Therapeutic strategy against ischemic stroke with the concept of neurovascular unit

Ozaki, Tomohiko; Nakamura, Hajime; Kishima, Haruhiko

doi:10.1016/j.neuint.2019.03.022

Cited by 37 publications

(29 citation statements)

References 101 publications

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“…Previous studies have reported that the incidence of early mortality following ischemic stroke (between 21 days to 1 month) in both high-income and low-middle-income countries increased gradually from 2000 to 2008, from 13 to 23% and 13 to 19%, respectively (3,4). currently, intravenous thrombolysis and mechanical thrombectomy are the only effective means of treating ischemic stroke (5,6); however, these treatment options are limited by the short-recommended treatment window (6). in addition, a series of reperfusion injuries may occur following ischemic reperfusion (6,7); in particular, inflammation and oxidative stress are the main causes of reperfusion injuries, and the latter can induce the former (6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Modulators of microglia activation and polarization in ischemic stroke (Review)

et al. 2020

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ischemic stroke is one of the leading causes of mortality and disability worldwide. However, there is a current lack of effective therapies available. as the resident macrophages of the brain, microglia can monitor the microenvironment and initiate immune responses. in response to various brain injuries, such as ischemic stroke, microglia are activated and polarized into the proinflammatory M1 phenotype or the anti-inflammatory M2 phenotype. The immunomodulatory molecules, such as cytokines and chemokines, generated by these microglia are closely associated with secondary brain damage or repair, respectively, following ischemic stroke. it has been shown that M1 microglia promote secondary brain damage, whilst M2 microglia facilitate recovery following stroke. in addition, autophagy is also reportedly involved in the pathology of ischemic stroke through regulating the activation and function of microglia. Therefore, this review aimed to provide a comprehensive overview of microglia activation, their functions and changes, and the modulators of these processes, including transcription factors, membrane receptors, ion channel proteins and genes, in ischemic stroke. The effects of autophagy on microglia polarization in ischemic stroke were also reviewed. Finally, future research areas of ischemic stroke and the implications of the current knowledge for the development of novel therapeutics for ischemic stroke were identified. Contents 1. introduction 2. Microglia 3. Modulatory mechanisms of microglia polarization 4. autophagy 5. conclusions

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Section: Introductionmentioning

confidence: 99%

Modulators of microglia activation and polarization in ischemic stroke (Review)

et al. 2020

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“…The PPAR signaling pathway is related to energy metabolism [ 47 ]. After IS, neurovascular units (which includes the neurons, blood-brain barrier, microglia, and extracellular matrix components; there is a wide range of signal connections between them, which is the material basis for ensuring neuron function and normal cerebral blood flow) play a very important role in the pathophysiology and clinical treatment of IS [ 48 – 50 ]. The neurons, blood-brain barrier, and microglia are intertwined through various cascade response signaling pathways after ischemia and hypoxia to jointly promote the occurrence, development, and outcome of IS [ 51 , 52 ].…”

Section: Resultsmentioning

confidence: 99%

The Effect of Hedysarum multijugum Maxim.-Chuanxiong rhizoma Compound on Ischemic Stroke: A Research Based on Network and Experimental Pharmacology

Yang

Zeng

et al. 2020

Oxidative Medicine and Cellular Longevity

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Background. Hedysarum multijugum Maxim.-Chuanxiong rhizoma compound (HCC) is a common herbal formula modified from Buyang Huanwu decoction. Clinical trials have demonstrated its therapeutic potential for ischemic stroke (IS). However, the mechanism of HCC remains unclear. Methods. The HCC’s components were collected from the TCMSP database and TCM@Taiwan database. After that, the HCC’s compound targets were predicted by PharmMapper. The IS-related genes were obtained from GeneCards, and OMIM and the protein-protein interaction (PPI) data of HCC’s targets and IS genes were obtained from the String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis and the Cytoscape 3.7.2 was utilized to construct and analyze the networks. Finally, a series of animal experiments were carried out to validate the prediction results of network pharmacology. The expressions of GRP78, p-PERK, and CHOP proteins and mRNAs in different time periods after HCC intervention were detected by Western blot, immunohistochemistry, and RT-qPCR. Results. A total of 440 potential targets and 388 IS genes were obtained. The results of HCC-IS PPI network analysis showed that HCC may regulate IS-related targets (such as ALB, AKT1, MMP9, IGF1, and CASP3), biological processes (such as endoplasmic reticulum stress, inflammation modules, hypoxia modules, regulation of neuronal apoptosis and proliferation, and angiogenesis), and signaling pathways (such as PI3K-Akt, FoxO, TNF, HIF-1, and Rap1 signaling). The animal experiments showed that HCC can improve the neurobehavioral scores and protect the neurons of IS rats ( P < 0.05 ). HCC inhibited the expression of p-PERK in the PERK pathway from 12 h after surgery, significantly promoted the expression of GRP78 protein, and inhibited the expression of CHOP protein after surgery, especially at 24 h after surgery ( P < 0.05 ). The results of RT-qPCR showed that HCC can significantly reduce the expression of CHOP mRNA in the neurons in the CA1 region of the hippocampus 72 h after MCAO ( P < 0.05 ). Conclusion. HCC may achieve a role in the treatment of IS by intervening in a series of targets, signaling pathways, and biological processes such as inflammation, oxidative stress, endoplasmic reticulum stress, and angiogenesis.

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“…Tight junctions, which play an essential role in maintaining BBB integrity, are structures formed by at least three different types of transmembrane proteins, such as occludin, claudin and junctional adhesive molecule [7,8]. BMECs, along with neurons, pericytes, astrocytes, microglial cells, and extracellular matrix, constitute a functional network known as the neurovascular unit [9,10], Figure 1 show the cellular constituents and transport pathways of the BBB [11]. Due to the tight barrier, a number of drugs are unable to penetrate the BBB and produce therapeutic effects in the CNS [12].…”

Section: Introductionmentioning

confidence: 99%

Recent Progress in Microfluidic Models of the Blood-Brain Barrier

Jiang

Zheng

et al. 2019

Micromachines

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The blood-brain barrier (BBB) is a critical physical and chemical barrier that maintains brain homeostasis. Researchers in academia and industry are highly motivated to develop experimental models that can accurately mimic the physiological characteristics of the BBB. Microfluidic systems, which manipulate fluids at the micrometer scale, are ideal tools for simulating the BBB microenvironment. In this review, we summarized the progress in the design and evaluation of microfluidic in vitro BBB models, including advances in chip materials, porous membranes, the use of endothelial cells, the importance of shear stress, the detection specific markers to monitor tight junction formation and integrity, measurements of TEER and permeability. We also pointed out several shortcomings of the current microfluidic models. The purpose of this paper is to let the readers understand the characteristics of different types of model design, and select appropriate design parameters according to the research needs, so as to obtain the best experimental results. We believe that the microfluidics BBB models will play an important role in neuroscience and pharmaceutical research.

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Therapeutic strategy against ischemic stroke with the concept of neurovascular unit

Cited by 37 publications

References 101 publications

Modulators of microglia activation and polarization in ischemic stroke (Review)

Modulators of microglia activation and polarization in ischemic stroke (Review)

The Effect of Hedysarum multijugum Maxim.-Chuanxiong rhizoma Compound on Ischemic Stroke: A Research Based on Network and Experimental Pharmacology

Recent Progress in Microfluidic Models of the Blood-Brain Barrier

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