Update in the Early Management and Reperfusion Strategies of Patients with Acute Ischemic Stroke

Abstract

Acute ischemic stroke (AIS) remains a leading cause of death and long-term disability. The paradigms on prehospital care, reperfusion therapies, and postreperfusion management of patients with AIS continue to evolve. After the publication of pivotal clinical trials, endovascular thrombectomy has become part of the standard of care in selected cases of AIS since 2015. New stroke guidelines have been recently published, and the time window for mechanical thrombectomy has now been extended up to 24 hours. This review aims to provide a focused up-to-date review for the early management of adult patients with AIS and introduce the new upcoming areas of ongoing research.

Blood-Brain Barrier Damage in Ischemic Stroke and Its Regulation by Endothelial Mechanotransduction

“…While studies have demonstrated that alteplase does reduce tissue infarct volume, it does not alter other associated pathophysiologies such as ischemic brain edema (Broocks et al, 2020). While r-tPA has been demonstrated as an efficient and cost-effective thrombolytic agent, its short therapeutic time window of up to 4.5 h, association with severe deleterious events, especially hemorrhagic transformation and brain injury, and candidates' eligibility for treatment (e.g., delayed identification in the emergency department; Sung et al, 2013) greatly limit the safety and application of r-tPA (Mendez et al, 2018). Regarding deleterious events associated with tPA, it has been proposed that tPA exacerbates neuron death in the hippocampus due to inter-neuronal laminin degradation and pro-survival cell-matrix signaling disruption (Lo et al, 2004).…”

Integrin α5β1 inhibition by ATN-161 reduces neuroinflammation and is neuroprotective in ischemic stroke

“…Acute treatment for ischemic stroke is currently limited to recanalization/reperfusion strategies only provided to a minority of patients: intravenous tissue plasminogen activator and/or endovascular thrombectomy. 1–4 While these treatments remove the blood vessel-obstructing thrombus, they fail to impact secondary reperfusion injury. Reperfusion injury results from an influx of factors, including calcium, cytokines, reactive oxygen species, growth factors, and matrix metalloproteinases (MMPs), that induce extracellular matrix (ECM) degradation, leukocyte infiltration, and apoptotic cascades.…”

Neuronal Transmembrane Chloride Transport Has a Time-Dependent Influence on Survival of Hippocampal Cultures to Oxygen-Glucose Deprivation

“…Clinical practice reveals a preclinical setting, during which cerebral ischemia continues, and for which there is currently no approved treatment, as well as a clinical therapeutic window during which revascularization may be attempted. Present guidelines recommend pharmacological or interventional revascularization strategies, which are limited by a time window and have a non-insignificant degree of treatment failure or complication rate [3][4][5]. During acute treatment, patients often receive pharmacological treatments for sedation (e.g., during transport in the preclinical phase, when undergoing interventional procedures, or during intensive care treatment) or for increased intracranial pressure (e.g., after a malignant stroke or intracerebral hemorrhage), which involve modulation of gamma-aminobutyric acid A (GABA A ) receptors or chloride transporters [6][7][8].…”