Experimental study of expression of hypoxia-inducible factor-1α and its role in traumatic brain injury

Abstract

Decades of traumatic brain injury (TBI) research have not led to the development of novel drugs that successfully improve the outcome of injured patients. Thus, new research approaches or medicine are required. Vascular injury is the primary key event that can cause a range of secondary injury, and become a key part of TBI repairmen. Reduced blood flow is one pathophysiological symptom of TBI. Regenerative mechanisms are then initiated to reduce cellular damage, including the activation of hypoxia-inducible transcription factor 1 (HIF-1). Successful revascularization can provide critical neurovascular microenvironment, which produces effective perfusion to promote nerve repair and growth by clearing Toxic factors, providing nutrition, and making it a critical treatment for TBI. Ninety-six male SD rats were divided into four groups: sham group ( n = 8), control (sham operate, n = 8), traumatic brain injury group (TBI group, n = 40) and TBI treated with 2ME2 group ( n = 40). Feeney's method was applied to establish TBI model. At the time point 6 h, 24 h, 3d, 7d, 14d after modeling, the expression of PHD2/HIF-1α/VEGF/Ang-1 were observed by RT-PCR\Western blot analysis. Compared with sham-operated controls, the expression of HIF-1α in TBI group have been significantly ( P < 0.05) enhanced, which related to the degradation of PHD2 following TBI induction. HIF-1α expression began to increase after 6 h, within 24 h to 3d reached peak and fall to common levels before 7d. Nevertheless, VEGF/Ang-1 expression was remarkably ( P < 0.01) decreased after inhibition of HIF-1α by 2-ME-2. The expression of HIF-1α increased after experimental TBI, which can induce its downstream target gene expression to promote the repairment of injured vascular and angiogenesis.