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Title: The characterization of altered cerebrovascular homeostasis associated with background pathology and its influence upon haemodynamic responsiveness in a rodent model of haemorrhagic stroke
Author: Fouyas, Ioannis Panayiotou
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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The aims of this thesis were (i) to investigate whether cerebrovascular dysfunction linked to a perturbation of nitric oxide (NO)-related control mechanisms, is associated with IDDM and chronic hypertension; (ii) to assess the extent to which any abnormal cerebrovascular physiology associated with IDDM and chronic hypertension contributes to pathophysiology following haemorrhagic stroke; and finally (iii) to determine if endothelin (ET) or neuronally derived NO, which may be implicated in the development of delayed perilesional ischaemia following ICH in normal animals, potentiate the ischaemic burden following experimental ICH in diabetic or hypertensive animals respectively. Physiological studies revealed that both IDDM and chronic hypertension are associated with NO-dependent cerebrovascular dysfunction. IDDM is associated with a reduced basal LCBF, linked to specific perturbation of endothelial NO, but with an intact NO-related vasodilatory capacity. In contrast, chronic hypertension is associated with an attenuated NO-associated vasodilatory reserve, in conjunction with a upregulated neuronal NO system. The haematoma studies revealed that the presence of intraparenchymal blood, rather than the mass effect, is responsible for the evolution of delayed perilesional oligaemia, which in turn is exacerbated by the presence of diabetes mellitus. Finally, although the endothelin antagonist and the neuronally derived NOS inhibitor resulted in haemodynamic improvement in the non-diseased animals, both the diabetic and hypertensive rats exhibited resistance to their beneficial effect. In conclusion, there is abnormal cerebrovascular homeostasis associated with IDDM and chronic hypertension resulting in worse outcome following experimental haemorrhagic stroke. This cerebrovascular pathology results in resistance to neuroprotection with endothelin antagonists or neuronal NOS inhibitors which are effective in healthy animals. These results are of particular importance since stroke commonly occurs in patients with assorted "risk" factors that can cause underlying alterations in cerebrovascular regulation. Extrapolation of the neuroprotective strategies that have evolved from tests in young healthy animals may therefore be inappropriate.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available