanisms involved in poor outcomes in the elderly are not well understood. Hypoxia-inducible factor–1 alpha (HIF-1α) is a basic helix-loop-helix transcription factor that modulates expression of key genes involved in neuroprotection. In this study, we studied the expression of HIF-1α and its target survival genes, heme oxygenase–1 (HO-1), vascular endothelial growth factor (VEGF), and erythropoietin (EPO) in the brains of adult versus aged mice following controlled cortical impact (CCI) injury. Adult (5–6 months) and aged (23–24 months) C57Bl/6 mice were injured using a CCI device. At 72 h post-injury, mice were sacrificed and the injured cortex was used for mRNA and protein analysis using real-time reverse transcription—polymerase chain reaction (RT-PCR) and Western blotting protocols. Following injury, HIF-1α, HO-1, and VEGF showed upregulation in both t...