Dataset Information

Stereotactic Administration of Edaravone Ameliorates Collagenase-Induced Intracerebral Hemorrhage in Rat.

ABSTRACT:

Background

Edaravone is widely used for treating ischemic stroke, but it is not still confirmed in intracerebral hemorrhage (ICH) as an ideal medication targeting the brain parenchyma. We aimed to investigate the neuroprotective effects of stereotactic administration of edaravone (SI) into the brain parenchyma.

Methods

Intracerebral hemorrhage rat models were established by infusion of collagenase into the caudate nucleus. Neural functional recovery was assessed using modified neurological severity scores (mNSS). A comparative study of therapeutic effects between SI and intraperitoneal injection of edaravone (IP) involved in cerebral edema, blood-brain barrier (BBB) permeability, hematoma absorption, inflammatory response and neuronal apoptosis.

Results

Compared with IP, the mNSS was significantly (P < 0.05) improved by SI; cerebral edema and BBB permeability were dramatically ameliorated (P < 0.05); IL-4 and IL-10 levels increased, but IL-1β and TNF-α levels significantly decreased; neuron apoptosis decreased markedly (P < 0.05); and caspase-3 and Bax expression significantly dropped, but Bcl-2 increased in SI group (P < 0.05).

Conclusion

SI markedly improved neurological deficits in ICH rat models via antiinflammatory and antiapoptosis mechanisms and promoted M2-type microglia differentiation. SI was effective in rats with collagenase-induced ICH.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC5095785 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Publications

Stereotactic Administration of Edaravone Ameliorates Collagenase-Induced Intracerebral Hemorrhage in Rat.

Zhang Yan Y Yang Yang Y Zhang Guang-Zhu GZ Gao Mou M Ge Guang-Zhi GZ Wang Qin-Qin QQ Ji Xin-Chao XC Sun Yi-Lin YL Zhang Hong-Tian HT Xu Ru-Xiang RX

CNS neuroscience & therapeutics 20160708 10

<h4>Background</h4>Edaravone is widely used for treating ischemic stroke, but it is not still confirmed in intracerebral hemorrhage (ICH) as an ideal medication targeting the brain parenchyma. We aimed to investigate the neuroprotective effects of stereotactic administration of edaravone (SI) into the brain parenchyma.<h4>Methods</h4>Intracerebral hemorrhage rat models were established by infusion of collagenase into the caudate nucleus. Neural functional recovery was assessed using modified neu ...[more]

PMID: 27390192

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Project description:AimsIntracerebral hemorrhage (ICH) is a known risk factor for the development of acute symptomatic as well as late unprovoked seizures. The underlying pathophysiology of post-ICH seizures is incompletely understood and there are no reliable predictive biomarkers. An animal model to study post-ICH seizures is currently lacking. The aim of this study was to investigate (1) the occurrence of seizures and interictal epileptiform activity in the ICH rat collagenase model using long-term video-EEG monitoring (VEM) and (2) whether seizure occurrence was associated with interictal epileptiform activity and histological features.MethodsMale Sprague-Dawley rats were implanted with epidural electrodes. After 1 week of baseline VEM, collagenase was injected in left striatum to induce an ICH. VEM was continued for 180 days to assess the occurrence of post-ICH seizures and interictal epileptiform activity (spikes and epileptiform discharges). At the end of the experiment, animals were euthanized for histological characterization of the hemorrhagic lesion, using cresyl violet, Prussian blue and immunofluorescence staining.ResultsAcute symptomatic seizures occurred in 4/12 animals between 46 and 80 h after ICH induction. Late unprovoked seizures were present in 2/12 animals and started at 90 and 103 days post-ICH. Animals with late unprovoked seizures did not have acute symptomatic seizures. All electrographic seizures were accompanied by clear behavioral changes. Interictal spikes and epileptiform discharges were observed in all animals but occurred more frequently in rats with late seizures (p = 0.019 and p < 0.001, respectively). Animals with acute symptomatic seizures had more extended hemorrhagic lesions and hemosiderin deposits in the piriform cortex.ConclusionBoth acute symptomatic and late unprovoked seizures were observed in the rat collagenase model. Interictal epileptiform activity was more frequently seen in animals with late seizures. Rats with acute symptomatic seizures showed more extensive lesions and hemosiderin deposits in the piriform cortex. This model could be used to further explore possible biomarkers for epileptogenesis.

Project description:ObjectiveIntracerebral hemorrhage (ICH) is a subtype of stroke with high mortality and morbidity rates. Our aim was to comprehensively analyze transcriptome and proteome in an experimental ICH model.MethodsAll mice were divided into ICH model (n = 3) and sham groups (n = 3). ICH was induced by collagenase VII. The ipsilateral hemisphere was used for whole transcriptome and proteomics resequencing. After preprocessing, differentially expressed lncRNAs (DElncRNAs), mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and DEproteins between ICH and sham groups were identified. Functional enrichment analysis was performed using the clusterProfiler package, followed by protein-protein interaction (PPI) analysis. After that, the Pearson correlation coefficient between DEmRNAs and DElncRNAs or between DEmRNAs and DEproteins was calculated. DElncRNAs with similar functions were analyzed by the GOSemSim package. After prediction of DEmiRNA-DEmRNA and DElncRNA-DEmiRNA relationships, a competing endogenous RNA (ceRNA) network was constructed. Several DEmRNAs and DElncRNAs were validated in ipsilateral hemisphere tissues of the ICH model and control groups using RT-qPCR and western blot.ResultsBetween the ICH and sham groups, 31 DElncRNAs, 367 DEmRNAs, 35 DEmiRNAs, and 96 DEproteins were identified. DEmRNAs were mainly enriched in inflammation, such as cytokine-cytokine receptor interaction, IL-17, and TNF signaling pathways. A PPI network of DEmRNAs was constructed and hub genes were identified, such as IL6 (degree = 59), TNF (degree = 44), and CXCR2 (degree = 39). 24 DElncRNAs with similar functions were identified, including 15 up- and 9 down-regulated lncRNAs. After integration of DEmiRNA-DEmRNA and DElncRNA-DEmiRNA relationships, we constructed a ceRNA network, composed of 71 DEmRNAs, 17 DEmiRNAs, and 12 DElncRNAs. RT-qPCR and western blot results confirmed that C3, Fga, and Slc4a1 proteins were more lowly expressed and Penk was more highly expressed in ICH than control groups, which could become potential markers for ICH.ConclusionOur findings identified ICH-related DE-RNAs and proteins and potential molecular mechanisms of ICH by transcriptome resequencing and quantitative proteomic analyses.

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Dataset Information

Stereotactic Administration of Edaravone Ameliorates Collagenase-Induced Intracerebral Hemorrhage in Rat.

Background

Methods

Results

Conclusion

Publications

Stereotactic Administration of Edaravone Ameliorates Collagenase-Induced Intracerebral Hemorrhage in Rat.

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