The evaluation and characterisation of thrombin-induced mammalian thrombi models for the investigation of vascular occlusion in acute ischemic stroke.

A lack of blood supply to any part of the brain for an unknown period of time may lead to brain tissue necrosis, commonly known as stroke. Stroke remains the third most common cause of death worldwide and kills more than 2,000 people a year in Ireland. This is a higher death toll than those who die from breast cancer, prostate cancer and bowel cancer combined. Stroke is also the leading cause of acquired long-term disability and is almost twice as prevalent among women as men. Over 80% of all strokes are ischaemic that can result from a thrombus occlusion of a major cerebral artery.

Thrombosis is an important repair mechanism within the human body but also occurs if blood flow becomes stagnant. In vivo, erythrocyte rich thrombi are generally formed in relatively static, low flow-regions, as with arterial fibrillation. Animal thrombi models have played a unique role in understanding the pathophysiology, morphology and mechanical characteristics of thrombi underlying the vascular occlusion in acute ischemic stroke.

This project concerns the histological and mechanical examination and characterisation of thrombin induced, erythrocyte rich mammalian thrombi. Haemotoxylin and Eosin stains were completed on ovine and bovine thrombi specimens at day 1 and day 33(n=35). The presence of nuclei and erythrocytes correlated significantly with stained human thrombi samples reported from literature. Compositional differences were noticed in the thrombi after 33 days. Tensile and compression tests were conducted at varying strain rates. Initial results indicate a possible increase in elasticity with increase in thrombin concentration (NIH units/ml blood). There was also a decrease in stiffness of 33-day old thrombi compared to 1-day old thrombi.

The successful development of such thrombus models may provide a basis for the characterisation of post-operative thrombi removed from humans. Knowledge about the histological characteristics of thrombi may provide a means for improving current endovascular therapies and the development of new treatment strategies for revascularisation in patients with acute ischemic stroke. These findings could indicate that the composition of thrombi is a potential key variable regarding the selection of the appropriate treatment options for ischemic stroke patients and in predicting the performance of mechanical thrombectomy devices and thrombolytics.