Dataset Information

Celecoxib treatment alleviates cerebral injury in a rat model of post-traumatic epilepsy.

ABSTRACT:

Background

An important factor contributing to the development and occurrence of post-traumatic epilepsy (PTE) is neuroinflammation and oxidative stress. The effects of celecoxib include inhibiting inflammatory reactions and antioxidant stress and reducing seizures, making it a potential epilepsy treatment solution.

Objective

To observe the effect of celecoxib on early epilepsy in post-traumatic epilepsy rats. Methods: Twenty-four adult healthy male Sprague-Dawley rats were randomly assigned to three groups: sham-operated, PTE, and celecoxib. A rat model of PTE was established by injecting ferrous chloride into the right frontal cortex. Afterward, the behavior of rats was observed and recorded. 3.0T superconducting magnetic resonance imaging (MRI) was used to describe the changes in ADC values of the brain. HE and Nissl staining were also used to detect the damage to frontal lobe neurons. Furthermore, the expression of COX-2 protein in the right frontal lobe was detected by Western blot. Moreover, the contents of IL-1 and TNF-α in the right frontal lobe were detected by enzyme-linked immunosorbent assay.

Results

Compared with the PTE group, the degree of seizures in rats treated with celecoxib declined dramatically (P < 0.05). Celecoxib-treated rats had significant decreases in tissue structural damage and cell death in the brain. The results of the MRI showed that celecoxib reduced the peripheral edema zone and ADC value of the cortex around the damaged area of the right frontal lobe in the celecoxib-treatment group, which was significantly decreased compared with the PTE group (P < 0.05). Furthermore, celecoxib decreased the expression of COX-2, IL-1β, and TNF-α in brain tissue (P < 0.05).

Conclusions

In PTE rats, celecoxib significantly reduced brain damage and effectively reduced seizures. As a result of celecoxib's ability to inhibit inflammation, it can reduce the edema caused by injury in rat brain tissue.

SUBMITTER: Chen L

PROVIDER: S-EPMC10710164 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Celecoxib treatment alleviates cerebral injury in a rat model of post-traumatic epilepsy.

Chen Lei L Niu Qingsheng Q Gao Caibin C Du Fang F

PeerJ 20231206

<h4>Background</h4>An important factor contributing to the development and occurrence of post-traumatic epilepsy (PTE) is neuroinflammation and oxidative stress. The effects of celecoxib include inhibiting inflammatory reactions and antioxidant stress and reducing seizures, making it a potential epilepsy treatment solution.<h4>Objective</h4>To observe the effect of celecoxib on early epilepsy in post-traumatic epilepsy rats. Methods: Twenty-four adult healthy male Sprague-Dawley rats were random ...[more]

PMID: 38077432

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Project description:BackgroundTraumatic brain injury (TBI) initiates a complex sequence of destructive and neuroprotective cellular responses. The initial mechanical injury is followed by an extended time period of secondary brain damage. Due to the complicated pathological picture a better understanding of the molecular events occurring during this secondary phase of injury is needed. This study was aimed at analysing gene expression patterns following cerebral cortical contusion in rat using high throughput microarray technology with the goal of identifying genes involved in an early and in a more delayed phase of trauma, as genomic responses behind secondary mechanisms likely are time-dependent.ResultsAmong the upregulated genes 1 day post injury, were transcription factors and genes involved in metabolism, e.g. STAT-3, C/EBP-delta and cytochrome p450. At 4 days post injury we observed increased gene expression of inflammatory factors, proteases and their inhibitors, like cathepsins, alpha-2-macroglobulin and C1q. Notably, genes with biological function clustered to immune response were significantly upregulated 4 days after injury, which was not found following 1 day. Osteopontin and one of its receptors, CD-44, were both upregulated showing a local mRNA- and immunoreactivity pattern in and around the injury site. Fewer genes had decreased expression both 1 and 4 days post injury and included genes implicated in transport, metabolism, signalling, and extra cellular matrix formation, e.g. vitronectin, neuroserpin and angiotensinogen.ConclusionThe different patterns of gene expression, with little overlap in genes, 1 and 4 days post injury showed time dependence in genomic responses to trauma. An early induction of factors involved in transcription could lead to the later inflammatory response with strongly upregulated CD-44 and osteopontin expression. An increased knowledge of genes regulating the pathological mechanisms in trauma will help to find future treatment targets. Since trauma is a risk factor for development of neurodegenerative disease, this knowledge may also reduce late negative effects.

Project description:ObjectiveThe development of post-traumatic epilepsy (PTE) following traumatic brain injury (TBI) is associated with unfavorable functional outcomes, and the global function of PTE patients might change dynamically overtime. Predicting the long-term functional outcomes of patients with PTE may help to develop accurate rehabilitation programs and improve their quality of life. Based on this, the objective of this study is to use clinical data to derive and validate a model for predicting the functional outcomes of patients with PTE after moderate-to-severe TBI.MethodsThis study retrospectively analyzed 721 patients with PTE after moderate-to-severe TBI in the Epilepsy Centre, Beijing Tiantan Hospital, from January 2013 to December 2018. All patients had favorable global function as indicated by the Glasgow Outcome Scale-Extended (GOSE) at the time of their first late post-traumatic seizure (PTS) onset, and the 5-year global function after the first late PTS onset was chosen as the principal outcome of interest. To identify possible predictors for the global functional outcomes, univariate and multivariate logistic regression techniques were used. A prognostic model was established using these identified predictors, the internal validation with the bootstrapping method was performed, and the model was then visualized as a graphical score chart.ResultsThe 5-year global functional outcome of 98 (13.59%) patients was unfavorable, and the temporal lobe lesion was found as the strongest predictor of unfavorable outcomes. The final prognostic model also included the following other predictors: gender, age at TBI, multiple injuries, the severity of TBI, and latency of PTE. Discrimination was satisfactory with C-statistic of 0.754 (0.707 - 0.800), the goodness-of-fit test indicated good calibration (P = 0.137), and the C-statistic was 0.726 for internal validation. A graphical score chart was also constructed to provide the probability of an unfavorable 5-year global functional outcomes more readily.ConclusionsClearer treatment strategies are essential to help ameliorate the global functional outcomes of patients with PTE. Our proposed prognostic model has significant potential to be used in the clinic for predicting global functional outcomes among patients with PTE after moderate-to-severe TBI.

Project description:Brain atrophy induced by traumatic brain injury (TBI) progresses in parallel with epileptogenesis over time, and thus accurate placement of intracerebral electrodes to monitor seizure initiation and spread at the chronic postinjury phase is challenging. We evaluated in adult male Sprague Dawley rats whether adjusting atlas-based electrode coordinates on the basis of magnetic resonance imaging (MRI) increases electrode placement accuracy and the effect of chronic electrode implantations on TBI-induced brain atrophy. One group of rats (EEG cohort) was implanted with two intracortical (anterior and posterior) and a hippocampal electrode right after TBI to target coordinates calculated using a rat brain atlas. Another group (MRI cohort) was implanted with the same electrodes, but using T2-weighted MRI to adjust the planned atlas-based 3D coordinates of each electrode. Histological analysis revealed that the anterior cortical electrode was in the cortex in 83% (25% in targeted layer V) of the EEG cohort and 76% (31%) of the MRI cohort. The posterior cortical electrode was in the cortex in 40% of the EEG cohort and 60% of the MRI cohort. Without MRI-guided adjustment of electrode tip coordinates, 58% of the posterior cortical electrodes in the MRI cohort will be in the lesion cavity, as revealed by simulated electrode placement on histological images. The hippocampal electrode was accurately placed in 82% of the EEG cohort and 86% of the MRI cohort. Misplacement of intracortical electrodes related to their rostral shift due to TBI-induced cortical and hippocampal atrophy and caudal retraction of the brain, and was more severe ipsilaterally than contralaterally (p < 0.001). Total lesion area in cortical subfields targeted by the electrodes (primary somatosensory cortex, visual cortex) was similar between cohorts (p > 0.05). MRI-guided adjustment of coordinates for electrodes improved the success rate of intracortical electrode tip placement nearly to that at the acute postinjury phase (68% vs. 62%), particularly in the posterior brain, which exhibited the most severe postinjury atrophy. Overall, MRI-guided electrode implantation improved the quality and interpretation of the origin of EEG-recorded signals.

Project description:ObjectiveAlthough traumatic brain injury (TBI) and post-traumatic epilepsy (PTE) are common, there are no prospective models quantifying individual epilepsy risk after moderate-to-severe TBI (msTBI). We generated parsimonious prediction models to quantify individual epilepsy risk between acute inpatient rehabilitation for individuals 2 years after msTBI.MethodsWe used data from 6089 prospectively enrolled participants (≥16 years) in the TBI Model Systems National Database. Of these, 4126 individuals had complete seizure data collected over a 2-year period post-injury. We performed a case-complete analysis to generate multiple prediction models using least absolute shrinkage and selection operator logistic regression. Baseline predictors were used to assess 2-year seizure risk (Model 1). Then a 2-year seizure risk was assessed excluding the acute care variables (Model 2). In addition, we generated prognostic models predicting new/recurrent seizures during Year 2 post-msTBI (Model 3) and predicting new seizures only during Year 2 (Model 4). We assessed model sensitivity when keeping specificity ≥.60, area under the receiver-operating characteristic curve (AUROC), and AUROC model performance through 5-fold cross-validation (CV).ResultsModel 1 (73.8% men, 44.1 ± 19.7 years, 76.1% moderate TBI) had a model sensitivity = 76.00% and average AUROC = .73 ± .02 in 5-fold CV. Model 2 had a model sensitivity = 72.16% and average AUROC = .70 ± .02 in 5-fold CV. Model 3 had a sensitivity = 86.63% and average AUROC = .84 ± .03 in 5-fold CV. Model 4 had a sensitivity = 73.68% and average AUROC = .67 ± .03 in 5-fold CV. Cranial surgeries, acute care seizures, intracranial fragments, and traumatic hemorrhages were consistent predictors across all models. Demographic and mental health variables contributed to some models. Simulated, clinical examples model individual PTE predictions.SignificanceUsing information available, acute-care, and year-1 post-injury data, parsimonious quantitative epilepsy prediction models following msTBI may facilitate timely evidence-based PTE prognostication within a 2-year period. We developed interactive web-based tools for testing prediction model external validity among independent cohorts. Individualized PTE risk may inform clinical trial development/design and clinical decision support tools for this population.

Project description:IntroductionPost-traumatic epilepsy (PTE) is a recognised complication of traumatic brain injury (TBI), and is associated with higher rates of mortality and morbidity when compared with patients with TBI who do not develop PTE. The majority of the literature on PTE has focused on adult populations, and consequently there is a paucity of information regarding paediatric cohorts. Additionally, there is considerable heterogeneity surrounding the reported incidence of PTE following childhood TBI in the current literature. The primary aim of our study is to summarise reported PTE incidences in paediatric populations to derive an accurate estimate of the global incidence of PTE following childhood TBI. Our secondary aim is to explore risk factors that increase the likelihood of developing PTE.Methods and analysisA systematic literature search of Embase (1947-2021), PubMed (1996-2021) and Web of Science (1900-2021) will be conducted. Publications in English that report the incidence of PTE in populations under 18 years of age will be included. Publications that evaluate fewer than 10 patients, report an alternative cause of epilepsy, or in which a paediatric cohort is not discernable, will be excluded. Independent investigators will identify the relevant publications, and discrepancies will be adjudicated by a third independent investigator. Data extracted will include incidence of PTE, time intervals between TBI and PTE, seizure characteristics, injury characteristics, patient demographics and clinical data. Data extraction will be performed by two independent investigators and cross-checked by a third investigator. A descriptive analysis of PTE incidence will be conducted and a weighted mean will be calculated. If sufficient data are available, stratified meta-analysis of subgroups will also be conducted.Ethics and disseminationEthics approval was not required for this study. We intend to publish our findings in a high-quality peer-reviewed journal on completion.Prospero registration numberCRD42021245802.

Dataset Information

Celecoxib treatment alleviates cerebral injury in a rat model of post-traumatic epilepsy.

Background

Objective

Results

Conclusions

Publications

Celecoxib treatment alleviates cerebral injury in a rat model of post-traumatic epilepsy.

Similar Datasets

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