Molecular pathogenesis of subarachnoid haemorrhage

Zhang, Baiping, Fugleholm, Kaare, Day, Lorna B., Ye, Shu, Weller, Roy O. and Day, Ian N.M. (2003) Molecular pathogenesis of subarachnoid haemorrhage. International Journal of Biochemistry & Cell Biology, 35 (9), 1341-1360. (doi:10.1016/S1357-2725(03)00043-8).

Abstract

Subarachnoid haemorrhage (SAH) results from leakage of blood into the subarachnoid space and carries high morbidity and mortality. However, there is limited understanding to date, of the risk factors, cellular, intermediate biochemical and genetic traits predisposing to SAH. Nevertheless, in conjunction with improved methods of diagnostic imaging and less invasive approaches to preventing aneurysmal rupture, there may be utility in gaining a better understanding of the pathogenesis and in identifying pre-disease markers. Additionally, it is not impossible that drugs of value (e.g. matrix or endothelial modifiers) could become available. Several different clinical subtypes can be recognised, distinguished by arterial or venous involvement, presence of unruptured arterial aneurysms, and apparently ‘sporadic’ and ‘familial’ occurrences. Epidemiological risk factors include alcohol consumption and smoking: hypertension is a risk factor for rupture. About 10% seem to reflect strong family history and this subset may be particularly illuminating with respect to the molecular pathogenesis. Haemodynamic stress and poor vascular structure may be the main mechanisms of pathogenesis. The epidemiological and statistical evidence for familial megaphenic genes and modifier genes is reviewed. This review focuses on the pathogenesis, as opposed to inflammatory response to SAH. It sets in context the roles of specific genes and their protein products, such as polycystin (PKD1), fibrillin (FBN1), collagen III (COL3A1), elastin (ELN), collagen IV, protease inhibitor or ?1-antitrypsin (PI) and proteases. These considerations illustrate the shortfalls in current knowledge, the needs of future biochemical and cellular research and their potential implications for future prevention of this often fatal condition.

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