Status Epilepticus

Seinfeld, Syndi; Goodkin, Howard P.; Shinnar, Shlomo

doi:10.1101/cshperspect.a022830

Cited by 54 publications

(38 citation statements)

References 105 publications

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“…tatus epilepticus (SE) is a grave medical crisis that requires swift remedy through all age groups (1,2). It can produce substantial neurodegeneration, blood-brain barrier disruption, and inflammation in the hippocampus if not extinguished quickly by antiepileptic drug (AED) treatment (3)(4)(5).…”

mentioning

confidence: 99%

Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus

Long

Upadhya

Hattiangady

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

332

299

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Status epilepticus (SE), a medical emergency that is typically terminated through antiepileptic drug treatment, leads to hippocampus dysfunction typified by neurodegeneration, inflammation, altered neurogenesis, as well as cognitive and memory deficits. Here, we examined the effects of intranasal (IN) administration of extracellular vesicles (EVs) secreted from human bone marrowderived mesenchymal stem cells (MSCs) on SE-induced adverse changes. The EVs used in this study are referred to as A1-exosomes because of their robust antiinflammatory properties. We subjected young mice to pilocarpine-induced SE for 2 h and then administered A1-exosomes or vehicle IN twice over 24 h. The A1-exosomes reached the hippocampus within 6 h of administration, and animals receiving them exhibited diminished loss of glutamatergic and GABAergic neurons and greatly reduced inflammation in the hippocampus. Moreover, the neuroprotective and antiinflammatory effects of A1-exosomes were coupled with long-term preservation of normal hippocampal neurogenesis and cognitive and memory function, in contrast to waned and abnormal neurogenesis, persistent inflammation, and functional deficits in animals receiving vehicle. These results provide evidence that IN administration of A1-exosomes is efficient for minimizing the adverse effects of SE in the hippocampus and preventing SE-induced cognitive and memory impairments.status epilepticus | memory dysfunction | neuroinflammation | exosomes | adult neurogenesis S tatus epilepticus (SE) is a grave medical crisis that requires swift remedy through all age groups (1, 2). It can produce substantial neurodegeneration, blood-brain barrier disruption, and inflammation in the hippocampus if not extinguished quickly by antiepileptic drug (AED) treatment (3-5). An episode of extended SE is sufficient to cause chronic hippocampus dysfunction, exemplified by persistent inflammation with activation of microglia and monocyte infiltration, loss of sizable fractions of several subclasses of inhibitory interneurons, aberrant and waned neurogenesis, hippocampus-dependent cognitive and memory impairments, and chronic epilepsy (5-12). Numerous situations such as head trauma, stroke, Alzheimer's disease, brain tumor, and encephalitis can engender SE. Although administration of AEDs leads to termination of SE in most instances, it does not thwart the evolution of SE into chronic epilepsy (13-16). A multitude of changes ensue in the hippocampus after an episode of SE, which evolve over a period of months, years, or even decades, and result in chronic epilepsy when they have reached certain thresholds (11,17,18). Hence, there is an urgent need to find an adjuvant therapy with AEDs that not only provides neuroprotection and suppression of inflammation in the early phase after SE but also maintains normal neurogenesis, preserves cognitive and memory function, and thwarts epilepsy development in the chronic phase after SE. The i.v. administration of bone marrow-derived mononuclear cells (MNCs) or mesenchymal stem cells (...

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mentioning

confidence: 99%

Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus

Long

Upadhya

Hattiangady

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

332

299

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“…Clinical studies have demonstrated that SE patients present neurological deficits associated with seizures that correspond to imaging changes, such as high T2WI signals, and brain atrophy [20]. The existence of pathological changes of hippocampus, limbic system, cortex and cerebellar tissue have been confirmed by studies in both animal models and SE patients [21,22]. SE can induce increased oxygen consumption, apnea, and vasomotor dysfunction, which lead to cerebral hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Thymoquinone attenuates brain injury via an antioxidative pathway in a status epilepticus rat model

Shao

Huang

et al. 2017

Translational Neuroscience

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Status epilepticus (SE) is a common, lifethreatening neurologic disorder characterized by acute, prolonged epileptic seizures. The incidence rate of SE is about 0.05 to 0.1% in the general population and 1.1 to 14% in the epileptic population. SE has a poor prognosis because seizures that cannot be terminated quickly result in irreversible brain injury. It is known that multiple factors are involved in the pathogenesis of brain injury induced by SE, one of which is oxidative stress [1][2]. The generation of excess free radicals and increase in lipid peroxidation that occur during SE damage brain tissue, therefore, antioxidants might be effective for treatment of SE [3][4][5].Thymoquinone (TQ), a bioactive monomer derived from black seed (Nigella sativa) oil, has significant antioxidant effects [6][7][8]. It has been shown to suppress oxidative stress and attenuate seizure activity and lower hippocampal neuronal loss in an epilepsy model and in children with refractory seizures [9][10][11]. We speculate that TQ alleviates the brain injury of SE by modulating oxidative stress. It is thought that the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a key defensive role against oxidative stress in epilepsy [12][13][14]. This study evaluated the protective effects of TQ on brain injury in a status epilepticus rat model, and the underlying mechanism related to antioxidative pathway using biochemistry techniques and behavioral and electrophysiological tests. Materials and methods THYMOQUINONE ATTENUATES BRAIN INJURY VIA AN ANTI-OXIDATIVE PATHWAY IN A STATUS EPILEPTICUS RAT MODEL AbstractAim: Status epilepticus (SE) results in the generation of reactive oxygen species (ROS), which contribute to seizure-induced brain injury. It is well known that oxidative stress plays a pivotal role in status epilepticus (SE). Thymoquinone (TQ) is a bioactive monomer extracted from black cumin (Nigella sativa) seed oil that has anti-inflammatory, anti-cancer, and antioxidant activity in various diseases. This study evaluated the protective effects of TQ on brain injury in a lithium-pilocarpine rat model of SE and investigated the underlying mechanism related to antioxidative pathway. Methods: Electroencephalogram and Racine scale were used to value seizure severity. Passive-avoidance test was used to determine learning and memory function. Moreover, anti-oxidative activity of TQ was observed using Western blot and super oxide dismutase (SOD) activity assay. Results: Latency to SE increased in the TQ-pretreated group compared with rats in the model group, while the total power was significantly lower. Seizure severity measured on the Racine scale was significantly lower in the TQ group compared with the model group. Results of behavioral experiments suggest that TQ may also have a protective effect on learning and memory function. Investigation of the protective mechanism of TQ showed that TQ-pretreatment significantly increased the expression of Nrf2, HO-1 proteins and SOD in the hippocampus. Conclusion: these findings...

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“…Recent clinical and basic studies have highlighted the negative impact of SE in the young on brain and behavior, including epileptogenesis, long‐term changes in brain imaging, as well as cognitive function . Although some controversies remain, basic and clinical studies have converged Basic studies have shown that the mechanisms of seizure induction, and maintenance, can change both over developmental time and during individual seizures.…”

Section: Pathophysiology Of Sementioning

confidence: 99%

Treatment of early life status epilepticus: What can we learn from animal models?

2018

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SummaryTreatment of status epilepticus (SE) in infants and children is challenging. There is a recognition that a broad set of developmental processes need to be considered to fully appreciate the physiologic complexity of severe seizures, and seizure outcomes, in infants and children. The development and use of basic models to elucidate important mechanisms will help further our understanding of these processes. Here we review some of the key experimental models and consider several areas relevant to treatment that could lead to productive translational research. Terminating seizures quickly is essential. Understanding pharmacoresistance of SE as it relates to receptor trafficking will be critical to seizure termination. Once a severe seizure is terminated, how will the developing brain respond? Basic studies suggest that there are important acute and long‐term histopathologic, and pathophysiologic, consequences that, if left unaddressed, will produce long‐lasting deficits on the form and function of the central nervous system. To fully utilize the evidence that basic models produce, age‐ and development‐ and model‐specific frameworks have to be considered carefully. Studies have demonstrated that severe seizures can cause perturbations to developmental processes during critical periods of development that lead to life‐long deficits. Unfortunately, some of the drugs that are commonly used to treat seizures may also produce negative outcomes by enhancing Cl‐‐mediated depolarization, or by accelerating programmed cell death. More research is needed to understand these phenomena and their relevance to the human condition, and to develop rational drugs that protect the developing brain from severe seizures to the fullest extent possible.

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Status Epilepticus

Cited by 54 publications

References 105 publications

Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus

Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus

Thymoquinone attenuates brain injury via an antioxidative pathway in a status epilepticus rat model

Treatment of early life status epilepticus: What can we learn from animal models?

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