Maladaptive upregulation of aminoprocalcitonin fuels seizure self-sustaining by boosting energy supply in refractory status epilepticus
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE217955 | GEO | 2023/05/10
REPOSITORIES: GEO
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Project description:Maladaptive upregulation of aminoprocalcitonin fuels seizure self-sustaining by boosting energy supply in refractory status epilepticus
| PRJNA901466 | ENA
Project description:Epilepsy is a common neurological disorder which affects patients physically and mentally and causes a real burden for the patient, family and society both medically and economically. Currently, more than one-third of epilepsy patients are still under unsatisfied control, even with new anticonvulsants. Other measures may be added to those with drug-resistant epilepsy. Excessive neuronal synchronization is the hallmark of epileptic activity and prolonged epileptic discharges such as in status epilepticus can lead to various cellular events and result in neuronal damage or death. Unbalanced oxidative status is one of the early cellular events and a critical factor to determine the fate of neurons in epilepsy. To counteract excessive oxidative damage through exogenous antioxidant supplements or induction of endogenous antioxidative capability may be a reasonable approach for current anticonvulsant therapy. In this article, we will introduce the critical roles of oxidative stress and further discuss the potential use of antioxidants in this devastating disease.
| S-EPMC7690410 | biostudies-literature
Project description:Phagocytosis requires locally coordinated cytoskeletal rearrangements driven by actin polymerization and myosin motor activity. How this actomyosin dynamics is dependent upon systems that provide access to ATP at phagosome microdomains has not been determined. We analyzed the role of brain-type creatine kinase (CK-B), an enzyme involved in high-energy phosphoryl transfer. We demonstrate that endogenous CK-B in macrophages is mobilized from the cytosolic pool and coaccumulates with F-actin at nascent phagosomes. Live cell imaging with XFP-tagged CK-B and beta-actin revealed the transient and specific nature of this partitioning process. Overexpression of a catalytic dead CK-B or CK-specific cyclocreatine inhibition caused a significant reduction of actin accumulation in the phagocytic cup area, and reduced complement receptor-mediated, but not Fc-gammaR-mediated, ingestion capacity of macrophages. Finally, we found that inhibition of CK-B affected phagocytosis already at the stage of particle adhesion, most likely via effects on actin polymerization behavior. We propose that CK-B activity in macrophages contributes to complement-induced F-actin assembly events in early phagocytosis by providing local ATP supply.
| S-EPMC2265766 | biostudies-literature
Project description:Status Epilepticus (SE) is induced in mice (C57Bl/6J) through electrical stimulation (90min, 100 ms trains of 1 ms, 2 trains per 1 s, 250 μA peak current intensity). RNA was extracted from the hippocampi at 24 h and 28 d after induction. In wild-type RNA was extracted on the 22nd day. microRNA expressions were measured via microarray technology using Exiqon's miCURY™ LNA Arrays. 3 conditions, SSSE mouse model at 24 h and 28 d, and a control group, each of 8 replicates.
2014-01-01 | E-GEOD-51842 | biostudies-arrayexpress
Project description:Status Epilepticus (SE) is induced in mice (C57Bl/6J) through electrical stimulation (90min, 100 ms trains of 1 ms, 2 trains per 1 s, 250 μA peak current intensity). RNA was extracted from the hippocampi at 24 h and 28 d after induction. In wild-type RNA was extracted on the 22nd day. microRNA expressions were measured via microarray technology using Exiqon's miCURY™ LNA Arrays.
2014-01-01 | GSE51842 | GEO
Project description:Biomarkers of neuronal damage in status epilepticus (SE) would be of great relevance for clinical and research purposes. In a retrospective cross-sectional study, serum neurofilament light chain (NfL) levels were measured in patients with SE (30 subjects), patients with drug-resistant epilepsy (30 subjects), and healthy controls (30 subjects). Serum NfL levels were higher in patients with SE (median = 26.15 pg/ml) compared to both epilepsy patients (median = 7.35 pg/ml) and healthy controls (median = 6.81 pg/ml; p < .001). In patients with SE, serum NfL levels showed a high correlation with cerebrospinal fluid (CSF) NfL (τ = .68, p < .001) as well as with CSF total tau (t-tau) levels (τ = .627, p < .001); they were higher in SE lasting >24 h (p = .013), in refractory/superrefractory SE (p = .004), and in patients who died within 30 days or who presented a worsening of clinical conditions (p = .001). Values of >28.8 pg/ml predicted 30-day clinical worsening or death (odds ratio [OR] = 10.83, 95% confidence interval [CI] = 1.96-59.83, p = .006) and SE refractoriness (OR = 9.33, 95% CI = 1.51-57.65, p = .016). In conclusion, serum NfL levels are increased in SE and correlate with SE treatment response, duration, and outcomes, therefore representing a promising biomarker of seizure-related neuronal damage.
| S-EPMC9299158 | biostudies-literature
Project description:ObjectivesDelayed management of nonconvulsive status epilepticus (NCSE) can lead to an increased morbidity and mortality. We previously established that inefficient treatment of NCSE at our institution stemmed from delayed initiation of emergent anti-seizure medications (ASM). In the present study, we assessed the trajectories of these time parameters and determined patient outcomes following the specific quality improvement (QI) interventions.MethodsThe QI interventions, including the revision of the educational content for trainees and pharmacy workflow optimization were implemented between January 2019 and September 2021 by a dedicated multidisciplinary task force. The times needed to initiate and administer the ASMs for patients with NCSE as well as patient mortality were assessed in comatose and noncomatose patients and compared with the corresponding values prior to the interventions.ResultsThere were 79 occurrences of NCSE in 74 patients. The median time from seizure detection on EEG to the order of the first and second ASM for NCSE was reduced by 4 (p = 0.83) and 8 min (p = 0.52), respectively compared to the times prior to the initiation of interventions. The median times from the order to administration of the first and third ASM for all NCSE occurrences were reduced by 8 and 10 min, respectively (p = 0.28 and p = 0.10). In the present cohort of comatose patients, the median time spent to order the first ASM was reduced by 16.5 min and the time to administer it reduced by 35 min compared to that in our previous study. The overall patient mortality was decreased by 11.1%.SignificanceMore efficient delivery of rescue ASMs in patients with NCSE and improvement in their mortality can be achieved with multidisciplinary team efforts aimed at streamlining the functioning of pharmacy and strengthening the education of trainees and nurses.
| S-EPMC9979156 | biostudies-literature
Project description:The Genetic Audiogenic Seizure Hamster from Salamanca (GASH/Sal), an animal model of reflex epilepsy, exhibits generalized tonic-clonic seizures in response to loud sound with the epileptogenic focus localized in the inferior colliculus (IC). Ictal events in seizure-prone strains cause gene deregulation in the epileptogenic focus, which can provide insights into the epileptogenic mechanisms. Thus, the present study aimed to determine the expression profile of key genes in the IC of the GASH/Sal after the status epilepticus. For such purpose, we used RNA-Seq to perform a comparative study between the IC transcriptome of GASH/Sal and that of control hamsters both subjected to loud sound stimulation. After filtering for normalization and gene selection, a total of 36 genes were declared differentially expressed from the RNA-seq analysis in the IC. A set of differentially expressed genes were validated by RT-qPCR showing significant differentially expression between GASH/Sal hamsters and Syrian control hamsters. The confirmed differentially expressed genes were classified on ontological categories associated with epileptogenic events similar to those produced by generalized tonic seizures in humans. Subsequently, based on the result of metabolomics, we found the interleukin-4 and 13-signaling, and nucleoside transport as presumably altered routes in the GASH/Sal model. This research suggests that seizures in GASH/Sal hamsters are generated by multiple molecular substrates, which activate biological processes, molecular processes, cellular components and metabolic pathways associated with epileptogenic events similar to those produced by tonic seizures in humans. Therefore, our study supports the use of the GASH/Sal as a valuable animal model for epilepsy research, toward establishing correlations with human epilepsy and searching new biomarkers of epileptogenesis.
| S-EPMC7264424 | biostudies-literature
Project description:ObjectiveThe goal of this research was to evaluate the effect of DM type 2 (DM2) on SE severity, neurodegeneration, and brain oxidative stress (OS) secondary to seizures.MethodsDM2 was induced in postnatal day (P) 3 male rat pups by injecting streptozocin (STZ) 100 mg/kg; control rats were injected with citrate buffer as vehicle. At P90, SE was induced by the lithium-pilocarpine administration and seizure latency, frequency, and severity were evaluated. Neurodegeneration was assessed 24 h after SE by Fluoro-Jade B (F-JB) staining, whereas OS was estimated by measuring lipid peroxidation and reactive oxygen species (ROS).ResultsDM2 rats showed an increase in latency to the first generalized seizure and SE onset, had a higher number and a longer duration of seizures, and displayed a larger neurodegeneration in the hippocampus (CA3, CA1, dentate gyrus, and hilus), the piriform cortex, the dorsomedial nucleus of the thalamus and the cortical amygdala. Our results also show that only SE, neither DM2 nor the combination of DM2 with SE, caused the increase in ROS and brain lipid peroxidation.SignificanceDM2 causes higher seizure severity and neurodegeneration but did not exacerbate SE-induced OS under these conditions.Plain language summaryOur research performed in animal models suggests that type 2 diabetes mellitus (DM2) may be a risk factor for causing higher seizure severity and seizure-induced neuron cell death. However, even when long-term seizures promote an imbalance between brain pro-oxidants and antioxidants, DM2 does not exacerbate that disproportion.
| S-EPMC10984310 | biostudies-literature