Treatments in Ischemic Stroke: Current and Future

Abstract

<b><i>Background and Aim:</i></b> Despite progress made over the last 30 years, stroke is still a leading cause of disability and mortality; likewise, its burden is expected to increase over the next decades, due to population growth and aging. The development of drugs with better safety-efficacy profiles as well as strategies able to improve ischemic stroke management from the pre-hospital setting is needed. <b><i>Summary:</i></b> The pathophysiology of ischemic stroke involves multiple pathways resulting in cerebral artery obstruction and brain tissue ischemia. To date, the only approved drug for acute ischemic stroke is intravenous thrombolytic alteplase. Intravenous thrombolysis (IVT) can be administered alone or in combination with endovascular treatment (EVT) with mechanical thrombectomy, in case of large vessel occlusion and generally within 6 h from symptoms onset. The risk of potential bleeding complications, especially symptomatic intracerebral hemorrhage, is one of the reasons for the reluctance to administer IVT. Tenecteplase is a promising alternative fibrinolytic agent, having a better safety profile than alteplase. Moreover, recent evidences have allowed an extension of the IVT ± EVT time window for patients with unknown onset time and for those with a known onset time thanks to the new “tissue-window” approach guided by advanced neuroimaging techniques, which also helps in collateral circulation estimation. Regarding primary-secondary prevention, researchers are focused on improving the efficacy of antithrombotic drugs with a “hemostasis-sparing” approach. Neuroprotective agents are also under development, particularly stem cells. The COVID-19 pandemic has critically stressed global healthcare systems, with collateral damage resulting in access delivery of only emergency care, such as ischemic stroke. Regarding telemedicine, it has had a minor role in acute stroke management, and with the onset of COVID-19, this role will most likely be adopted to increase access and delivery in stroke assessment, but also in the follow-up.

Perspective Chapter: Clinical Standard of a Geriatric Patient as a Virtual Target for Correction of Pharmacotherapy of Hypertension and Stroke in the Elderly

“…In particular, rehabilitation of elderly people after a stroke is often carried out against the background of geriatric syndromes of neuropsychiatric nature and diseases of various organs and systems of somatic nature. Moreover, aging of elderly patients reduces their reactivity, disease resistance, sensitivity to drugs, and the ability to inactivate the administered drugs [39,40].…”

Research progress on the protective mechanism of a novel soluble epoxide hydrolase inhibitor TPPU on ischemic stroke

“…. TPPU inhibits inflammatory response after stroke Inflammation can not only cause a cerebral infarction, but it can also further activate the inflammatory response, creating a vicious circle (15)(16)(17)(18). Tu et al developed a mouse model of cerebral infarction and found that TPPU could significantly promote the recovery of neurological function and reduce the infarct volume and the expression of inflammatory cytokines IL-1βmRNA and TNF-αmRNA, revealing that TPPU may reduce the inflammatory response after infarction and promote the recovery of neurological function (19).…”

Synthesis of Novel 3‐Butylphthalide Derivatives Containing Isopentenylphenol Moiety as Potential Antiplatelet Agents for the Treatment of Ischemic Stroke

“…After concentration, the residue was purified by flash column chromatography on silica gel to give the compound 1 (2.5 g, 62.9 %) as a colorless oil liquid. (2). Compound 1 (2.4 g, 8.8 mmol), Lindlar catalyst (40%, 958.8 mg) under hydrogen atmosphere were dissolved in hexane (50 mL) and stirred for 24 h at 50°C.…”

“…Many experimental and clinical studies have shown that platelet aggregation mediated thrombosis was the main cause of ischemic stroke, which could lead to irreversible ischemic and hypoxic necrosis of brain tissue. Therefore, antithrombotic is well recognized to be the preferred strategy for the treatment of ischemic stroke [2,3] . Currently, the clinically used antithrombotic drugs can be divided into anticoagulants, thrombolytics and antiplatelet aggregation drugs according to the mechanisms of action, but all of them existed a certain degree of defects and side effects in their application, such as narrow therapeutic window, high bleeding risk, increased drug resistance, etc [4] .…”

“…Therefore, antithrombotic is well recognized to be the preferred strategy for the treatment of ischemic stroke. [2,3] Currently, the clinically used antithrombotic drugs can be divided into anticoagulants, thrombolytics and antiplatelet aggregation drugs according to the mechanisms of action, but all of them existed a certain degree of defects and side effects in their application, such as narrow therapeutic window, high bleeding risk, increased drug resistance, etc. [4] Thus, there is an urgent need to explore novel antithrombotic drugs with less side effects and better efficacy to protect patients from ischemic injuries.…”