Pathophysiological mechanisms in subarachnoid haemorrhage : a study of the neuropharmacological, physiological and morphological changes that occur in a model of subarachnoid haemorrhage developed in the laboratory rat

• Main Author: Jackowski, Andre
• Format: Dissertation
• Language: English
• Published: University of London 1990

This thesis reviews current knowledge regarding the problems created by, possible causal factors, and present management of the disordered pathophysiology that may arise following subarachnoid haemorrhage (SAH) in man. Mechanisms responsible for the normal regulation of the cerebral vasculature are also reviewed. The present investigation explores how various neuropharmacological, physiological and morphological aspects of the major cerebral arteries are affected by such haemorrhage in a small animal model of experimental SAH developed in the laboratory rat. Preliminary immunohistochemical studies revealed that contrary to earlier reports, the extraparenchymal cerebral arteries do not receive a significant serotonergic innervation. Serotonin was only rarely present under normal circumstances in the neural plexus, and when found was invariably contained within nerves also identified as catecholaminergic in nature. Following SAH, major alterations in the neurotransmitter content of the cerebrovasculature occurred. The perivascular sympathetic nerves of major cerebral vessels rapidly accummulated serotonin, while a coincident depletion of neuropeptide Y took place. Using cortically implanted platinum-wire microelectrodes, with measurement of cerebral blood flow (CBF) by hydrogen-clearance, the timecourse of the global reduction in CBF that develops acutely in this model was documented. A 50% reduction in blood flow persisted for up to 3 hours posthaemorrhage, at 24 hours this was restored to 85% of normal, and recovered fully by 48 hours. The fall in CBF developed independently of concommitant changes in intracranial and cerebral perfusion pressure, and it would appear likely that early vasospasm secondary to released blood products, rather than pressure changes per-se, is responsible for the acute cerebral ischaemia that develops. Electron microscopic studies, demonstrated the delayed development of a mild cerebral vasculopathy, comprising focal areas of subintimal medial necrosis. Transformation of cells derived from the pia-arachnoid into macrophages, occurred on the second day post haemorrhage. These cells were then largely responsible for a rapid phagocytic removal of the subarachnoid blood clot. Previous findings obtained by workers using experimental models of SAH are reviewed, and suggestions as to the nature and aetiology of delayed cerebral ischaemia and vasospasm arising after SAH deduced.