Clot Fragments Formed from Original Thrombus Obstruct Downstream Arteries in the Ischemic Injured Brain

Abstract

The present study thus reveals the mechanisms of the downstream arterial occlusion following the dissolution of original thrombus.

Microembolus clearance through angiophagy is an auxiliary mechanism preserving tissue perfusion in the rat brain

“…Furthermore, the introduction of intra-arterial thrombectomy in the treatment of acute ischemic stroke has surfaced a major challenge in the field. Recanalization of the occluded artery is achieved in the large majority of patients after thrombectomy, yet the procedure itself may result in emboli showers dislodging from the main thrombus [4,5,29], causing widespread microvascular perfusion deficits distal of the initial event [29].…”

“…Although the three-dimensional microvasculature is highly interconnected, collateral microvascular flow is not always sufficient to maintain tissue perfusion. Whereas the brain has endogenous fibrinolytic capacity [25,29], many emboli are poorly susceptible to this enzymatic degradation [17], with prolonged vessel occlusion and hypoxia as a result. Notably, the endothelium has the potential to engulf microparticles from the circulation and extrude them on the abluminal side, in a process called angiophagy.…”

A Concept of Thrombolysis as a Corrosion–Erosion Process Verified by Optical Microscopy

“…An interesting alternative to the study of thrombolysis by analysis of fibrin degradation products on the molecular scale using biochemical methods is the analysis of the clot surface on the cell scale using optical microscopy. Clot fragmentation was evidenced by optical microscopy in ex vivo study of animal model clot dissolution in cerebral arteries [27]. As blood clots are made of blood cells interconnected by the fibrin network, which during thrombolysis degrades to clot fragments of various sizes, optical microscopy proved very efficient for studying effects of flow on the course of thrombolysis [1].…”

Animal Models of Focal Cerebral Ischaemia and Haemorrhagic Transformation: Considerations in Experimental Stroke Study Design

“…The thromboembolic model provides useful information on the behaviour of clots in situ, such as providing evidence for spontaneous breakdown and subsequent distal microthrombi formation [78], and studying therapeutic interventions based on targeting the clot.…”

“…The variation in this model has been reduced by modifying the clot characteristics, notably length, diameter and use of fibrin-rich clots, in order to better model the clinical situation [76]. In addition, there is the risk of spontaneous recanalisation due to the breakdown of the clot in situ during the occlusion period [78] which can increase infarct variation. As such, it is considered that this model is not suitable for testing and/or validating neuroprotective interventions.…”