Effects of PPARα Activation and the Role of HO‐1 in Acute SAH‐Induced Fall in Cerebral Blood Flow in Rat

Abstract

Traumatic Brain Injury is a serious public health problem; it is a major cause of death and disability globally resulting from secondary subarachnoid hemorrhage (SAH). We have investigated the effects of PPARα activation and the role of HO‐1 in acute SAH‐induced fall in cerebral blood flow (CBF). Rats received PPARα activator clofibrate, HO‐1 activator (CoCl2) and inhibitor (SnMPP) (2.4 mg; 50 μg, and 24 μg/kg or vehicle) 2–4 days before injection (i.c) of 0.2ml of blood (SAH). Changes in CBF were determined by Laser Doppler Scanner (Moor LDI 5152), the data presented as percentage change in CBF. Clofibrate and CoCl2 increased CBF by 3 and 8% while SnMPP and SAH reduced CBF by 30% and 50% at 15 min. Clofibrate and CoCl2 pretreatments prevented SAH‐induce fall in CBF (−11 and −21%), while SnMPP potentiated the fall in CBF {−70 vs. −50% (SAH)}. SnMPP obliterated clofibrate‐induced attenuation of SAH‐induced fall in CBF (−59% vs. −11%). CoCl2 and Clofibrate treatments increased bilirubin levels in the plasma from 189±30 to 202±35 and 257±28 μM with SnMPP reducing it to 33±5 μM. The CoCl2 and Clofibrate‐induced increases in bilirubin were reduced to 40±10 and 159±30 μM in the presence of SnMPP. Thus, PPARα prevented SAH‐induced fall in CBF, an effects which seems to be mediated via activation of HO‐1 as its inhibitor prevented it. PPARα and HO‐1 signaling pathways could be a viable therapeutic target for the treatment of TBI.