Inhibition of Blood-Brain Barrier Disruption by an Apolipoprotein E-Mimetic Peptide Ameliorates Early Brain Injury in Experimental Subarachnoid Hemorrhage

Pang, Jinwei; Chen, Yitian; Li, Kuai; Yang, Ping; Peng, Jianhua; Wu, Yue; Chen, Yue; Vitek, Michael P.; Chen, Ligang; Sun, Xiaochuan; Jiang, Yong

doi:10.1007/s12975-016-0507-1

Cited by 74 publications

(58 citation statements)

References 41 publications

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“…In experimental SAH, POSTN caused EBI or BBB disruption via the activation of mitogen-activated protein kinases (MAPKs) and matrix metalloproteinase (MMP)-9, interacting with another matricellular protein tenascin-C [13]. MAPKs and MMP-9 are well known to cause the degradation of cerebral microvessel basal lamina and tight junction protein zona occludens-1, resulting in BBB disruption and brain edema formation after SAH [31,32]. A more recent study also showed the possible involvement of POSTN in the development of EBI or BBB disruption after experimental SAH [28].…”

Section: Discussionmentioning

confidence: 99%

Plasma Periostin and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

et al. 2019

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Delayed cerebral ischemia (DCI) is a serious complication of aneurysmal subarachnoid hemorrhage (SAH). Matricellular protein periostin (POSTN) has been found to be upregulated and linked with early brain injury after experimental SAH. The aim of the present study was to investigate the relationship between plasma POSTN levels and various clinical factors including serum levels of C-reactive protein (CRP), an inflammatory marker, in 109 consecutive SAH patients whose POSTN levels were measured at days 1-12 after aneurysmal obliteration. DCI developed in 16 patients associated with higher incidence of angiographic vasospasm, cerebral infarction, and 90-day worse outcomes. POSTN levels peaked at days 4-6 before DCI development. Cerebrospinal fluid (CSF) drainage was associated with reduced POSTN levels, but did not influence CRP levels. There was no correlation between POSTN levels and other treatments or CRP levels. To predict DCI development, receiver-operating characteristic curves indicated that the most reasonable cutoff POSTN levels were obtained at days 1-3 in patients without CSF drainage (80.5 ng/ml; specificity, 77.6%; sensitivity, 85.7%). Multivariate analyses using variables obtained by day 3 revealed that POSTN level was an independent predictor of DCI. POSTN levels over the cutoff value were associated with higher incidence of DCI, but not angiographic vasospasm. This study shows for the first time that CSF drainage may reduce plasma POSTN levels, and that POSTN levels may increase prior to the development of DCI with and without vasospasm irrespective of systemic inflammatory reactions in clinical settings. These findings suggest POSTN as a new therapeutic molecular target against post-SAH DCI.

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Section: Discussionmentioning

confidence: 99%

Plasma Periostin and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

et al. 2019

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“…We further show that treatment with exogenous apoE mimetic peptides can partially replace endogenous apoE to decrease the BSCB permeability, thus reducing the anatomic and functional deficits in apoE deficient mice after SCI. Previous study show that delivery of exogenous apoE mimetic peptides is able to significantly decrease brain-blood-barrier (BBB) disruption and reduce the neuronal loss and functional deficits after subarachnoid hemorrhage (Pang et al, 2017). These studies suggest that exogenous apoE mimetic peptides could be a novel therapeutic agent to decrease the dysfunction of BSCB or BBB after SCI or other neurological diseases.…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein E as a novel therapeutic neuroprotection target after traumatic spinal cord injury

Cheng

Zheng

et al. 2018

Experimental Neurology

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Apolipoprotein E (apoE), a plasma lipoprotein well known for its important role in lipid and cholesterol metabolism, has also been implicated in many neurological diseases. In this study, we examined the effect of apoE on the pathophysiology of traumatic spinal cord injury (SCI). ApoE-deficient mutant (apoE−/−) and wild-type mice received a T9 moderate contusion SCI and were evaluated using histological and behavioral analyses after injury. At 3 days after injury, the permeability of spinal cord-blood-barrier, measured by extravasation of Evans blue dye, was significantly increased in apoE−/− mice compared to wild type. The inflammation and spared white matter was also significantly increased and decreased, respectively, in apoE−/− mice compared to the wild type ones. The apoptosis of both neurons and oligodendrocytes was also significantly increased in apoE−/− mice. At 42 days after injury, the inflammation was still robust in the injured spinal cord in apoE−/− but not wild type mice. CD45+ leukocytes from peripheral blood persisted in the injured spinal cord of apoE−/− mice. The spared white matter was significantly decreased in apoE−/− mice compared to wild type ones. Locomotor function was significantly decreased in apoE−/− mice compared to wild type ones from week 1 to week 8 after contusion. Treatment of exogenous apoE mimetic peptides partially restored the permeability of spinal cord-blood-barrier in apoE−/− mice after SCI. Importantly, the exogenous apoE peptides decreased inflammation, increased spared white matter and promoted locomotor recovery in apoE−/− mice after SCI. Our results indicate that endogenous apoE plays important roles in maintaining the spinal cord-blood-barrier and decreasing inflammation and spinal cord tissue loss after SCI, suggesting its important neuroprotective function after SCI. Our results further suggest that exogenous apoE mimetic peptides could be a novel and promising neuroprotective reagent for SCI.

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“…Overall, APOE tends to maintain BBB integrity and promote neurological recovery. While APOE-deficiency provokes BBB dysfunction, exogenously administered APOE or its mimetic peptides preserve BBB integrity in experimental studies [197][198][199][200][201][202][203].…”

Section: The Bbb Integrity-promoting Effects Of Astrocytesmentioning

confidence: 99%

Dual roles of astrocytes in plasticity and reconstruction after traumatic brain injury

et al. 2020

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Traumatic brain injury (TBI) is one of the leading causes of fatality and disability worldwide. Despite its high prevalence, effective treatment strategies for TBI are limited. Traumatic brain injury induces structural and functional alterations of astrocytes, the most abundant cell type in the brain. As a way of coping with the trauma, astrocytes respond in diverse mechanisms that result in reactive astrogliosis. Astrocytes are involved in the physiopathologic mechanisms of TBI in an extensive and sophisticated manner. Notably, astrocytes have dual roles in TBI, and some astrocyte-derived factors have double and opposite properties. Thus, the suppression or promotion of reactive astrogliosis does not have a substantial curative effect. In contrast, selective stimulation of the beneficial astrocytederived molecules and simultaneous attenuation of the deleterious factors based on the spatiotemporalenvironment can provide a promising astrocyte-targeting therapeutic strategy. In the current review, we describe for the first time the specific dual roles of astrocytes in neuronal plasticity and reconstruction, including neurogenesis, synaptogenesis, angiogenesis, repair of the blood-brain barrier, and glial scar formation after TBI. We have also classified astrocyte-derived factors depending on their neuroprotective and neurotoxic roles to design more appropriate targeted therapies.

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Inhibition of Blood-Brain Barrier Disruption by an Apolipoprotein E-Mimetic Peptide Ameliorates Early Brain Injury in Experimental Subarachnoid Hemorrhage

Cited by 74 publications

References 41 publications

Plasma Periostin and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Plasma Periostin and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Apolipoprotein E as a novel therapeutic neuroprotection target after traumatic spinal cord injury

Dual roles of astrocytes in plasticity and reconstruction after traumatic brain injury

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