Characterising the role of haptoglobin in experimental subarachnoid haemorrhage.

Subarachnoid haemorrhage (SAH) is a devastating event associated with significant mortality and morbidity. A large proportion of SAH patients either die or suffer permanent disability due to a delayed multifactorial injury processes involving blood vessels, diverse inflammatory processes and secondary injury mechanisms. Extracellular haemoglobin (Hb), released from lysed red blood cells after SAH, is thought to be one of the prime culprits that incite these pathological processes. The role of haptoglobin (Hp), a systemic acute phase protein and the primary Hb-scavenging molecule, has recently been postulated to play a role in the pathogenesis of cerebral arterial vasospasm and delayed neurological deterioration in patients suffering SAH. The aim of this project was to demonstrate the relationship between free Hb and Hp within the cerebrospinal fluid following SAH, using the previously validated rat filament model. The results show that whilst free Hb levels peaked at 24hr post-SAH, there was marked free Hb within the CSF as early as the 1hr post-SAH. In addition, there was an increase in CSF Hp and soluble CD163 macrophage haemoglobin scavenger receptor from baseline, concomitant with the Hb peak at the 24hr mark, with a steady and rapid taper off, in keeping with clearance of free Hb by 72hrs post-SAH. Additionally, histological assessment to examine macrophage receptor for uptake and subsequent degradation of the Hb/Hp complex showed sporadic parenchymal staining within the basal brain surface of rats that sustained SAH, but was absent in sham and control animals. This study adds further to the understanding of the way haemoglobin is handled in the central nervous system following SAH.Thesis (M.Phil.) -- University of Adelaide, School of Medical Sciences, 201