Caspase-1: A Promising Target for Preserving Blood–Brain Barrier Integrity in Acute Stroke

Ye, Xiaodong; Song, Guini; Huang, Shanshan; Liang, Qiming; Fang, Yongkang; Lian, Lifei; Zhu, Suiqiang

doi:10.3389/fnmol.2022.856372

Cited by 18 publications

(6 citation statements)

References 188 publications

(262 reference statements)

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“…Caspase-1 is an initiator of inflammation or programmed cell death in the CNS [ 17 , 18 ]. Increased caspase-1 expression is associated with various neurodegenerative diseases and BBB dysfunction [ 19 ]. Therefore, caspase-1 is a possible target for neurodegenerative diseases or BBB restoration [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

The Preventive Effect of Urinary Trypsin Inhibitor on Postoperative Cognitive Dysfunction, on the Aspect of Behavior, Evaluated by Y-Maze Test, via Modulation of Microglial Activity

Cho,

In,

Lee

et al. 2024

IJMS

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This experimental study was designed to evaluate the effect of ulinastatin, a urinary trypsin inhibitor, on postoperative cognitive dysfunction (POCD) in rats under general anesthesia with isoflurane, on the aspect of behavior, as evaluated using a Y-maze test and focusing on microglial activity. Ulinastatin (50,000 U/mL) and normal saline (1 mL) were randomly (1:1) administered intraperitoneally to the ulinastatin and control groups, respectively, before general anesthesia. Anesthesia with isoflurane 1.5 volume% was maintained for 2 h. The Y-maze test was used to evaluate cognitive function. Neuronal damage using caspase-1 expression, the degree of inflammation through cytokine detection, and microglial activation with differentiation of the phenotypic expression were evaluated. Twelve rats were enrolled in the study and evenly allocated into the two groups, with no dropouts from the study. The Y-maze test showed similar results in the two groups before general anesthesia (63 ± 12% in the control group vs. 64 ± 12% in the ulinastatin group, p = 0.81). However, a significant difference was observed between the two groups after general anesthesia (17 ± 24% in the control group vs. 60 ± 12% in the ulinastatin group, p = 0.006). The ulinastatin group showed significantly lower expression of caspase-1. Pro-inflammatory cytokine levels were significantly lower in the ulinastatin group than in the control group. The ulinastatin group had a significantly lower microglial activation (41.74 ± 10.56% in the control group vs. 4.77 ± 0.56% in the ulinastatin, p < 0.001), with a significantly lower activation of M1 phenotypes (52.19 ± 7.83% in the control group vs. 5.58 ± 0.76% in the ulinastatin group, p < 0.001). Administering ulinastatin before general anesthesia prevented neuronal damage and cognitive decline after general anesthesia, in terms of the aspect of behavior, as evaluated by the Y-maze test. The protective effect of ulinastatin was associated with the inhibition of microglial activation, especially the M1 phenotype.

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Section: Discussionmentioning

confidence: 99%

The Preventive Effect of Urinary Trypsin Inhibitor on Postoperative Cognitive Dysfunction, on the Aspect of Behavior, Evaluated by Y-Maze Test, via Modulation of Microglial Activity

Cho,

In,

Lee

et al. 2024

IJMS

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“…Caspase-1 is situated in the cytosol as inactive form procaspase-1 after translation. Procaspase-1 has a total of 3 domains (CARD, p20, p10), which transformed into caspase-1 after inflammasomes activation [42] . After the assembly and triggering of inflammasomes, caspase-1 mediated pyroptosis ensues with release of GSDMD and mature of inflammatory cytokines (IL-1β and IL-18).…”

Section: Discussionmentioning

confidence: 99%

Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation

Ga,

Wei,

Zhao

et al. 2024

Food Science and Human Wellness

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Ulcerative colitis (UC) is a common infl ammatory disease of the gastrointestinal tract. Traditional Chinese medicine (TCM) has long been used in Asia as a treatment for UC and Puerariae Radix (PR) is a reliable anti-diarrheal therapy. The aims of this study were to investigate the protective effect of PR using the dextran sulfate sodium salt (DSS)-induced UC model in mice and identify molecular mechanisms of PR action. The chemical constituents of PR via ultra-performance liquid chromatography/tandem mass spectrometry and identifi ed potential PR and UC targets using a network pharmacology (NP) approach were obtained to guide mouse experiments. A total of 180 peaks were identifi ed from PR including 48 fl avonoids, 46 organic acids, 14 amino acids, 8 phenols, 8 carbohydrates, 7 alkaloids, 6 coumarins and 43 other constituents. NP results showed that caspase-1 was the most dysregulated of the core genes associated with UC. A PR dose of 0.136 mg/g administered to DSS treated mice reversed weight loss and decreased colon lengths found in UC mice. PR also alleviated intestinal mucosal shedding, infl ammatory cell infi ltration and mucin loss. PR treatment suppressed upregulation of NOD-like receptor protein 3 (NLRP3), cysteinyl aspartate-specific proteases-1 (caspase-1), apoptosis-associated speck-like (ASC) and gasdermin D (GSDMD) at both the protein and mRNA expression levels. The addition of a small molecule dual-specifi city phosphatase inhibitor NSC 95397 inhibited the positive effects of PR. These results indicated that PR exerts a protective effect on DSS-induced colitis by inhibiting NLRP3 infl ammasome activation in mice.

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“…This is a form of programmed cell death that is implicated in neuronal death during IS. Pyroptosis is mediated by the activation of caspase-1, triggered by the formation of inflammasomes in response to cerebral ischemia [ 42 ]. Inflammasomes are multi-protein complexes that consist of sensor proteins NLRP1, NLRP3, and NLRP4 that play a role in processing pro-inflammatory cytokines [ 43 ].…”

Section: Etiology and Pathophysiology Of Ischemic Strokementioning

confidence: 99%

Understanding the Pathophysiology of Ischemic Stroke: The Basis of Current Therapies and Opportunity for New Ones

Salaudeen,

Bello,

Danraka

et al. 2024

Biomolecules

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The majority of approved therapies for many diseases are developed to target their underlying pathophysiology. Understanding disease pathophysiology has thus proven vital to the successful development of clinically useful medications. Stroke is generally accepted as the leading cause of adult disability globally and ischemic stroke accounts for the most common form of the two main stroke types. Despite its health and socioeconomic burden, there is still minimal availability of effective pharmacological therapies for its treatment. In this review, we take an in-depth look at the etiology and pathophysiology of ischemic stroke, including molecular and cellular changes. This is followed by a highlight of drugs, cellular therapies, and complementary medicines that are approved or undergoing clinical trials for the treatment and management of ischemic stroke. We also identify unexplored potential targets in stroke pathogenesis that can be exploited to increase the pool of effective anti-stroke and neuroprotective agents through de novo drug development and drug repurposing.

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Caspase-1: A Promising Target for Preserving Blood–Brain Barrier Integrity in Acute Stroke

Cited by 18 publications

References 188 publications

The Preventive Effect of Urinary Trypsin Inhibitor on Postoperative Cognitive Dysfunction, on the Aspect of Behavior, Evaluated by Y-Maze Test, via Modulation of Microglial Activity

The Preventive Effect of Urinary Trypsin Inhibitor on Postoperative Cognitive Dysfunction, on the Aspect of Behavior, Evaluated by Y-Maze Test, via Modulation of Microglial Activity

Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation

Understanding the Pathophysiology of Ischemic Stroke: The Basis of Current Therapies and Opportunity for New Ones

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