Improving Cerebral Blood Flow after Arterial Recanalization: A Novel Therapeutic Strategy in Stroke

Mohamad El Amki, Susanne Wegener, Mohamad El Amki, Susanne Wegener

Abstract

Ischemic stroke is caused by a disruption in blood supply to a region of the brain. It induces dysfunction of brain cells and networks, resulting in sudden neurological deficits. The cause of stroke is vascular, but the consequences are neurological. Decades of research have focused on finding new strategies to reduce the neural damage after cerebral ischemia. However, despite the incredibly huge investment, all strategies targeting neuroprotection have failed to demonstrate clinical efficacy. Today, treatment for stroke consists of dealing with the cause, attempting to remove the occluding blood clot and recanalize the vessel. However, clinical evidence suggests that the beneficial effect of post-stroke recanalization may be hampered by the occurrence of microvascular reperfusion failure. In short: recanalization is not synonymous with reperfusion. Today, clinicians are confronted with several challenges in acute stroke therapy, even after successful recanalization: (1) induce reperfusion, (2) avoid hemorrhagic transformation (HT), and (3) avoid early or late vascular reocclusion. All these parameters impact the restoration of cerebral blood flow after stroke. Recent advances in understanding the molecular consequences of recanalization and reperfusion may lead to innovative therapeutic strategies for improving reperfusion after stroke. In this review, we will highlight the importance of restoring normal cerebral blood flow after stroke and outline molecular mechanisms involved in blood flow regulation.

Keywords: collaterals; hemorrhagic transformation; no-reflow and reocclusion; reperfusion; stroke.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Vascular challenges for reperfusion therapy. (a) Schematic diagram of a coronal section of the brain. The middle cerebral artery (MCA) is occluded with a blood clot. The blue areas correspond to the infarct that could be saved with reperfusion therapy (b). The different possible pitfalls of reperfusion are shown as no recanalization (c), recanalization but no reperfusion and arterial reocclusion and no-reflow (d), and vascular complications: hemorrhagic transformation (e). In c–e, a summary of potential molecules involved in blood flow regulation is given for each scenario. Abbreviations: GPIIb/IIIa, glycoprotein IIb/IIIa receptors; VEGF, Vascular Endothelial Growth Factor; TAFI, Thrombin Activatable Fibrinolysis Inhibitor; PAI-1, Plasminogen Activator Inhibitor-1; ICAM-1, Intercellular Adhesion Molecule 1; MMP, Matrix Metalloproteinases; PARP, Poly-ADP-Ribose Polymerase.
Figure 2
Figure 2
Impact of collateral flow on clot lysis and reperfusion. (a) Schematic drawing of the collateral network showing anastomoses between the middle cerebral artery (MCA) and anterior cerebral artery (ACA); (b) in stroke with a poor collateral network, the collaterals fail to fill and insufficiently compensate the flow reduction after arterial occlusion; (c) a collateral enhancement occurring in patients showing good collateral network. The flow in the collaterals changes direction and allows the thrombolytic to reach the drug from different sides.

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