Brain injury and neurogenesis after intracerebral haemorrhage in hypertensive rats

Abstract

INTRODUCTION: Effective treatments for intracerebral haemorrhage (ICH) are awaited to reduce its morbidity and mortality. Hypertension is the most important risk factor for ICH. Neurogenesis following ICH in nomotensive rats has been confirmed. In this study, we used a rat renovascular hypertension (RVHT) model, and investigated the effects of hypertension on the pathophysiological and histological changes, and neural stem cell proliferation after induction of ICH. METHODS: RVHT was achieved by applying a silver clip onto the left renal artery. At 6 weeks after renal artery constriction, the mRNA levels of angiogensin II type 1 (AT1) and type 2 (AT2) receptors in the brain were determined by reverse transcription–polymerase chain reaction. ICH was induced by an intrastriatal injection of bacterial collagenase IV in the left brain in both normotensive and hypertensive rats. Left femoral artery was cannulated for continuous monitoring of blood pressure for 4 hours after the induction of ICH. Haematoma volume was quantified at 24 hours after ICH induction. 5’-Bromo-2’-deoxyuridine (BrdU) was used to label cell proliferation from the 6th day to the 9th day after ICH. Rats were killed at 10 days after ICH. BrdU+ and CD31 (an endothelial cell marker) immunoreactive cells were detected using immunofluorescence. Behavioural tests were performed at 1, 3, 7, 10, and 21 days after ICH. RESULTS: RVHT rats showed up-regulation of AT1 receptor in the brain. Following induction of ICH, both the normotensive and RVHT rats demonstrated an acute hypertensive response. As compared to normotensive rats, RVHT rats demonstrated a larger haematoma volume, and greater deficits at all time-points. However, at 10 days after ICH, more BrdU+ cells were detected over the perihaematoma area of RVHT rats than normotensive rats. Moreover, many BrdU+ cells within the ipsilateral basal ganglia of RVHT rats also co-expressed CD31. CONCLUSION: Renovascular hypertension aggravates histological and functional injury partly via up-regulation of AT1 receptor in the brain. Increased brain injury in hypertensive rats induces increased neural stem cell proliferation and angiogenesis after ICH. Experimental ICH in hypertensive rats is a suitable model for evaluation of pathophysiology and treatment of patients with hypertensive ICH.