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.
Highlights
According to the World Health Organization (WHO), each year, 15 million people suffer a stroke worldwide, of whom five million die and another five million show chronic disability [1,2]
In some other clinical trials, recanalization has been evaluated according to the Thrombolysis in Myocardial Ischemia (TIMI) grading scale or the Thrombolysis in Brain Ischemia (TIBI), but using these scores does not provide any details about different partial patterns of recanalization
The increase of hemorrhagic transformation (HT) with recombinant tissue plasminogen activator (rt-PA) is not always clinically relevant, and it is still a matter of debate as to how rt-PA could enhance the extent of HT, and at the same time improve patients’ functional outcomes [109,110]. Clinical data from both European Cooperative Acute Stroke Studies (ECASS) 1 and 2 indicate that, rt-PA increases the risk of HT, it reduces the overall risk for disability and death by 6% and 8%, respectively [111,112]
Summary
According to the World Health Organization (WHO), each year, 15 million people suffer a stroke worldwide, of whom five million die and another five million show chronic disability [1,2]. Clinicians are confronted with several obstacles when attempting recanalization therapy for stroke patients: (1) recanalization fails, (2) absence of reperfusion “no-reflow” or “reocclusion”, and (3) vascular complications such as hemorrhagic transformation (HT). These problems have been understudied, but with increasing use of thrombectomy in stroke, the need to understand the vascular and cerebral blood flow (CBF) changes associated with recanalization cannot be overemphasized. Each of these problems in reinstalling normal perfusion after stroke can be approached from the molecular level, since several genes and proteins are induced after stroke and/or recanalization (Figure 1)
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