Stroke is defined as an acute neurological deficit resulting from vascular infarction or haemorrhage within the central nervous system. Affecting 13.7 million people annually, stroke is the second leading cause of death and acquired disability globally. In Ireland, 7500 strokes are recorded per year representing the leading cause of acquired neurological disability worldwide (1-2).
The pathogenesis of stroke can be separated into haemorrhagic or ischaemic. Ischaemic strokes describe vessel constriction or occlusion in the brain, responsible for 85% of all cases. Treatments such as thrombolytics (Alteplase/Tenecteplase) and thrombectomy focus on occlusion removal and blood flow restoration. There is urgency in recanalization to preserve neurological function and to optimise recovery time and quality of life (3).
This investigation will be informed by the ‘RESTORE’ registry managed by Prof. Doyle, which has accumulated over 1,000 acute ischaemic stroke (AIS) clots. Histological and immunohistochemical analyses can be applied to extracted AIS thrombi to highlight percentage composition of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) as part of collaborative studies across European stroke centres. MMPs are markers of extracellular matrix degradation, with considerable involvement in the integrity of the blood-brain barrier (BBB) (4). Elevated levels of MMP-2 and MMP-9 are associated with vascular impairment and disturbance of the BBB, suggesting their role in early detection of AIS and post-thrombectomy intracranial haemorrhaging (PTIH) (5).
This project will investigate MMP-2 and MMP-9 levels in AIS clots in regard to aetiology and patient outcomes ie. the National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and modified Treatment In Cerebral Infarction (mTICI). Identifying correlations between thrombus composition, stroke aetiology, and clinical outcomes may help guide strategies to reduce neurological deficits, predict and manage post-thrombectomy intracranial haemorrhaging and optimise recovery time and quality of life for AIS patients.