Emerging neuroprotective strategies for the treatment of ischemic stroke: An overview of clinical and preclinical studies

Paul, Surojit; Candelario‐Jalil, Eduardo

doi:10.1016/j.expneurol.2020.113518

Cited by 351 publications

(158 citation statements)

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“…Stroke is the second leading cause of mortality worldwide, with an annual mortality of ~5.5 million, and causes disability in 50% of survivors (1). Ischemic stroke accounts for 75-85% of all strokes and is a pathological state characterized by limited blood flow (2).…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine attenuates neuronal injury induced by cerebral ischemia‑reperfusion by regulating miR‑199a

Zhu

Zhao

Zhang³

et al. 2021

Mol Med Rep

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As is well known, dexmedetomidine (DEX) serves a neuroprotective role in cerebral ischemia-reperfusion (CIR) injury, and microRNA (miR)-199a has been re-ported to be associated with IR injury. However, the association between DEX and miR-199a in CIR injury remains unknown. Thus, the aim of the present study was to verify whether the neuroprotective effect of DEX on cerebral ischemia-reperfusion rats is associated with miR-199a. A rat model of CIR was established, and the modified neurological severity score (mNSS) was evaluated. The effect of DEX on the patholog-ical structure of the cerebral cortex in CIR rats was observed by hematoxylin and eosin and Nissl staining. Reverse transcription-quantitative PCR was used to analyze the expression levels of miR-199a in brain tissue following intracerebroventricular injection of miR-199a antagomir. The co-expression of NeuN and microtubule-associated proteins 1A/1B light chain 3B in the cerebral cortex was analyzed by immunofluorescence staining. Western blotting and immunohistochemistry were performed to analyze the expression of autophagy-associated proteins in the brain tissue. DEX inhibited the expression of miR-199a, decreased the mNSS and improved pathological damage to the cerebral cortex. DEX also inhibited autophagy and expression levels of associated proteins and decreased nerve cell injury. In conclusion, DEX inhibited expression of miR-199a and improved neurocyte injury induced by CIR.

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Section: Introductionmentioning

confidence: 99%

Dexmedetomidine attenuates neuronal injury induced by cerebral ischemia‑reperfusion by regulating miR‑199a

Zhu

Zhao

Zhang³

et al. 2021

Mol Med Rep

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“…The latest safety and efficacy of intravenous glyburide on brain swelling after a large hemispheric infarction (GAMES-RP) clinical trial established a massive attenuation in cerebral edema and midline movement without an effect on the results [ 58 ]. The industry-sponsored Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous BIIB093 (Glibenclamide) for Severe Cerebral Edema Following Large Hemispheric Infarction (CHARM) clinical trial examining a comparable hypothesis involving the sulfonylurea glibenclamide is afoot (ClinicalTrials.gov: NCT0286495) [ 59 , 60 ]. Subsequent to hemorrhagic stroke engendering tissue injury, NLRP3 inflammasome stimulation has been chronicled [ 61 ].…”

Section: Inhibitors Of Nlrp3 Inflammasome-driven In Vivo Disease Modelsmentioning

confidence: 99%

Promise of the NLRP3 Inflammasome Inhibitors in In Vivo Disease Models

et al. 2021

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Nucleotide-binding oligomerization domain NOD-like receptors (NLRs) are conserved cytosolic pattern recognition receptors (PRRs) that track the intracellular milieu for the existence of infection, disease-causing microbes, as well as metabolic distresses. The NLRP3 inflammasome agglomerates are consequent to sensing a wide spectrum of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). Certain members of the NLR family have been documented to lump into multimolecular conglomerates called inflammasomes, which are inherently linked to stimulation of the cysteine protease caspase-1. Following activation, caspase-1 severs the proinflammatory cytokines interleukin (IL)-1β and IL-18 to their biologically active forms, with consequent commencement of caspase-1-associated pyroptosis. This type of cell death by pyroptosis epitomizes a leading pathway of inflammation. Accumulating scientific documentation has recorded overstimulation of NLRP3 (NOD-like receptor protein 3) inflammasome involvement in a wide array of inflammatory conditions. IL-1β is an archetypic inflammatory cytokine implicated in multiple types of inflammatory maladies. Approaches to impede IL-1β’s actions are possible, and their therapeutic effects have been clinically demonstrated; nevertheless, such strategies are associated with certain constraints. For instance, treatments that focus on systemically negating IL-1β (i.e., anakinra, rilonacept, and canakinumab) have been reported to result in an escalated peril of infections. Therefore, given the therapeutic promise of an NLRP3 inhibitor, the concerted escalated venture of the scientific sorority in the advancement of small molecules focusing on direct NLRP3 inflammasome inhibition is quite predictable.

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“…A cost-effectiveness study of IS intervention displayed that IS routine care costs for 13,940 RMB a year [8]. So far, some progresses have been made to assist patients in recovering from IS, with improvement in recanalization therapy using pharmacological and mechanical thrombolysis [9]. At present, drug interventions such as oral thrombolytics and anticoagulants are applied to patients with previous stroke, but some of them respond poorly to these drugs.…”

Section: Introductionmentioning

confidence: 99%

Long-Term Effect of Left Atrial Appendage Occlusion in Treating Patients with Previous Ischemic Stroke on the Disease Recurrence

Yu¹,

Liu²,

Sun³

et al. 2021

Computational and Mathematical Methods in Medicine

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Background and Objective. Thrombolytics and anticoagulants are conventional drugs for ischemic stroke (IS) treatment, whereas some patients have unfavorable responses to these drugs. The disease presents a relatively high recurrence rate. This investigation attempted to unveil the long-term effect of left atrial appendage occlusion (LAAO) in treating patients with previous IS on the disease recurrence. Methods. A total of 120 patients with IS admitted to Tangdu Hospital from July 2016 to September 2017 were grouped into the control group ( n = 60 ) and the observation group ( n = 60 ). Patients in the control group were only treated with thrombolytics and anticoagulants while those in the observation group were treated with both drugs and LAAO. Transesophageal echocardiography (TEE) was performed to observe the occlusion of LAA in patients in the observation group after 45 d and 6 months, respectively. Clinical outcomes in two groups were compared from the following aspects: recurrence of IS, incidence of systemic embolism, and the 3-year recurrence-free survival (RFS). The 3-year IS recurrence of patients was compared by Fisher’s exact test. Results. No significant differences were observed at baseline levels (age, sex, etc.) between the observation group and control group ( p > 0.05 ). During follow-up visit of 45 d and 6 months, all occluders met the efficacious occludsion criteria. The results of TEE at 45 d after LAAO showed that 50% of patients (30/60) in the observation group had complete occlusion of LAA. The results of TEE at 6 months after LAAO suggested that 58.3% of patients (35/60) had complete occlusion of LAA. IS recurrence in the observation group (3.33%, 2/60) was significantly lower than that in the control group (18.33%, 11/60), with the difference presenting statistical significance ( p = 0.008 ). Incidence of systemic embolism in the observation group (1.67%, 1/60) was markedly lower than that in the control group (13.33%, 11/60) ( p = 0.014 ). The average RFS in the observation group (31.97 months, 95% CI: 27.50~32.31 months) was notably longer than that in the control group (29.91 months, 95% CI: 29.85~32.92 months) ( p < 0.05 ). The 3-year IS recurrence of patients between two groups compared by Fisher’s exact test showed significant differences (1 year: p = 0.014 , 2 year: p = 0.008 , 3 year: p = 0.008 ). Conclusion. Regarding patients with previous IS who had poor response to thrombolytics and anticoagulants, LAAO could effectively decrease recurrence of IS and incidence of systemic embolism and prolong RFS of patients. LAAO was, therefore, an alternative for patients with high IS recurrence risk.

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Emerging neuroprotective strategies for the treatment of ischemic stroke: An overview of clinical and preclinical studies

Cited by 351 publications

References 443 publications

Dexmedetomidine attenuates neuronal injury induced by cerebral ischemia‑reperfusion by regulating miR‑199a

Dexmedetomidine attenuates neuronal injury induced by cerebral ischemia‑reperfusion by regulating miR‑199a

Promise of the NLRP3 Inflammasome Inhibitors in In Vivo Disease Models

Long-Term Effect of Left Atrial Appendage Occlusion in Treating Patients with Previous Ischemic Stroke on the Disease Recurrence

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