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Ischemic stroke is an acute cerebrovascular disease with a high morbidity, mortality, and disability rate. Persistent ischemia of brain tissue can cause irreversible damage to neurons, leading to neurological dysfunction and seriously affecting patients' quality of life. However, current clinical therapies are limited and have not achieved satisfactory outcome, due to the incomplete understanding of the mechanism of neuronal damage during ischemic stroke. Recent studies have found that ferroptosis is implicated in the pathophysiology of ischemic stroke. Ferroptosis is an iron-dependent regulated cell death driven by lipid peroxidation. Under normal physiological conditions, GSH/GPX4, FSP1/CoQ 10 , GCH/BH 4 and other anti-ferroptosis pathways can function effectively to suppress the occurrence of ferroptosis. After ischemic stroke, two typical ferroptosis characteristics, lipid peroxidation and iron accumulation, are observed, accompanied by changes in the expression of ferroptosis related genes such as GPX4, ACSL4, and SLC7A11, suggesting that ferroptosis plays a key role in ischemic stroke, which provides a new idea for the clinical treatment of ischemic stroke. This article reviewed the pathological mechanisms of ferroptosis in the occurrence and development of ischemic stroke, as well as the related progress of ferroptosis targeted therapy., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Ischemic stroke is a worldwide disease that seriously threatens human health, and there are few effective drugs to treat it. Dihydromyricetin (DHM) has anti-inflammatory, antioxidant, and antiapoptotic functions. We identified pyroptosis following ischemic stroke. Here, we investigated the effect of DHM on ischemic stroke and pyroptosis. In the first part of the experiment, Sprague-Dawley rats were randomly divided into the sham group and MCAO group. The MCAO model was established by occlusion of the middle cerebral artery for 90 min using a silica gel suture. The ischemic penumbra was used for mRNA sequencing 1 day after reperfusion. In the second part, rats were divided into the sham group, MCAO group, and DHM group. DHM was injected intraperitoneally at the same time as reperfusion starting 90 min after embolization for 7 consecutive days. The changes in pyroptosis were observed by morphological and molecular methods. The transcriptomics results suggested the presence of NLRP3-mediated pyroptotic death pathway activation after modeling. The Longa score was increased after MCAO and decreased after DHM treatment. 2,3,5-Triphenyltetrazolium chloride (TTC) staining showed that DHM could reduce the infarct volume induced by MCAO. Nissl staining showed disordered neuronal arrangement and few Nissl bodies in the MCAO group, but this effect was reversed by DHM treatment. Analysis of pyroptosis-related molecules showed that the MCAO group had serious pyroptosis, and DHM effectively reduced pyroptosis. Our results demonstrate that DHM has a neuroprotective effect on ischemic stroke that is at least partly achieved by reducing pyroptosis., (© 2023. The American Society for Experimental Neurotherapeutics, Inc.)

Ischemic stroke (IS) is an acute brain injury and a major cause of disability and mortality worldwide, resulting from permanent or temporary cerebral artery occlusion. Thrombolysis and antithrombotic therapy or thrombectomy over a wider therapeutic window led to reduced stroke mortality. However, the post-stroke pathological mechanism is still elusive, involving sustaining inflammation and cellular dysfunction, which hinders the recovery after IS. Thus, more attention is shifting towards the complex interactions of the neurovascular unit (NVU) and its important role in the progress of inflammation recently. This review summarized the physiological function of each component of the NVU and their functions on blood brain barrier permeability, cerebral blood flow regulation and the inflammation progress after IS. In addition, we described the inflammation-related pathological changes affected by the NVU and concluded that the dysfunction of the NVU contributed to the inflammation progress after IS. This review may provide ideas for the potential therapies targeting the NVU for improving the prognosis of IS., Competing Interests: Conflict of interest disclosure The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Stroke is the main cause of death in Chinese residents, bringing a heavy economic burden to patients. This study aims to explore the characteristics and the factors influencing the hospitalization cost for stroke, and to provide scientific evidence for reducing the economic burden on stroke patients., Methods: The data were mainly obtained from the Shanghai Statistics Center for Health. Using the coding system of International Classification of Diseases (ICD)-10, we retrospectively collected the stroke-related first hospitalization records of stroke patients in J district, Shanghai during January 1, 2016 to December 31, 2019 whose main diagnostic disease codes were I61-I63. After cleaning and arranging the data, we counted the first hospitalization cost and length of hospital stay (LOS) of the patients. Univariate analysis was performed using non-parametric tests, and the factors influencing stroke hospitalization cost were further analyzed by multiple linear regression fitting path model., Results: A total of 3 901 stroke patients were included. Ischemic and hemorrhagic stroke patients accounted for 92.59% and 7.41%, respectively, of which the mean hospitalization cost per patient were 12 397.35 yuan and 28 814.72 yuan, respectively, and the mean LOS per patient were 13 days and 19 days, respectively. Hospitalization cost for ischemic stroke mainly consisted of medicine fees, diagnosis fees, and service fees, accounting for 44.70%, 29.92%, and 15.42%, respectively, and hospitalization cost for hemorrhagic stroke mainly consisted of medicine fees, diagnosis fees, consumables fees, and service fees, accounting for 38.76%, 18.33%, 17.59%, and 15.38%, respectively. From 2016 to 2019, the proportion of medicine fees for ischemic stroke was decreased by 19.38 percentage points, and the diagnosis fees and service fees were increased by 8.43 percentage points and 9.04 percentage points, respectively; the proportions of medicine fees and consumables fees for hemorrhagic stroke were decreased by 7.54 percentage points and 13.43 percentage points, respectively, and the proportions of diagnostic fees and service fees were increased by 6.87 percentage points and 10.15 percentage points, respectively. Path analysis results showed that the main direct factors influencing hospitalization cost were the LOS, hospital level, operation, and year, and the main indirect factors were age and hospital level (all P <0.05)., Conclusions: The cost burden of stroke patients in Shanghai is relatively heavy, and we should continue to promote the medical reform policy and consolidate the achievements of medical reform. Hospitals should strengthen clinical pathway management and patient health education to improve medical efficiency and reduce invalid hospitalization days. Government departments should continue to improve the medical insurance system, enhance the supervision to medical insurance, and promote health equity.

The inflammatory and immune processes are key pathophysiological processes in the ischemic stroke, including leukocyte infiltration and destruction of the blood-brain-barrier (BBB), which further lead to increased post-ischemic inflammation. Regulatory T cells (Tregs) are a specific subset of T lymphocytes that play a pivotal role in suppressing the activation of immune system, maintaining immune homeostasis, and regulating inflammation induced by pathogens and environmental toxins. We would like to discuss the paradox function of Tregs in ischemic stroke. The accumulating data indicate that Tregs are involved in the immune regulation and self-tolerance after ischemic stroke, contributing the outcome of ischemic stroke. Tregs could resist immune response overactivation, and were supposed to be the endogenous regulatory factors to control the immune response of ischemic brain. Although, there are still some controversies and unresolved issues about the functions and mechanisms of Tregs in ischemic stroke. More and more attention has been paid to Tregs in the pathogenesis of ischemic stroke and it might be a potential therapeutic target in the future. In this review, we will summarize the recent findings on the specific functions and mechanisms of Tregs and discuss its potential therapeutic role in ischemic stroke., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Salvinorin A (SA) exerts neuroprotection and improves neurological outcomes in ischemic stroke models in rodents. In this study, we investigated whether intranasal SA administration could improve neurological outcomes in a monkey ischemic stroke model. The stroke model was induced in adult male rhesus monkeys by occluding the middle cerebral artery M2 segment with an autologous blood clot. Eight adult rhesus monkeys were randomly administered SA or 10% dimethyl sulfoxide as control 20 min after ischemia. Magnetic resonance imaging was used to confirm the ischemia and extent of injury. Neurological function was evaluated using the Non-Human Primate Stroke Scale (NHPSS) over a 28-day observation period. SA significantly reduced infarct volume (3.9 ± 0.7 cm 3 vs. 7.2 ± 1.0 cm 3 ; P  =   0.002), occupying effect (0.3 ± 0.2% vs. 1.4 ± 0.3%; P  =   0.002), and diffusion limitation in the lesion (-28.2 ± 11.0% vs. -51.5 ± 7.1%; P  =   0.012) when compared to the control group. SA significantly reduced the NHPSS scores to almost normal in a 28-day observation period as compared to the control group ( P  =   0.005). Intranasal SA reduces infarct volume and improves neurological outcomes in a rhesus monkey ischemic stroke model using autologous blood clot.

Methylene blue, the FDA-grandfathered drug was proved to be neuroprotective in ischemic stroke in rat. However, the mechanism of the protective effect was unknown. In this study, we used different animal models to investigate the effect of MB administration given within and beyond the therapeutic time window on behavioral deficits and infarct volume and related mechanism about the white matter protection. Middle cerebral artery occlusion and reperfusion (MCAO) and photothrombotic middle cerebral artery occlusion (PT-MCAO) models were used. Behavioral deficits and infarct volume were measured by foot fault test, Garcia neurological score, and TTC staining. Black gold staining and western blot were used to evaluate the brain white matter injury. We found that intraperitoneal administration of MB immediately or 24 h after the MCAO or PT-MCAO surgery reduced infarct volume, improved the neurological deficits, and reduced the white matter injury via myelin basic protein (BMP) protection. These findings suggested that MB relieved the white matter injury besides neuronal protection and has potential therapeutic effects on ischemic stroke., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Quancheng Cheng et al.)

Autophagy is a strictly regulated process that degrades and recycles long-lived or misfolded proteins and damaged organelles for the maintenance of energy and function homeostasis of cells. Insufficient oxygen and glucose supply caused by cerebral ischemia lead to a higher ratio of AMP/ATP, which will activate the AMPK pathway to initiate the process of autophagy. Accumulating evidence shows that autophagy participates in the pathogenesis of ischemic stroke as a double- edged sword. However, the exact role of autophagy in the pathogenesis of ischemic stroke is controversial and yet to be elucidated. In this review, the autophagy pathway, both in physiological conditions and in ischemic stroke, is expounded. The focus was also on discussing the doubleedged sword effect of autophagy in brain ischemia and its underlying mechanisms. In addition, potential therapeutic strategies for ischemic stroke targeting autophagy pathway were also reviewed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)