The effect of high mobility group box-1 protein on cerebral edema, blood-brain barrier, oxidative stress and apoptosis in an experimental traumatic brain injury model

Evran, Şevket; Çalış, Fatih; Akkaya, Enes; Baran, Oğuz; Çevik, Serdar; Katar, Salim; Gürevin, Ebru Gürel; Hanımoğlu, Hakan; Hatiboğlu, Mustafa Aziz; Armutak, Elif Ilkay; Karataş, Ersin; Koçyiğit, Abdürrahim; Kaynar, Mehmet

doi:10.1016/j.brainresbull.2019.10.013

Cited by 17 publications

(12 citation statements)

References 64 publications

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“…In the present study, HSYA treatment against TBI were concerned with increased levels of GSH and the ratio of GSH/GSSG, as well as activation of antioxidant enzymes (SOD, CAT) ( Fig. 3), found in agreement with the mechanism of TBI reported earlier 21,22 . Apart from oxidative stress, TLR4, one of main receptors related to inflammation and the pathophysiology of secondary injury following TBI, could trigger the activation of pro-inflammatory signaling pathway, such as NF-κB activation, and subsequently the release of proinflammatory cytokines, such as IL-1β and IL-6 3,21 .…”

Section: Discussionsupporting

confidence: 91%

Hydroxysafflor yellow A acutely attenuates blood-brain barrier permeability, oxidative stress, inflammation and apoptosis in traumatic brain injury in rats1

Tian

Zheng

et al. 2020

Acta Cir. Bras.

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To investigate the therapeutic benefits of Hydroxysafflor yellow A (HSYA) on blood-brain barrier (BBB) vulnerability after traumatic brain injury (TBI) and identify its potential action of mechanisms on TBIinduced injuries. Methods: The rat TBI model was performed by using a controlled cortical impact device. The BBB permeability induced by TBI was measured through Evans Blue dye superflux and western blotting or polymerase chain reaction (PCR) for tight junctional proteins (TJPs). The post-TBI changes in oxidative stress markers, inflammatory response and neuron apoptosis in brain tissue were also tested. Results: Herein, the results showed that HSYA acutely attenuated BBB permeability via increasing the production of the TJPs, including occludin, claudin-1 and zonula occludens protein 24 h after TBI. Additionally, HSYA could suppress the secretion of proinflammatory factors, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α (IL-1β, IL-6, and TNF-α), and also concurrently down-regulate the expression of inflammation-related Toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-kB) protein. These HSYA challenged changes were accompanied by the decreased TBI induced oxidative stress markers and inhibited the expression of apoptosis proteins Bax, caspase-3 and caspase-9. Conclusions: Taken together, all findings suggested that HSYA (30 mg/kg) are against TBI through improving the integrity in BBB, which are associated with the antioxidant, anti-inflammation and antiapoptosis via the probable mechanism of down-regulation of the TLR4/NF-kB pathway, and its in-detail protective mechanisms are under study.

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Section: Discussionsupporting

confidence: 91%

Hydroxysafflor yellow A acutely attenuates blood-brain barrier permeability, oxidative stress, inflammation and apoptosis in traumatic brain injury in rats1

Tian

Zheng

et al. 2020

Acta Cir. Bras.

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“…Immunohistochemical findings and western blot analysis from the TBI model in rodents revealed that Ethyl pyruvate treatment reduced HMGB1, TLR4 and RAGE expression after TBI in the pericontusional cerebral tissue. Moreover, the treatment protected BBB permeability as evidenced by increased Occludin, Claudin-5, and ZO-1 levels of BBB tight junction binding proteins, increased total antioxidant status, decreased total oxidant status and oxidative stress index [60].…”

Section: Hmgb1 Neutralization Against Tbimentioning

confidence: 94%

“…Moreover, the post-traumatic increase of HMGB1 has been shown to negatively affect other secondary post-traumatic damage processes by promoting apoptosis, as shown by increased Bax protein and caspase-3, and decreased Bcl-2. In respect to the relationship between post-traumatic HMGB1 up-regulation and oxidative stress, a reduced total antioxidant status (TAS) and increased total oxidant status (TOS) along with elevated oxidative stress index (OSI) have been observed [60].…”

Section: Hmgb1-mediated Neuroinflammatory Response In Tbimentioning

confidence: 99%

HMGB1-Mediated Neuroinflammatory Responses in Brain Injuries: Potential Mechanisms and Therapeutic Opportunities

Paudel

Angelopoulou

Piperi

et al. 2020

IJMS

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Brain injuries are devastating conditions, representing a global cause of mortality and morbidity, with no effective treatment to date. Increased evidence supports the role of neuroinflammation in driving several forms of brain injuries. High mobility group box 1 (HMGB1) protein is a pro-inflammatory-like cytokine with an initiator role in neuroinflammation that has been implicated in Traumatic brain injury (TBI) as well as in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Herein, we discuss the implication of HMGB1-induced neuroinflammatory responses in these brain injuries, mediated through binding to the receptor for advanced glycation end products (RAGE), toll-like receptor4 (TLR4) and other inflammatory mediators. Moreover, we provide evidence on the biomarker potential of HMGB1 and the significance of its nucleocytoplasmic translocation during brain injuries along with the promising neuroprotective effects observed upon HMGB1 inhibition/neutralization in TBI and EBI induced by SAH. Overall, this review addresses the current advances on neuroinflammation driven by HMGB1 in brain injuries indicating a future treatment opportunity that may overcome current therapeutic gaps.

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“…The upregulation of Bcl2 has been associated with ameliorated ischemic brain injury in experimental stroke (Yang et al, 2017). Also, increased antiapoptotic Bcl2 expression has been used as a marker of improved neurological function, bloodbrain barrier impairment, neurodegeneration, and brain edema (Fang et al, 2018;Evran et al, 2020), thus supporting the neuroprotective benefits of this pathway.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicle-Derived microRNA-410 From Mesenchymal Stem Cells Protects Against Neonatal Hypoxia-Ischemia Brain Damage Through an HDAC1-Dependent EGR2/Bcl2 Axis

Han

Yang

Hao

et al. 2021

Front. Cell Dev. Biol.

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Hypoxia-ischemia brain damage (HIBD) is a neurological disorder occring in neonates, which is exacerbated by neuronal apoptosis. Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been proposed as a promising strategy for treating or preventing ischemia-related diseases. However, their mechanisms in HIBD remain unclear. Thus, we aimed to address the role of EV-derived microRNA (miR)-410 in HIBD. Neonatal HIBD mouse model was constructed using HI insult, from which neurons were isolated, followed by exposure to oxygen glucose deprivation (OGD). EVs were isolated from human umbilical cord (hUC)-derived MSCs. In silico analyses, dual-luciferase reporter gene and chromatin immunoprecipitation assays were adopted to determine relationships among miR-410, histone deacetylase 1 (HDAC1), early growth response protein 2 (EGR2), and B cell lymphoma/leukemia 2 (Bcl2). The functional roles of EV-derived miR-410 were determined using loss- and gain-of functions experiments, and by evaluating neuronal viability, cell-cycle distribution and neuronal apoptosis in vitro as well as modified neurological severity score (mNSS), edema formation, and cerebral infarction volume in vivo. hUC-MSCs-derived EVs protected against HIBD in vivo and inhibited the OGD-induced neuronal apoptosis in vitro. miR-410 was successfully delivered to neurons by hUC-MSCs-EVs and negatively targeted HDAC1, which inversely mediated the expression of EGR2/Bcl2. Upregulation of EV-derived miR-410 promoted the viability but inhibited apoptosis of neurons, which was reversed by HDAC1 overexpression. EV-derived miR-410 elevation reduced mNSS, edema formation, and cerebral infarction volume by increasing EGR2/Bcl2 expression through downregulating HDAC1 expression in vivo. In summary, EV-derived miR-410 impeded neuronal apoptosis by elevating the expression of EGR2/Bcl2 via HDAC1 downregulation, thereby providing a potential strategy for treating or preventing HIBD.

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The effect of high mobility group box-1 protein on cerebral edema, blood-brain barrier, oxidative stress and apoptosis in an experimental traumatic brain injury model

Cited by 17 publications

References 64 publications

Hydroxysafflor yellow A acutely attenuates blood-brain barrier permeability, oxidative stress, inflammation and apoptosis in traumatic brain injury in rats1

Hydroxysafflor yellow A acutely attenuates blood-brain barrier permeability, oxidative stress, inflammation and apoptosis in traumatic brain injury in rats1

HMGB1-Mediated Neuroinflammatory Responses in Brain Injuries: Potential Mechanisms and Therapeutic Opportunities

Extracellular Vesicle-Derived microRNA-410 From Mesenchymal Stem Cells Protects Against Neonatal Hypoxia-Ischemia Brain Damage Through an HDAC1-Dependent EGR2/Bcl2 Axis

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