Inflammation Mediated Epileptogenesis as Possible Mechanism Underlying Ischemic Post-stroke Epilepsy

Tröscher, Anna R.; Gruber, Joachim; Wagner, Johanna; Böhm, Vincent; Wahl, Anna-Sophia; Oertzen, Tim J. von

doi:10.3389/fnagi.2021.781174

Cited by 23 publications

(12 citation statements)

References 128 publications

(222 reference statements)

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“…Although the literature has yet to conclude whether IL-6 is associated with the specific timing of PSE, its proinflammatory role in cerebral ischemia suggests its ability to be a marker for the development of seizures. It is assumed that central and peripheral inflammation secondary to early or late stroke damages the integrity of the blood-brain barrier [ 1 , 36 ]. Chronic inflammation also impairs neuronal plasticity by affecting transcription mechanisms that result in aberrant and epileptogenic circuits.…”

Section: Review Outlinementioning

confidence: 99%

Poststroke Seizure and Epilepsy: A Review of Incidence, Risk Factors, Diagnosis, Pathophysiology, and Pharmacological Therapies

Phan

Ramos

Soares

et al. 2022

Oxidative Medicine and Cellular Longevity

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Stroke is the most common cause of epilepsy and ultimately leads to a decrease in the quality of life of those affected. Ischemic and hemorrhagic strokes can both lead to poststroke epilepsy (PSE). Significant risk factors for PSE include age < 65 age less than 65 years, stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), cortical involvement, and genetic factors such as TRPM6 polymorphism. The diagnosis of PSE is made by using imaging modalities, blood biomarkers, and prognostic criteria. Electroencephalography (EEG) is currently the gold standard to diagnose PSE, while new combinations of modalities are being tested to increase diagnostic specificity. This literature review uncovers a newly found mechanism for the pathology of poststroke epilepsy. The pathogenesis of early-onset and late-onset is characterized by sequelae of neuronal cellular hypoxia and disruption of the blood-brain barrier, respectively. Interleukin-6 is responsible for increasing the activity of glial cells, causing gliosis and hyperexcitability of neurons. Epinephrine, high-mobility group protein B1, downregulation of CD32, and upregulation of HLA-DR impact the pathology of poststroke epilepsy by inhibiting the normal neuronal immune response. Decreased levels of neuropeptide Y, a neurotransmitter, act through multiple unique mechanisms, such as inhibiting intracellular Ca2+ accumulation and acting as an anti-inflammatory, also implemented in the worsening progression of poststroke epilepsy. Additionally, CA1 hippocampal resonant neurons that increase theta oscillation are associated with poststroke epilepsy. Hypertensive small vessel disease may also have an implication in the temporal lobe epilepsy by causing occult microinfarctions. Furthermore, this review highlights the potential use of statins as primary prophylaxis against PSE, with multiple studies demonstrating a reduction in incidence using statins alone, statins in combination with antiepileptic drugs (AEDs), and statins with aspirin. The evidence strongly suggests that the second generation AEDs are a superior treatment method for PSE. Data from numerous studies demonstrate their relative lack of significant drug interactions, increased tolerability, and potential superiority in maintaining seizure-free status.

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Section: Review Outlinementioning

confidence: 99%

Poststroke Seizure and Epilepsy: A Review of Incidence, Risk Factors, Diagnosis, Pathophysiology, and Pharmacological Therapies

Phan

Ramos

Soares

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…According to [20], little is known about the underlying pathological mechanisms in patients affected by postischemic epileptogenesis, resulting in the development of chronic seizures. However, the author highlights the hypothesis that persistent neuroinflammation and glial scar formation cause aberrant neuronal firing.…”

Section: Neurogenesis Neural Reorganization and Aberrant Sproutingmentioning

confidence: 99%

Pharmacological perspectives and mechanisms involved in epileptogenesis

Marques

Kawamura

Quintanilha

et al. 2022

Beni-Suef Univ J Basic Appl Sci

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Background Epileptogenesis can be defined as the process by which a previously healthy brain develops a tendency toward recurrent electrical activity, occurring in three phases: first as an initial trigger (such as stroke, infections, and traumatic brain injury); followed by the latency period and the onset of spontaneous and recurrent seizures which characterizes epilepsy. Main body The mechanisms that may be involved in epileptogenesis are inflammation, neurogenesis, migration of neurons to different regions of the brain, neural reorganization, and neuroplasticity.In recent years, experimental studies have enabled the discovery of several mechanisms involved in the process of epileptogenesis, mainly neuroinflammation, that involves the activation of glial cells and an increase in specific inflammatory mediators. The lack of an experimental animal model protocol for epileptogenic compounds contributes to the difficulty in understanding disease development and the creation of new drugs. Conclusion To solve these difficulties, a new approach is needed in the development of new AEDs that focus on the process of epileptogenesis and the consolidation of animal models for studies of antiepileptogenic compounds, aiming to reach the clinical phases of the study. Some examples of these compounds are rapamycin, which inhibits mTOR signaling, and losartan, that potentiates the antiepileptogenic effect of some AEDs. Based on this, this review discusses the main mechanisms involved in epileptogenesis, as well as its pharmacological approach.

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“…( Eltzschig and Eckle, 2011 ; Chen et al, 2019 ). More recently, emerging evidence suggests that H/I inflammation, a quick pathological response to oxygen/blood flow depletion, has a major impact on H/I injury through pro-inflammatory cytokines and their signaling pathways ( Chen et al, 2020c ; Sikora et al, 2021 ; Troscher et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…Different organs may suffer from H/I inflammation in different ways, thus leading to various H/I-related diseases. H/I neuroinflammation induces brain injury in ischemic stroke and post-stroke epilepsy ( Li X. et al, 2020 ; Troscher et al, 2021 ; Xue Y. et al, 2021 ), while H/I inflammation leads to other pathophysiological events in peripheral organs, including heart failure, acute kidney injury, and hepatocellular damages ( Nangaku and Eckardt, 2007 ; Klune and Tsung, 2010 ; Frohlich et al, 2013 ; Yang et al, 2015 ). On the other side, some beneficial reaction may go through the regulation of inflammatory events.…”

Section: Introductionmentioning

confidence: 99%

Hypoxic/Ischemic Inflammation, MicroRNAs and δ-Opioid Receptors: Hypoxia/Ischemia-Sensitive Versus-Insensitive Organs

Chen

Zhao

et al. 2022

Front. Aging Neurosci.

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Hypoxia and ischemia cause inflammatory injury and critically participate in the pathogenesis of various diseases in various organs. However, the protective strategies against hypoxic and ischemic insults are very limited in clinical settings up to date. It is of utmost importance to improve our understanding of hypoxic/ischemic (H/I) inflammation and find novel therapies for better prevention/treatment of H/I injury. Recent studies provide strong evidence that the expression of microRNAs (miRNAs), which regulate gene expression and affect H/I inflammation through post-transcriptional mechanisms, are differentially altered in response to H/I stress, while δ-opioid receptors (DOR) play a protective role against H/I insults in different organs, including both H/I-sensitive organs (e.g., brain, kidney, and heart) and H/I-insensitive organs (e.g., liver and muscle). Indeed, many studies have demonstrated the crucial role of the DOR-mediated cyto-protection against H/I injury by several molecular pathways, including NLRP3 inflammasome modulated by miRNAs. In this review, we summarize our recent studies along with those of others worldwide, and compare the effects of DOR on H/I expression of miRNAs in H/I-sensitive and -insensitive organs. The alternation in miRNA expression profiles upon DOR activation and the potential impact on inflammatory injury in different organs under normoxic and hypoxic conditions are discussed at molecular and cellular levels. More in-depth investigations into this field may provide novel clues for new protective strategies against H/I inflammation in different types of organs.

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Inflammation Mediated Epileptogenesis as Possible Mechanism Underlying Ischemic Post-stroke Epilepsy

Cited by 23 publications

References 128 publications

Poststroke Seizure and Epilepsy: A Review of Incidence, Risk Factors, Diagnosis, Pathophysiology, and Pharmacological Therapies

Poststroke Seizure and Epilepsy: A Review of Incidence, Risk Factors, Diagnosis, Pathophysiology, and Pharmacological Therapies

Pharmacological perspectives and mechanisms involved in epileptogenesis

Hypoxic/Ischemic Inflammation, MicroRNAs and δ-Opioid Receptors: Hypoxia/Ischemia-Sensitive Versus-Insensitive Organs

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