Neurovascular Events After Subarachnoid Hemorrhage: Focusing on Subcellular Organelles

Chen, Sheng; Wu, Haijian; Tang, Jiping; Zhang, Jianmin; Zhang, Junyi

doi:10.1007/978-3-319-04981-6_7

Cited by 50 publications

(25 citation statements)

References 77 publications

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“…Nevertheless, our findings may be consistent with the recent idea of early brain injury as the key pathologic mechanism in SAH 13 . This phenomenon begins immediately after cerebral hemorrhage, and is known to trigger cell death along with mitochondrial dysfunction 14 . Our CSF mitochondrial membrane potential measurements at day 1 after SAH showed significant reduction compared to controls, and recovery in these values at day 3 appear to correspond with patient outcomes.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Mitochondria in Cerebrospinal Fluid and Neurological Recovery After Subarachnoid Hemorrhage

Chou

Lan

Esposito

et al. 2017

Stroke

104

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Background and Purpose Recent studies suggest that extracellular mitochondria may be involved in the pathophysiology of stroke. In this study, we assessed the functional relevance of endogenous extracellular mitochondria in cerebrospinal fluid (CSF) in rats and humans after subarachnoid hemorrhage (SAH). Methods A standard rat model of SAH was used, where an intraluminal suture was used to perforate a cerebral artery, thus leading to blood extravasation into subarachnoid space. At 24 and 72 hrs post-SAH, neurological outcomes were measured, and the standard JC1 assay was used to quantify mitochondrial membrane potentials in the CSF. To further support the rat model experiments, CSF samples were obtained from 41 SAH patients and 27 control subjects. Mitochondrial membrane potentials were measured with the JC1 assay, and correlations with clinical outcomes were assessed at 3 months. Results In the standard rat model of SAH, extracellular mitochondria was detected in CSF at 24 and 72 hrs after injury. JC1 assays demonstrated that mitochondrial membrane potentials in CSF were decreased after SAH compared with sham-operated controls. In human CSF samples, extracellular mitochondria were also detected, and JC1 levels were also reduced after SAH. Furthermore, higher mitochondrial membrane potentials in the CSF was correlated with good clinical recovery at 3 months after SAH onset. Conclusions This proof-of-concept study suggests that extracellular mitochondria may provide a “biomarker-like” glimpse into brain integrity and recovery after injury.

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Section: Discussionmentioning

confidence: 99%

Extracellular Mitochondria in Cerebrospinal Fluid and Neurological Recovery After Subarachnoid Hemorrhage

Chou

Lan

Esposito

et al. 2017

Stroke

104

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“…During EBI, subcellular organelle functions become disordered, and the autophagy-lysosomal system is activated (Chen et al, 2015 ). As the main intracellular recycling system during conditions of starvation and various stressors, autophagy is a critical for neuronal survival (Mizushima and Komatsu, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E-Mimetic Peptide COG1410 Promotes Autophagy by Phosphorylating GSK-3β in Early Brain Injury Following Experimental Subarachnoid Hemorrhage

et al. 2018

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COG1410, a mimetic peptide derived from the apolipoprotein E (apoE) receptor binding region, exerts positive effect on neurological deficits in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH). Currently the neuroprotective effect of COG1410 includes inhibiting BBB disruption, reducing neuronal apoptosis, and neuroinflammation. However, the effect and mechanism of COG1410 to subcellular organelles disorder have not been fully investigated. As the main pathway for recycling long-lived proteins and damaged organelles, neuronal autophagy is activated in SAH and exhibits neuroprotective effects by reducing the insults of EBI. Pharmacologically elevated autophagy usually contributes to alleviated brain injury, while few of the agents achieved clinical transformation. In this study, we explored the activation of autophagy during EBI by measuring the Beclin-1 and LC3B-II protein levels. Administration of COG1410 notably elevated the autophagic markers expression in neurons, simultaneously reversed the neurological deficits. Furthermore, the up-regulated autophagy by COG1410 was further promoted by p-GSK-3β agonist, whereas decreased by p-GSK-3β inhibitor. Taken together, these data suggest that the COG1410 might be a promising therapeutic strategy for EBI via promoting autophagy in SAH.

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“…However, these methods can only reduce a part of occurrence of CVS [22]. Our previous studies have showed that specific knocking down Cx43 in spastic cerebral arteries with specific siRNA interference can significantly alleviate CVS after SAH.…”

Section: Discussionmentioning

confidence: 99%

Identification of OPN, TNC and E-selectin as potential recognition proteins in cerebral vasospasm after subarachnoid hemorrhage

et al. 2016

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Background: Cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is a serious and significant health problem in the worldwide. There are still no effective therapies for treatment of CVS in patients suffering from SAH. Our early studies have demonstrated that the expression of connexin43 (Cx43, a member of gap junctional proteins) in cerebral spastic vessel is significantly up-regulated, and knocking down Cx43 with specific siRNA interference can significantly alleviate CVS after SAH. Therefore, Cx43 in cerebral vessel is a potential target in the treatment of CVS. However, Cx43 is widely distributed in many organs, particularly in the heart, and plays an important role in the physiological function. This study is aimed at identify whether OPN, TNC or E-selectin can be used as a target protein to be recognized in spastic cerebral vessels, then we can produce a carrier containing Cx43 siRNA or other inhibitors as a new potential treatment for CVS. Methods: Twenty eight male Sprague Dawley rats (weighing 300-350 g) were randomly divided into either SAH (n = 16) or sham group (n = 12). The double hemorrhage model was performed on day 0 and 1. All animals were sacrificed after performing India ink angiography on day 5. Initially, the expression of E-selectin, TNC and OPN in cerebral arteries, thoracic aorta and abdominal aorta were analyzed respectively by immunohistochemical staining, western blot in both groups. Then, only those with less expression in thoracic aorta, abdominal aorta and normal cerebral arteries, but higher expression in cerebral spastic arteries were further detected in the spinal cord, heart, kidney, liver, spleen, lung, pancreas, mesenteric and pulmonary arteries, retina and brain tissue, respectively.

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Neurovascular Events After Subarachnoid Hemorrhage: Focusing on Subcellular Organelles

Cited by 50 publications

References 77 publications

Extracellular Mitochondria in Cerebrospinal Fluid and Neurological Recovery After Subarachnoid Hemorrhage

Extracellular Mitochondria in Cerebrospinal Fluid and Neurological Recovery After Subarachnoid Hemorrhage

Apolipoprotein E-Mimetic Peptide COG1410 Promotes Autophagy by Phosphorylating GSK-3β in Early Brain Injury Following Experimental Subarachnoid Hemorrhage

Identification of OPN, TNC and E-selectin as potential recognition proteins in cerebral vasospasm after subarachnoid hemorrhage

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