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Quantitative proteomic analysis of intracerebral hemorrhage in rats with a focus on brain energy metabolism.

ABSTRACT: INTRODUCTION:Intracerebral hemorrhage (ICH) is a lethal cerebrovascular disorder with a high mortality and morbidity. The pathophysiological mechanisms underlying ICH-induced secondary injury remain unclear. METHODS:To examine one of the gaps in the knowledge about ICH pathological mechanisms, isobaric tag for relative and absolute quantification (iTRAQ)-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used in collagenase-induced ICH rats on the 2nd day. RESULTS:A total of 6,456 proteins were identified with a 1% false discovery rate (FDR). Of these proteins, 126 and 75 differentially expressed proteins (DEPs) were substantially increased and decreased, respectively. Based on Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and STRING analyses, the protein changes in cerebral hemorrhage were comprehensively evaluated, and the energy metabolism in ICH was anchored. The core position of the nitrogen metabolism pathway in brain metabolism in ICH was found for the first time. Carbonic anhydrase 1 (Ca1), carbonic anhydrase 2 (Ca2), and glutamine synthetase (Glul) participated in this pathway. We constructed the protein-protein interaction (PPI) networks for the energy metabolism of ICH, including the Atp6v1a-Atp6v0c-Atp6v0d1-Ppa2-Atp6ap2 network. CONCLUSIONS:It seems that dysregulation of energy metabolism, especially nitrogen metabolism, may be a major cause in secondary ICH injury. This information provides novel insights into secondary events following ICH.

SUBMITTER: Liu T

PROVIDER: S-EPMC6236229 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Quantitative proteomic analysis of intracerebral hemorrhage in rats with a focus on brain energy metabolism.

Liu Tao T Zhou Jing J Cui Hanjin H Li Pengfei P Li Haigang H Wang Yang Y Tang Tao T

Brain and behavior 20181011 11

<h4>Introduction</h4>Intracerebral hemorrhage (ICH) is a lethal cerebrovascular disorder with a high mortality and morbidity. The pathophysiological mechanisms underlying ICH-induced secondary injury remain unclear.<h4>Methods</h4>To examine one of the gaps in the knowledge about ICH pathological mechanisms, isobaric tag for relative and absolute quantification (iTRAQ)-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used in collagenase-induced ICH rats on the 2nd day.<h4>Resu ...[more]

PMID: 30307711

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Project description:Intracerebral hemorrhage (ICH) prognostication during the acute phase is often subjective among physicians and often affects treatment decisions. The present study explores objective imaging parameters using quantitative corticospinal tract (CST) fiber reconstruction during the acute phase of ICH and correlates these parameters with functional outcome and patient recovery. We prospectively enrolled nonsurgical spontaneous supratentorial ICH patients and obtained an MRI scan on day 5 ± 1. Q-space diffeomorphic reconstruction was performed using DSI Studio, and quantitative anisotropy (QA) was calculated. The CST was reconstructed based on QA. The dichotomized modified Rankin Scale score on day 90 (favorable outcome = 0-2) and Barthel Index (favorable recovery = 100 on day 90 or improvement between discharge and day 90 > 60%) were assessed. Thirty-three patients, median age 72 years (interquartile range (IQR) 64-83), 21 female (64%), 21 (64%) with lobar hemorrhage, median ICH volume on admission 15.0 (IQR 7.0-27.4) mL, were included. Sixteen patients (48%) had a favorable outcome and 24 (73%) had a favorable recovery. The mean number of ipsilesional reconstructed CST fiber pathways was higher in patients with favorable outcomes (153 (standard deviation (SD) 103) vs. 60 (SD 39), p = 0.003) and predicted outcome after adjustment (Exp(B) = 1.016 (95% CI = 1.002-1.030)). QA in the ipsilesional posterior limb of the internal capsule showed a trend towards an association with favorable outcome (Exp(B) = 1.194 (95% CI = 0.991-1.439 (adjusted))). The total (ipsilesional + contralesional) number of reconstructed fiber pathways was associated with favorable recovery (Exp(B) = 1.025 (95% CI = 1.003-1.047 (adjusted))). Quantitative tractography parameters assessed in the acute phase of ICH may represent a promising predictor of long-term outcome and recovery. This might facilitate prognostic evaluation and organization of rehabilitation.

Project description:The mechanisms underlying intracerebral hemorrhage (ICH)-related cognitive impairment (CI) remain unclear. Long-term structural and functional changes were investigated in the brains of healthy male and female Wistar rats after experimental ICH. Following double injection of autologous blood, rats underwent short-term (onset, 3 and 7 days) and long-term (3 and 6 months) radiological assessment and behavioral tests exploring spontaneous locomotion, anxiety-like behavior and working memory, spatial recognition memory and visual recognition memory. Volumetric and metabolic changes in brain areas were examined by 7Tesla-MRI and [18F] FDG-PET, respectively. Brain connectomic disorders and maladaptive processes were seeked through brain metabolic connectivity analysis and atrophy-related network analysis. From an initial hematoma mean volume of 23.35 ± 9.50 mm3, we found early spontaneous locomotor recovery and significant spontaneous blood resorption (≈ 40% of the initial lesion) from days 0 to 7. After 3 and 6 months, ICH rats exhibited CI in several domains as compared to the sham group (working memory: 58.1 ± 1.2 vs. 70.7 ± 1.2%, p < 0.001; spatial recognition memory: 48.7 ± 1.9 vs. 64 ± 1.8%, p < 0.001 and visual recognition memory: 0.14 ± 0.05 vs. 0.33 ± 0.04, p = 0.013, in female only). Rats that experienced ICH had remote and concomitant cerebral atrophy and hypometabolism of ipsilateral striatum, thalamus, limbic system and cortical areas (temporal and parietal lobes). Interestingly, both structural and metabolic deterioration was found in the limbic system connected to the affected site, but remotely from the initial insult. On the other hand, increased activity and functional connectivity occurred in the contralateral hemisphere. These connectomics results showed that both maladaptative and compensation processes coexist in the rat brain following ICH, even at young age and in a disease-free setting. These radiological findings deepen our understanding of ICH-related CI and may serve as biomarkers in the view of future therapeutic intervention.

Dataset Information

Quantitative proteomic analysis of intracerebral hemorrhage in rats with a focus on brain energy metabolism.

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Quantitative proteomic analysis of intracerebral hemorrhage in rats with a focus on brain energy metabolism.

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