Controversies and evolving new mechanisms in subarachnoid hemorrhage

Chen, Sheng; Feng, Hua; Sherchan, Prativa; Klebe, Damon; Zhao, Gang; Sun, Xiaochuan; Zhang, Jianmin; Tang, Jiping; Zhang, Junyi

doi:10.1016/j.pneurobio.2013.09.002

Cited by 319 publications

(272 citation statements)

References 488 publications

(555 reference statements)

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“…28,29 Both of them usually develop brain edema, which is a major independent risk factor for death and a poor outcome after SAH. 30 Both neuronal apoptosis and BBB rupture were observed at 24 hours after SAH in our present work, which may be the cause of increased brain water content. Further researches were in urgent need to explore a key factor in the development of apoptosis in brain research.…”

Section: Strokesupporting

confidence: 54%

Peroxisome Proliferator–Activated Receptor β/δ Alleviates Early Brain Injury After Subarachnoid Hemorrhage in Rats

Teng

Jiang

et al. 2016

Stroke

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S ubarachnoid hemorrhage (SAH) is a devastating disease with high mortality and disability. Traditionally, cerebral vasospasm, which develops in large cerebral arteries 3 to 7 days after SAH, was considered the most crucial cause of serious consequences after SAH. However, recent studies have shown that there is little advance in improving the outcome of SAH by prevention of vasospasm. It is reported that 12% of SAH patients die before receiving medical attention and 33% within 48 hours of SAH and 50% survivors havepermanent disability.1 The primary determinant of poor outcome in SAH patients was proposed to be early brain injury (EBI).2,3 EBI was described as the immediate injury of the brain after SAH, including elevation of intracranial pressure, disruption of bloodbrain barrier (BBB), neuronal cell death, brain edema, and other pathophysiologic changes. 4,5 Several recent studies have indicated apoptosis might play an important role in the pathogenesis of EBI after SAH. 6Background and Purpose-Early brain injury is proposed to be the primary cause of the poor outcome after subarachnoid hemorrhage (SAH), which is closely related to the neural apoptosis. To date, the relationship between peroxisome proliferator-activated receptor β/δ (PPARβ/δ) and nuclear factor-κB/matrix metalloproteinase-9 (NF-κB/MMP-9) pathway, both of which are closely related to apoptotic effects, has been poorly studied in SAH. The present study was undertaken to evaluate the effects of PPARβ/δ on early brain injury and NF-κB/MMP-9 pathway after SAH in rats. Methods-SAH model was established by injecting nonheparinized autologous arterial blood into the prechiasmatic cistern in male Sprague-Dawley rats. Adenoviruses or small interfering RNAs were injected into the right lateral cerebral ventricle to, respectively, up-or downregulate PPARβ/δ expression before SAH. All animals were assessed with a neurological score and then killed at 24 hours after SAH surgery. The indexes of brain water content, blood-brain barrier permeability, and apoptosis were used to detect brain injury. The expression of PPARβ/δ, NF-κB, and MMP-9 were measured by immunohistochemistry, gelatin zymography, and Western Blot methods, respectively. In addition, GW0742, a specific agonist of PPARβ/δ, was used to treat SAH in rats, the effects of which were evaluated by neurological scoring and Evans blue extravasation. Results-Overexpression of PPARβ/δ by adenoviruses treatment significantly ameliorated brain injury with improvement in neurological deficits, brain edema, blood-brain barrier impairment, and neural cell apoptosis at 24 hours after SAH in rats, whereas downregulation of PPARβ/δ by small interfering RNAs administration resulted in the reverse effects of the above. The expression levels of NF-κB and MMP-9 were markedly downregulated when PPARβ/δ increased after PPARβ/δ adenovirus transfection and upregulated when PPARβ/δ decreased by PPARβ/δ small interfering RNAs treatment. Moreover, GW0742 improved neurological deficits and reduced Evans blue extravasation ...

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Section: Strokesupporting

confidence: 54%

Peroxisome Proliferator–Activated Receptor β/δ Alleviates Early Brain Injury After Subarachnoid Hemorrhage in Rats

Teng

Jiang

et al. 2016

Stroke

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“…[4][5][6][7][8] Theoretically, these post-hemorrhagic cascades and products may contribute to further vascular ischemia and neuronal injury. [9][10][11] High mobility group box 1(HMGB1) is a nuclear factor that has been identified as an important immune mediator, triggering the production of various inflammatory cytokines in many diseases.…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid high mobility group box 1 is associated with neuronal death in subarachnoid hemorrhage

Wang

Tang

Lee

et al. 2016

J Cereb Blood Flow Metab

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We aim to determine the cerebrospinal fluid levels of high mobility group box 1 in subarachnoid hemorrhage patients and to investigate the involvement of the receptor for advanced glycation end products and high mobility group box 1 in the pathogenesis of post-subarachnoid hemorrhage neuronal death. The study included 40 patients (mean age, 59 AE 19 years) with Fisher's grade ! III aneurysmal subarachnoid hemorrhage. Cerebrospinal fluid was collected on the seventh day post-hemorrhage. Receptor for advanced glycation end products expression was examined in rat brain tissue following subarachnoid hemorrhage and in cultured neurons exposed to post-subarachnoid hemorrhage cerebrospinal fluid. Therapeutic effects of the recombinant soluble form of RAGE on subarachnoid hemorrhage models were also investigated. The results indicated that a higher level of cerebrospinal fluid high mobility group box 1 was independently associated with unfavorable outcome at three months post-subarachnoid hemorrhage (OR ¼ 1.061, 95% CI: 1.005-1.121). Expression of RAGE increased in post-subarachnoid hemorrhage rat brain cells and in cultured neuron with stimulation of post-subarachnoid hemorrhage cerebrospinal fluid. Administration of recombinant soluble form of RAGE significantly reduced the number of positive TUNEL staining cells in subarachnoid hemorrhage rat and improved cell viability in post-subarachnoid hemorrhage cerebrospinal fluid-treated cultured neurons. Thus, the level of cerebrospinal fluid high mobility group box 1 can be a prognostic indicator for patients with Fisher's grade ! III aneurysmal subarachnoid hemorrhage and that treatment with soluble form of RAGE is a novel approach for subarachnoid hemorrhage.

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“…[3][4][5] In both animal and clinical studies, the severity of bleeding and the extent of decreased CBF correlated with neurological outcome [6][7][8] ; however, how and to what extent the initial global ischemia or subsequent elevated ICP contribute to early brain injury remains poorly understood. [3][4][5] A feasible way to reduce elevated ICP is decompressive craniectomy (DC), a technique that dates back more than a century. 9 In recent years, both animal and clinical studies reported beneficial effects of DC for treating conditions, such as traumatic brain injury 10,11 and malignant middle cerebral artery (MCA) infarction.…”

mentioning

confidence: 99%

Effect of Decompressive Craniectomy on Outcome Following Subarachnoid Hemorrhage in Mice

Bühler

Azghandi

Schüller

et al. 2015

Stroke

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Subarachnoid hemorrhage (SAH) is a stroke subtype associated with high mortality and morbidity as a result of early and delayed ischemic processes. Nearly one quarter of all patients with SAH die shortly after hemorrhage because of elevated intracranial pressure (ICP) and the resulting global cerebral ischemia.1,2 Hospitalized patients further experience severe complications, including rebleeding, early brain injury, and delayed cerebral ischemia, which together contribute to a devastatingly high 1-month mortality rate of 50%. 1,2 Early brain injury is the predominant cause of death after SAH and is characterized by elevated ICP, decreased cerebral blood flow (CBF), and global cerebral ischemia resulting in secondary injuries, including disruption of the blood-brain barrier, inflammation, and oxidative stress, which all cause neuronal cell death. [3][4][5] In both animal and clinical studies, the severity of bleeding and the extent of decreased CBF correlated with neurological outcome [6][7][8] ; however, how and to what extent the initial global ischemia or subsequent elevated ICP contribute to early brain injury remains poorly understood. [3][4][5] A feasible way to reduce elevated ICP is decompressive craniectomy (DC), a technique that dates back more than a century. 9 In recent years, both animal and clinical studies reported beneficial effects of DC for treating conditions, such as traumatic brain injury 10,11 and malignant middle cerebral artery (MCA) infarction. 12,13 With respect to SAH, however, relatively few studies have been published regarding the application of DC and its effect on outcome; moreover, the results published to date are contradictory and controversial. [14][15][16][17][18] To address these questions, we performed DC to evaluate the role of SAH-induced elevated ICP and subsequent global ischemia and to investigate whether DC may serve as a therapeutic option for SAH using a standardized animal model. MethodsIn total, 41 male C57BL/6 mice (22-25 g; Charles River Laboratories, Sulzfeld, Germany) were used. All experiments were approved by the Government of Upper Bavaria (protocol number 55.2.1.54-2532-90-13) and were performed in accordance with standard ethical guidelines. Experimental DesignInitially, 40 animals were assigned randomly to the following 4 experimental groups: sham surgery, SAH, DC after SAH, and DC before SAH (Figure 1). All assessments were performed by an Background and Purpose-Elevated intracranial pressure (ICP) is a key feature of subarachnoid hemorrhage (SAH). Here, we examined the role of elevated ICP in the pathophysiology of SAH, and we investigated whether decreasing ICP by performing decompressive craniectomy (DC) can improve outcome. Methods-SAH was induced in male C57BL/6 mice via endovascular Circle of Willis perforation in the following 4 groups:sham surgery, SAH, DC after SAH, and DC before SAH. DC was performed either 15 minutes before or after SAH induction. ICP, cerebral blood flow, heart rate, oxygen saturation, and end-tidal PCO 2 were monitored for ...

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Controversies and evolving new mechanisms in subarachnoid hemorrhage

Cited by 319 publications

References 488 publications

Peroxisome Proliferator–Activated Receptor β/δ Alleviates Early Brain Injury After Subarachnoid Hemorrhage in Rats

Peroxisome Proliferator–Activated Receptor β/δ Alleviates Early Brain Injury After Subarachnoid Hemorrhage in Rats

Cerebrospinal fluid high mobility group box 1 is associated with neuronal death in subarachnoid hemorrhage

Effect of Decompressive Craniectomy on Outcome Following Subarachnoid Hemorrhage in Mice

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