Intracerebral Hemorrhage as an Axonal Tract Injury Disorder with Inflammatory Reactions

Katsuki, Hiroshi

doi:10.1248/bpb.b16-01013

Cited by 20 publications

(13 citation statements)

References 36 publications

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“…Melatonin has a role in sleep regulation, shows antioxidant effects due to upregulation of some antioxidant enzymes, and is a potent reactive oxygen species scavenger [7,8]. The administration of melatonin in animal models with SIH has been associated with beneficial effects, such as the reduction of oxidative damage and motor dysfunction [9,10]. Previously, we found a higher oxidative state in non-survivor SIH patients than in survivor patients, as assessed by serum concentrations of malondialdehyde [11] (biomarker of lipid peroxidation) [12,13].…”

Section: Introductionmentioning

confidence: 99%

The Serum Melatonin Levels and Mortality of Patients with Spontaneous Intracerebral Hemorrhage

et al. 2019

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Objective: Providing melatonin in animal models with spontaneous intracerebral hemorrhage (SIH) has been associated with beneficial effects. However, to our knowledge, there are no published data on circulating melatonin levels regarding the prognosis of SIH patients. Therefore, the objectives of this study were to determine whether serum melatonin levels in SIH patients were associated with early mortality and whether they could be used as prognostic biomarkers. Methods: This observational and prospective study included patients with supratentorial and clinically severe SIH (defined as Glasgow Coma Scale GCS <9) admitted to the Intensive Care Units of six Spanish hospitals. Serum melatonin levels were determined at the time of severe SIH diagnosis. Mortality at 30 days was the study end-point. Results: Non-surviving patients (n = 46) showed higher serum melatonin levels (p < 0.001) than surviving (n = 54) patients. An area under the curve was found for the prediction of 30-day mortality by serum melatonin levels of 0.89 (95% CI = 0.81–0.94; p < 0.001). Multiple logistic regression analysis showed an association of serum melatonin levels with 30-day mortality (Odds Ratio = 8.16; 95% CI = 2.30–28.95; p = 0.001) after controlling for midline shift, glycemia, early evacuation of SIH, and Intracerebral hemorrhage (ICH) score. Conclusions: The novel findings by our study were the presence of higher serum melatonin levels in non-surviving patients than in surviving patients and the association of these levels with mortality.

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Section: Introductionmentioning

confidence: 99%

The Serum Melatonin Levels and Mortality of Patients with Spontaneous Intracerebral Hemorrhage

et al. 2019

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“…Studies in both human patients with ICH and rat models of ICH show that the invasion of the hematoma into the internal capsule can cause axonal dysfunction, which would greatly aggravate the severity of symptoms after ICH. The blood‐derived protease thrombin may play a key role in the acute phase of axonal tract injury after ICH in the internal capsule through fragmentation of axonal structures, inducing axonal transport dysfunction . Therefore, axon regeneration is also a potential treatment.…”

Section: Repair or Recovery Mechanism And Strategymentioning

confidence: 99%

“…The blood-derived protease thrombin may play a key role in the acute phase of axonal tract injury after ICH in the internal capsule through fragmentation of axonal structures, inducing axonal transport dysfunction. 94 Therefore, axon regeneration is also a potential treatment.…”

Section: Axon Regenerationmentioning

confidence: 99%

White matter repair and treatment strategy after intracerebral hemorrhage

et al. 2019

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The predilection site of intracerebral hemorrhage (ICH) is in the basal ganglia, which is rich in white matter (WM) fiber bundles, such as cerebrospinal tract in the internal capsule. ICH induced damage to this area can easily lead to severe neurological dysfunction and affects the prognosis and quality of life of patients. At present, the pathophysiological mechanisms of white matter injury (WMI) after ICH have attracted researchers' attention, but studies on the repair and recovery mechanisms and therapy strategies remain rare. In this review, we mainly summarized the WM recovery and treatment strategies after ICH by updating the WMI‐related content by reviewing the latest researches and proposing the bottleneck of the current research.

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“…As a member of the nuclear receptor superfamily, RARa exhibits a variety of biological effects by binding to corresponding ligands, thus regulating the transcription of target genes (14). Tamibarotene (Am80), a selective agonist of RARa, has been shown to exert significant inhibitory effects on neuroinflammation after ischemic stroke and intracranial hemorrhage (ICH) (14)(15)(16)(17), thus suggesting the suitability of targeting RARa as a form of stroke therapy. However, the role of Am80 in anti-neuroinflammation has not been reported for EBI after SAH.…”

Section: Introductionmentioning

confidence: 99%

Activation of RARα Receptor Attenuates Neuroinflammation After SAH via Promoting M1-to-M2 Phenotypic Polarization of Microglia and Regulating Mafb/Msr1/PI3K-Akt/NF-κB Pathway

Tian

Liu

et al. 2022

Front. Immunol.

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Background and PurposeSubarachnoid hemorrhage (SAH) is a life-threatening subtype of stroke with high rates of mortality. In the early stages of SAH, neuroinflammation is one of the important mechanisms leading to brain injury after SAH. In various central nervous system diseases, activation of RARα receptor has been proven to demonstrate neuroprotective effects. This study aimed to investigate the anti-inflammatory effects of RARα receptor activation after SAH.MethodsInternal carotid artery puncture method used to established SAH model in Sprague-Dawley rats. The RARα specific agonist Am80 was injected intraperitoneally 1 hour after SAH. AGN196996 (specific RARα inhibitor), Msr1 siRNA and LY294002 (PI3K-Akt inhibitor) were administered via the lateral ventricle before SAH. Evaluation SAH grade, neurological function score, blood-brain barrier permeability. BV2 cells and SH-SY5Y cells were co-cultured and stimulated by oxyhemoglobin to establish an in vitro model of SAH. RT-PCR, Western blotting, and immunofluorescence staining were used to investigate pathway-related proteins, microglia activation and inflammatory response. Results: The expression of RARα, Mafb, and Msr1 increased in rat brain tissue after SAH. Activation of the RARα receptor with Am80 improved neurological deficits and attenuated brain edema, blood brain barrier permeability. Am80 increased the expression of Mafb and Msr1, and reduced neuroinflammation by enhancing the phosphorylation of Akt and by inhibiting the phosphorylation of NF-κB. AGN196996, Msr1 siRNA, and LY294002 reversed the therapeutic effects of Am80 by reducing the expression of Msr1 and the phosphorylation of Akt. In vitro model of SAH, Am80 promoted M1-to-M2 phenotypic polarization in microglia and suppressed the nuclear transcription of NF-κB.ConclusionActivation of the RARα receptor attenuated neuroinflammation by promoting M1-to-M2 phenotypic polarization in microglia and regulating the Mafb/Msr1/PI3K-Akt/NF-κB pathway. RARα might serve as a potential target for SAH therapy.

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Intracerebral Hemorrhage as an Axonal Tract Injury Disorder with Inflammatory Reactions

Cited by 20 publications

References 36 publications

The Serum Melatonin Levels and Mortality of Patients with Spontaneous Intracerebral Hemorrhage

The Serum Melatonin Levels and Mortality of Patients with Spontaneous Intracerebral Hemorrhage

White matter repair and treatment strategy after intracerebral hemorrhage

Activation of RARα Receptor Attenuates Neuroinflammation After SAH via Promoting M1-to-M2 Phenotypic Polarization of Microglia and Regulating Mafb/Msr1/PI3K-Akt/NF-κB Pathway

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