Selective mGluR1 Negative Allosteric Modulator Reduces Blood–Brain Barrier Permeability and Cerebral Edema After Experimental Subarachnoid Hemorrhage

Zhang, Cheng; Jiang, Ming; Wang, Weiqi; Zhao, Shijun; Yin, Yanxin; Mi, Qiong-Jie; Yang, Mo; Song, Yuqiang; Sun, Bo; Zhang, Zongyong

doi:10.1007/s12975-019-00758-z

Cited by 55 publications

(48 citation statements)

References 44 publications

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“…The treatments identified in this study include both (1) potential novel IBD treatments (Table 1 )[ 10 - 73 ]; and (2) examples of recently studied IBD treatments that would have also been identified as potential novel treatments had this study been performed in 2016 (Table 2 )[ 74 - 95 ]. The latter reflect the predictive nature of the LRDI treatment repurposing technique.…”

Section: Resultsmentioning

confidence: 99%

Treatment repurposing for inflammatory bowel disease using literature-related discovery and innovation

Kostoff

Briggs²,

Shores

2020

WJG

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Inflammatory bowel disease (IBD) incidence has been increasing steadily, most dramatically in the Western developed countries. Treatment often includes lifelong immunosuppressive therapy and surgery. There is a critical need to reduce the burden of IBD and to discover medical therapies with better efficacy and fewer potential side-effects. Repurposing of treatments originally studied in other diseases with similar pathogenesis is less costly and time intensive than de novo drug discovery. This study used a treatment repurposing methodology, the literature-related discovery and innovation (LRDI) text mining system, to identify potential treatments (developed for non-IBD diseases) with sufficient promise for extrapolation to treatment of IBD. By searching for desirable patterns of twenty key biomarkers relevant to IBD ( e.g ., inflammation, reactive oxygen species, autophagy, barrier function), the LRDI-based query retrieved approximately 9500 records from Medline. The most recent 350 records were further analyzed for proof-of-concept. Approximately 18% (64/350) met the criteria for discovery (not previously studied in IBD human or animal models) and relevance for application to IBD treatment. Many of the treatments were compounds derived from herbal remedies, and the majority of treatments were being studied in cancer, diabetes, and central nervous system disease, such as depression and dementia. As further validation of the search strategy, the query identified ten treatments that have just recently begun testing in IBD models in the last three years. Literature-related discovery and innovation text mining contains a unique search strategy with tremendous potential to identify treatments for repurposing. A more comprehensive query with additional key biomarkers would have retrieved many thousands more records, further increasing the yield of IBD treatment repurposing discovery.

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Section: Resultsmentioning

confidence: 99%

Treatment repurposing for inflammatory bowel disease using literature-related discovery and innovation

Kostoff

Briggs²,

Shores

2020

WJG

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“…The BBB is an important system responsible for maintaining the cerebral microenvironment [ 164 ]. The function and structure of BBB would be damaged after stroke, further aggravating the pathological changes.…”

Section: Pacap and Potential Mechanism Of Neuroprotection In Strokementioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide: A Promising Neuroprotective Peptide in Stroke

et al. 2020

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The search for viable, effective treatments for acute stroke continues to be a global priority due to the high mortality and morbidity. Current therapeutic treatments have limited effects, making the search for new treatments imperative. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a well-established cytoprotective neuropeptide that participates in diverse neural physiological and pathological activities, such as neuronal proliferation, differentiation, and migration, as well as neuroprotection. It is considered a promising treatment in numerous neurological diseases. Thus, PACAP bears potential as a new therapeutic strategy for stroke treatment. Herein, we provide an overview pertaining to the current knowledge of PACAP, its receptors, and its potential neuroprotective role in the setting of stroke, as well as various mechanisms of neuroprotection involving ionic homeostasis, excitotoxicity, cell edema, oxidative stress, inflammation, and cell death, as well as the route of PACAP administration.

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“…The miR-125-b-2-3p inhibitor (0.5 nmol/pup, rno-miR-125b-22-3p miRCURY LNA miRNA Power Inhibitor, Qiagen, Cat#YI04109200-DDA), or the anti-miR control (0.5 nmol/pup, miRCURY LNA miRNA Power Inhibitor control, Qiagen, Cat#YI00199006-DDA) was administered to the right lateral ventricle at 24 h before HI. The intracerebroventricular injection was performed as previously described [30,31]. Pups were placed in a stereotactic frame under isoflurane anesthesia.…”

Section: Intracerebroventricular Injectionmentioning

confidence: 99%

IRE1α inhibition attenuates neuronal pyroptosis via miR-125/NLRP1 pathway in a neonatal hypoxic-ischemic encephalopathy rat model

Huang

Doycheva

et al. 2020

J Neuroinflammation

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Background: Inhibition of inositol-requiring enzyme-1 alpha (IRE1α), one of the sensor signaling proteins associated with endoplasmic reticulum (ER) stress, has been shown to alleviate brain injury and improve neurological behavior in a neonatal hypoxic-ischemic encephalopathy (HIE) rat model. However, there is no information about the role of IRE1α inhibitor as well as its molecular mechanisms in preventing neuronal pyroptosis induced by NLRP1 (NOD-, LRR-and pyrin domain-containing 1) inflammasome. In the present study, we hypothesized that IRE1α can degrade microRNA-125-b-2-3p (miR-125-b-2-3p) and activate NLRP1/caspased-1 pathway, and subsequently promote neuronal pyroptosis in HIE rat model. Methods: Ten-day old unsexed rat pups were subjected to hypoxia-ischemia (HI) injury, and the inhibitor of IRE1α, STF083010, was administered intranasally at 1 h after HI induction. AntimiR-125 or NLRP1 activation CRISPR was administered by intracerebroventricular (i.c.v) injection at 24 h before HI induction. Immunofluorescence staining, western blot analysis, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), brain infarct volume measurement, neurological function tests, and Fluoro-Jade C staining were performed. Results: Endogenous phosphorylated IRE1α (p-IRE1α), NLRP1, cleaved caspase-1, interleukin-1β (IL-1β), and interleukin-18 (IL-18) were increased and miR-125-b-2-3p was decreased in HIE rat model. STF083010 administration significantly upregulated the expression of miR-125-b-2-3p, reduced the infarct volume, improved neurobehavioral outcomes and downregulated the protein expression of NLRP1, cleaved caspase-1, IL-1β and IL-18. The protective effects of STF083010 were reversed by antimiR-125 or NLRP1 activation CRISPR. Conclusions: IRE1α inhibitor, STF083010, reduced neuronal pyroptosis at least in part via miR-125/NLRP1/caspase-1 signaling pathway after HI.

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Selective mGluR1 Negative Allosteric Modulator Reduces Blood–Brain Barrier Permeability and Cerebral Edema After Experimental Subarachnoid Hemorrhage

Cited by 55 publications

References 44 publications

Treatment repurposing for inflammatory bowel disease using literature-related discovery and innovation

Treatment repurposing for inflammatory bowel disease using literature-related discovery and innovation

Pituitary Adenylate Cyclase-Activating Polypeptide: A Promising Neuroprotective Peptide in Stroke

IRE1α inhibition attenuates neuronal pyroptosis via miR-125/NLRP1 pathway in a neonatal hypoxic-ischemic encephalopathy rat model

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