Characterization of metabolomics profile changes during development of post-traumatic epilepsy in Rat Brain Tissue (part-III)
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus Norvegicus
TISSUE(S): Brain
DISEASE(S): Epilepsy
PROVIDER: ST001022 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
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| ST001021 | MetabolomicsWorkbench
Project description:Traumatic brain injuries are strongly related to alcohol intoxication as by some estimates half or more of all brain injuries involve at least one intoxicated individual. Additionally, there is mounting evidence that traumatic brain injuries can themselves serve as independent risk factors for the development of alcohol use disorders, particularly when injury occurs during juvenile or adolescent development. Here, we will review the epidemiological and experimental evidence for this phenomenon and discuss potential psychosocial mediators including attenuation of negative affect and impaired decision making as well as neurochemical mediators including disruption in the glutamatergic, GABAergic, and dopaminergic signaling pathways and increases in inflammation.
| S-EPMC5517445 | biostudies-other
Project description:Traumatic brain injury (TBI) in general has varied neuropathological consequences depending upon the intensity and biomechanics of the injury. Furthermore, in pediatric TBI, intrinsic developmental changes add further complexity, necessitating a biochemical dimension for improved TBI characterization. In our earlier study investigating the subacute stage TBI metabolome (72 h post-injury) in a developmental rat model, significant ipsilateral brain biochemical changes occurred across 25 metabolite sets as determined by metabolite set enrichment analysis (MSEA). The broad metabolic perturbation was accompanied by behavioral deficits and neuronal loss across the ipsilateral hemisphere containing the injury epicenter. In order to obtain a consolidated biochemical profile of the TBI assessment, a subgrouping of the 190 identified brain metabolites was performed. Metabolites were divided into seven major subgroups: oxidative energy/mitochondrial, glycolysis/pentose phosphate pathway, fatty acid, amino acid, neurotransmitters/neuromodulators, one-carbon/folate and other metabolites. Subgroups were based on the chemical nature and association with critically altered biochemical pathways after TBI as obtained from our earlier untargeted analysis. Each metabolite subgroup extracted from the ipsilateral sham and TBI brains were modeled using multivariate partial least square discriminant analysis (PLS-DA) with the model accuracy used as a measurable index of TBI neurochemical impact. Volcano plots of each subgroup, corrected for multiple comparisons, determined the TBI neurochemical specificity. The results provide a ranked biochemical profile along with specificity of changes after developmental TBI, enabling a consolidated biochemical template for future classification of different TBI intensities and injury types in animal models.
| S-EPMC6509949 | biostudies-literature
Project description:Epilepsy is a significant but potentially preventable complication of traumatic brain injury (TBI). Previous research in animal models of acquired epilepsy has implicated the calcium-sensitive phosphatase, calcineurin. In addition, our lab recently found that calcineurin activity in the rat hippocampus increases acutely after lateral TBI. Here we use a calcineurin inhibitor test whether an acute increase in calcineurin activity is necessary for the development of late post-traumatic seizures. Adult rats were administered the calcineurin inhibitor Tacrolimus (5mg/kg; i.p.) 1 hour after lateral fluid percussion TBI and then monitored by video-electrocorticography (video-ECoG) for spontaneous seizure activity 5 weeks or 33 weeks later. At 5 weeks post-TBI, we observed epileptiform activity on the video-ECoG of brain injured rats but no seizures. By 33 weeks post-TBI though, nearly all injured rats exhibited spontaneous seizures, including convulsive seizures which were infrequent but lasted minutes (18% of injured rats), and non-convulsive seizures which were frequent but lasted tens of seconds (94% of injured rats). We also identified non-convulsive seizures in a smaller subset of control and sham TBI rats (56%), reminiscent of idiopathic seizures described in other rats strains. Non-convulsive seizures in the brain injured rats, however, were four-times more frequent and two-times longer lasting than in their uninjured littermates. Interestingly, rats administered Tacrolimus acutely after TBI showed significantly fewer non-convulsive seizures than untreated rats, but a similar degree of cortical atrophy. The data thus indicate that administration of Tacrolimus acutely after TBI suppressed non-convulsive seizures months later.
| S-EPMC4287390 | biostudies-literature
Project description:IntroductionPost-traumatic stress disorder (PTSD) is an anxiety disorder induced by psychologically traumatic events. Using a rat model, this study aimed to determine whether psychological trauma alters relative expression between pro-inflammatory and anti-inflammatory markers in microglia. To meet this goal, expression of genes encoding i-NOS, arginase, TNF-α, interleukin-10, CD74, and Mannose Receptor C was analyzed on multiple days following trauma exposure.MethodsSingle-prolonged stress (SPS) was used to model PTSD in male Sprague-Dawley rats. Twenty-four rats (12 Controls and 12 SPS-exposed) were sacrificed on Days 1, 3, and 7 post-SPS. Twenty-four (12 Controls and 12 SPS-exposed) additional rats were exposed to classical fear conditioning on Day 7, and fear extinction on Days 8, 9, 10, 15, 16, and 17. Freezing behavior was measured to assess fear resolution. Microglial isolates were collected from the frontal cortex, and RNA was extracted. Changes in relative expression of target genes were quantified via RT-PCR.ResultsSPS rats showed significant decreases in IL-10 and TNF-α expression and increases in the i-NOS:Arginase and TNF-α:IL-10 ratios compared to Controls on Day 1, but not on Day 3 or Day 7 for any of the dependent variables. Day 17 SPS rats showed a significant decrease in IL-10 expression and an increase in the TNF-α:IL-10 ratio, further characterized by a significant inverse relationship between IL-10 expression and fear persistence.ConclusionPsychological trauma impacts the immunological phenotype of microglia of the frontal cortex. Consequently, future studies should further evaluate the mechanistic role of microglia in PTSD pathology.
| S-EPMC7994680 | biostudies-literature
Project description:Label-free quantitation (LFQ) was applied to proteome profiling of rat brain cortical development during the early postnatal period. Male and female rat brain extracts were prepared using a convenient, detergent-free sample preparation technique at postnatal days (PND) 2, 8, 15, and 22. The PND protein ratios were calculated using Proteome Discoverer, and the PND protein change profiles were constructed separately for male and female animals for key presynaptic, postsynaptic, and adhesion brain proteins. The profiles were compared to the analogous profiles assembled from the published mouse and rat cortex proteomic data, including the fractionated-synaptosome data. The PND protein-change trendlines, Pearson correlation coefficient (PCC), and linear regression analysis of the statistically significant PND protein changes were used in the comparative analysis of the datasets. The analysis identified similarities and differences between the datasets. Importantly, there were significant similarities in the comparison of the rat cortex PND (current work) vs mouse (previously published) PND profiles, although in general, a lower abundance of synaptic proteins in mice than in rats was found. The male and female rat cortex PND profiles were expectedly almost identical (98-99% correlation by PCC), which also substantiated this LFQ nanoflow liquid chromatography-high-resolution mass spectrometry approach.
| S-EPMC10851773 | biostudies-literature
Project description:Agitation is common in the early recovery period following traumatic brain injury (TBI), known as post-traumatic amnesia (PTA). Non-pharmacological interventions are frequently used to manage agitation, yet their efficacy is largely unknown. This systematic review aims to synthesize current evidence on the effectiveness of non-pharmacological interventions for agitation during PTA in adults with TBI. Key databases searched included MEDLINE Ovid SP interface, PubMed, CINAHL, Excerpta Medica Database, PsycINFO and CENTRAL, with additional online reviewing of key journals and clinical trial registries to identify published or unpublished studies up to May 2020. Eligible studies included participants aged 16 years and older, showing agitated behaviours during PTA. Any non-pharmacological interventions for reducing agitation were considered, with any comparator accepted. Eligible studies were critically appraised for methodological quality using Joanna Briggs Institute Critical Appraisal Instruments and findings were reported in narrative form. Twelve studies were included in the review: two randomized cross-over trials, three quasi-experimental studies, four cases series and three case reports. Non-pharmacological interventions were music therapy, behavioural strategies and environmental modifications, physical restraints and electroconvulsive therapy. Key methodological concerns included absence of a control group, a lack of formalised agitation measurement and inconsistent concomitant use of pharmacology. Interventions involving music therapy had the highest level of evidence, although study quality was generally low to moderate. Further research is needed to evaluate non-pharmacological interventions for reducing agitation during PTA after TBI.Systematic review registration number: PROSPERO (CRD42020186802), registered May 2020.
| S-EPMC10148768 | biostudies-literature
Project description:ObjectivesIn the absence of evidence of acute cerebral herniation, normal ventilation is recommended for patients with traumatic brain injury (TBI). Despite this recommendation, ventilation strategies vary during the initial management of patients with TBI and may impact outcome. The goal of this systematic review was to define the best evidence-based practice of ventilation management during the initial resuscitation period.MethodsA literature search of PubMed, CINAHL, and SCOPUS identified studies from 2009 through 2019 addressing the effects of ventilation during the initial post-trauma resuscitation on patient outcomes.ResultsThe initial search yielded 899 articles, from which 13 were relevant and selected for full-text review. Six of the 13 articles met the inclusion criteria, all of which reported on patients with TBI. Either end-tidal carbon dioxide (ETCO2) or partial pressure carbon dioxide (PCO2) were the independent variables associated with mortality. Decreased rates of mortality were reported in patients with normal PCO2 or ETCO2.ConclusionsNormoventilation, as measured by ETCO2 or PCO2, is associated with decreased mortality in patients with TBI. Preventing hyperventilation or hypoventilation in patients with TBI during the early resuscitation phase could improve outcome after TBI.
| S-EPMC8295185 | biostudies-literature
Project description:The aim was to investigate brain network function during working memory (WM) task performance in patients with uncomplicated mild traumatic brain injury (mTBI) in the sub-acute phase post-injury. We were particularly interested in differences between patients with (PCC-present) and without post-concussive complaints (PCC-absent). Fifty-two patients and twenty healthy controls (HCs) (matched for age, sex, education and handedness) were included. Two patient groups were created based on reported post-concussive complaints at two weeks post-injury: PCC-present (n = 32) and PCC-absent (n = 20). Functional MRI scans were made at approximately four weeks post-injury. Participants performed an n-back task consisting of three conditions (0-, 1- and 2-back) with increasing difficulty. General linear model analysis was performed to investigate activation patterns. Independent component analysis was used to identify brain networks. The frontal executive network (FEN), frontoparietal network (FPN) and default mode network (DMN) were selected for further analyses based on their highest task-relatedness. Task accuracy and reaction times were similar for patients with mTBI and HCs. During high WM load (2-vs.0-back contrast), mTBI patients exhibited lower activation within the medial prefrontal cortex compared to HCs. No differences were found between PCC-present and PCC-absent patients. Regarding network function, PCC-absent patients showed stronger deactivation of the DMN compared to PCC-present patients and HCs, especially during difficult task conditions. Furthermore, functional connectivity between the DMN and FEN was lower in PCC-absent patients compared to PCC-present patients. Interestingly, network function did not differ between PCC-present patients and HCs, suggesting that non-injury related factors may underlie post-concussive complaints after mTBI.
| S-EPMC5167217 | biostudies-literature