Dexamethasone after early-life seizures attenuates increased susceptibility to seizures, seizure-induced microglia activation and neuronal injury later in life

Fox, Patrick; Mithal, Divakar S.; Somogyi, Jason R.; Vien, Albert C.; Sánchez, Raúl Hernández; Koh, Sookyong

doi:10.1016/j.neulet.2020.134953

Cited by 11 publications

(6 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many reports have stated that glucocorticoids have a protective effect on neuronal loss in epilepsy models [20,42]. Therefore, we explored the changes in hippocampal neurons among groups.…”

Section: Discussionmentioning

confidence: 99%

Effects of Dexamethasone on Remodeling of the Hippocampal Synaptic Filamentous Actin Cytoskeleton in a Model of Pilocarpine-induced Status Epilepticus

et al. 2020

View full text Add to dashboard Cite

The filamentous actin (F-actin) cytoskeleton is progressively damaged after status epilepticus (SE), which is related to delayed neuronal death, aberrant recurrent circuits and epileptogenesis. Glucocorticoids regulate dendritic spine remodeling by acting on glucocorticoid receptors and the dynamics of the F-actin cytoskeleton. Our previous study showed that administration of dexamethasone (DEX) in the latent period of the pilocarpine epileptic model reduces damage to the hippocampal filamentous actin cytoskeleton and the loss of hippocampal neurons and aids in maintaining the synaptic structures, but it is not sufficient to stop epileptogenesis. In this work, we focused on the role of glucocorticoids in regulating the hippocampal F-actin cytoskeleton during SE. We examined the abundance of synaptic F-actin, analyzed the hippocampal F-actin/G-actin (F/G) ratio and pCofilin, and evaluated the number of hippocampal neurons and pre/postsynaptic markers in pilocarpine-induced status epilepticus mice with or without administration of dexamethasone (DEX). We found that the latency of Stage 3 seizures increased, the mortality decreased, the damage to the synaptic F-actin cytoskeleton in the hippocampal subfields was significantly attenuated, and a greater number of postsynaptic structures were retained in the hippocampal subfields after treatment with DEX. These results indicate that treatment with dexamethasone stabilizes the synaptic F-actin cytoskeleton and reduces the damage to the brain due to SE. This approach is expected to be beneficial in alleviating delayed neuron damage and the process of epileptogenesis.

show abstract

“…Many reports have stated that glucocorticoids have a protective effect on neuronal loss in epilepsy models [20,42]. Therefore, we explored the changes in hippocampal neurons among groups.…”

Section: Discussionmentioning

confidence: 99%

Effects of Dexamethasone on Remodeling of the Hippocampal Synaptic Filamentous Actin Cytoskeleton in a Model of Pilocarpine-induced Status Epilepticus

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Also, microglia near the injection site had larger cell bodies and a less ramified (i.e., reactive) morphology. In other studies that use an intraperitoneal injection of kainic acid, microglia were activated in the hippocampus when measured using microglia cell counts and percentage coverage of microglia ( Avignone et al, 2008 ; Fox et al, 2020 ). A higher number of microglial cells corresponds to a higher percentage coverage of Iba1 + staining, which is interpreted as greater microglial reactivity.…”

Section: Discussionmentioning

confidence: 99%

Reactive morphology of dividing microglia following kainic acid administration

et al. 2022

View full text Add to dashboard Cite

The microglial response to a pathological microenvironment is hallmarked by a change in cellular morphology. Following a pathological stimulus, microglia become reactive and simultaneously divide to create daughter cells. Although a wide array of microglial morphologies has been observed, the exact functions of these distinct morphologies are unknown, as are the morphology and reactivity status of dividing microglia. In this study, we used kainic acid to trigger microglial activation and cell division. Following a cortical kainic acid injection, microglial morphology and proliferation were examined at 3 days post-injection using immunohistochemistry for ionized calcium binding adapter molecule 1 (Iba1) to stain for microglia, and KI67 as a marker of cell division. Individual microglial cells were isolated from photomicrographs and skeletal and fractal analyses were used to examine cell size and spatial complexity. We examined the morphology of microglia in both wildtype and microglia-specific tumor necrosis factor (TNF)-α knockout mice. Data were analyzed using generalized linear mixed models or a two-way ANOVA. We found that dividing microglia had a more reactive morphology (larger cell body area, longer cell perimeter, and less ramification) compared to microglia that were not dividing, regardless of microglial release of TNF-α. However, we also observed dividing microglia with a complex, more ramified morphology. Changes in microglial morphology and division were greatest near the kainic acid injection site. This study uses robust and quantitative techniques to better understand microglial cell division, morphology, and population dynamics, which are essential for the development of novel therapeutics that target microglia.

show abstract

“…Recently, a variety of studies have indicated that activation of microglia induced by seizures in early life could aggravate susceptibility to seizures in later life [114][115][116]. Also, the activation of microglia in response to seizures is considered to be the crucial mediator of post-seizure cytokine production [117][118][119].…”

Section: Microglia and Epilepsymentioning

confidence: 99%

Crosstalk between peripheral and the brain-resident immune components in epilepsy

Mu¹,

Zhang²,

Gao³

et al. 2022

J. Integr. Neurosci.

View full text Add to dashboard Cite

Epilepsy is one of the most common neurology diseases. It is characterized by recurrent, spontaneous seizures and accompanied by various comorbidities which can significantly a fect a person's life. Accumulating evidence indicates an essential pathophysiological role for neuroin lammation in epilepsy, which involves activation of microglia and astrocytes, recruitment of peripheral leukocytes into the central nervous system, and release of some in lammatory mediators, including pro-in lammatory factors and anti-in lammatory cytokines. There is complex crosstalk between the central nervous system and peripheral immune responses associated with the progression of epilepsy. This review provides an update of current knowledge about the contribution of this crosstalk associated with epilepsy. Additionally, how gut microbiota is involved in epilepsy and its possible in luence on crosstalk is also discussed. Such recent advances in understanding suggest innovative methods for targeting the molecules correlated with the crosstalk and may provide a better prognosis for patients diagnosed with epilepsy.

show abstract

Dexamethasone after early-life seizures attenuates increased susceptibility to seizures, seizure-induced microglia activation and neuronal injury later in life

Cited by 11 publications

References 70 publications

Effects of Dexamethasone on Remodeling of the Hippocampal Synaptic Filamentous Actin Cytoskeleton in a Model of Pilocarpine-induced Status Epilepticus

Effects of Dexamethasone on Remodeling of the Hippocampal Synaptic Filamentous Actin Cytoskeleton in a Model of Pilocarpine-induced Status Epilepticus

Reactive morphology of dividing microglia following kainic acid administration

Crosstalk between peripheral and the brain-resident immune components in epilepsy

Contact Info

Product

Resources

About