scholarly journals Neuronal kinase SGK1.1 protects against brain damage after status epilepticus

2020 ◽  
Author(s):  
Elva Martin-Batista ◽  
Laura E. Maglio ◽  
Natalia Armas-Capote ◽  
Guadalberto Hernandez ◽  
Diego Alvarez de la Rosa ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Brain Damage ◽  
Neuronal Death ◽  
Neuronal Excitability ◽  
Neuroprotective Effect ◽  
Protective Role ◽  
Brain Diseases ◽  
M Current ◽  
Current Activation

ABSTRACTEpilepsy is a neurological condition associated to significant brain damage produced by status epilepticus (SE) including neurodegeneration, gliosis and ectopic neurogenesis. Reduction of these processes constitutes a useful strategy to improve recovery and ameliorate negative outcomes after an initial insult. SGK1.1, the neuronal isoform of the serum and glucocorticoids-regulated kinase 1 (SGK1), has been shown to increase M-current density in neurons, leading to reduced excitability and protection against seizures. We now show that SGK1.1 activation potently reduces levels of neuronal death and gliosis after SE induced by kainate, even in the context of high seizure activity. This neuroprotective effect is not exclusively a secondary effect of M-current activation but is also directly linked to decreased apoptosis levels through regulation of Bim and Bcl-xL cellular levels. Our results demonstrate that this newly described antiapoptotic role of SGK1.1 activation acts synergistically with the regulation of cellular excitability, resulting in a significant reduction of SE-induced brain damage. The protective role of SGK1.1 occurs without altering basal neurogenesis in brain areas relevant to epileptogenesis.SIGNIFICANCE STATEMENTApproaches to control neuronal death and inflammation are of increasing interest in managing epilepsy, one of the most important idiopathic brain diseases. We have previously shown that activation of SGK1.1 reduces neuronal excitability by increasing M-current levels, significantly reducing seizure severity. We now describe a potent neuroprotective role of SGK1.1, which dramatically reduces neuronal death and gliosis after status epilepticus. This effect is partially dependent on M-current activation and includes an additional anti-apoptotic role of SGK1.1. Our data strongly support the relevance of this kinase as a potential target for epilepsy treatment.

scholarly journals The Neuroprotective Effect of Hericium erinaceus Extracts in Mouse Hippocampus after Pilocarpine-Induced Status Epilepticus

2019 ◽  
Vol 20 (4) ◽  
pp. 859 ◽  
Author(s):  
Hyun-Jong Jang ◽  
Ji-Eun Kim ◽  
Kyoung Jeong ◽  
Sung Lim ◽  
Seong Kim ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Neuronal Death ◽  
Therapeutic Potential ◽  
Neuroprotective Effect ◽  
Brain Diseases ◽  
Cresyl Violet ◽  
Neuroprotective Effects ◽  
Hericium Erinaceus ◽  
Neuronal Nuclei ◽  
Underlying Mechanisms

Hericium erinaceus (HE), a culinary-medicinal mushroom, has shown therapeutic potential in many brain diseases. However, the role of HE in status epilepticus (SE)-mediated neuronal death and its underlying mechanisms remain unclear. We investigated the neuroprotective effects of HE using a pilocarpine-induced SE model. Male C57BL/6 mice received crude extracts of HE (60 mg/kg, 120 mg/kg, or 300 mg/kg, p.o.) for 21 d from 14 d before SE to 6 d after SE. At 7 d after SE, cresyl violet and immunohistochemistry of neuronal nuclei revealed improved hippocampal neuronal survival in animals treated with 60 mg/kg and 120 mg/kg of HE, whereas those treated with 300 mg/kg of HE showed similar neuronal death to that of vehicle-treated controls. While seizure-induced reactive gliosis, assessed by immunohistochemistry, was not altered by HE, the number of hippocampal cyclooxygenase 2 (COX2)-expressing cells was significantly reduced by 60 and 120 mg/kg of HE. Triple immunohistochemistry demonstrated no overlap of COX2 labeling with Ox42, in addition to a decrease in COX2/GFAP-co-immunoreactivity in the group treated with 60 mg/kg HE, suggesting that the reduction of COX2 by HE promotes neuroprotection after SE. Our findings highlight the potential application of HE for preventing neuronal death after seizures.

scholarly journals The potential neuroprotective effect of allicin and melatonin in acrylamide-induced brain damage in rats

2021 ◽  
Author(s):  
Hanan A. Edres ◽  
Nabil M. Taha ◽  
Mohamed A. lebda ◽  
Mohamed S. Elfeky
Keyword(s):  
Brain Damage ◽  
Neuroprotective Effect ◽  
Brain Dysfunction ◽  
Protective Role ◽  
Adult Rats ◽  
Male Adult ◽  
Antioxidative Status ◽  
The Brain ◽  
Necrosis Factor

Abstract Acrylamide (ACR) is an unsaturated monomer that entered in various fields however, it is a potent neurotoxic. The present study target is to explore the neuroprotective efficacy of allicin and melatonin on ACR-induced neurotoxicity. Thirty-six male adult rats were non-selectively separated into six groups: placebo, allicin (20 mg/kg b.w daily per os), melatonin (10 mg/kg b.w 3 times/week per os), ACR (50 mg/kg b.w daily per os), ACR + allicin and ACR + melatonin with the same doses. The assessment of brain biomarkers, neurotransmitters, antioxidative status, Nrf2 signalling pathway, and histopathological analyses were performed following 21 days. ACR exposure enhanced the brain lipid and DNA oxidative damage as well as a reduction in the GSH levels. The obvious brain oxidative injuries was contributed to distinct brain dysfunction that was assured by alteration of brain neurotransmitters (serotonin, dopamine, acetylcholine, and acetylcholinesterase), and pathological brain lesions. Furthermore, ACR exposure increased hydroxy deoxy guanosine (8-OHdG), tumor necrosis factor (TNF) and amyloid protein (AB-42). Finally, the mRNA transcripts of brain Keap-1, Nrf2, and NF-kB were up regulated after ACR intoxication. Interestingly, allicin and melatonin alleviated the ACR-induced brain damage assessed by normalization of the mentioned analyses. The present study demonstrated the protective role of both allicin and melatonin on ACR-prompted neuropathy by alleviation of redox imbalance and enhancement of neurotransmitters as well as relieving DNA damage and anti-inflammatory effect.

scholarly journals Protective Role of Glutathione in the Hippocampus after Brain Ischemia

2021 ◽  
Vol 22 (15) ◽  
pp. 7765
Author(s):  
Youichirou Higashi ◽  
Takaaki Aratake ◽  
Takahiro Shimizu ◽  
Shogo Shimizu ◽  
Motoaki Saito
Keyword(s):  
Oxidative Stress ◽  
Neuronal Death ◽  
Excitatory Amino Acid ◽  
Ischemia Reperfusion ◽  
Thiol Group ◽  
Protective Role ◽  
Key Factor ◽  
Rate Limiting ◽  
Cysteine Uptake

Stroke is a major cause of death worldwide, leading to serious disability. Post-ischemic injury, especially in the cerebral ischemia-prone hippocampus, is a serious problem, as it contributes to vascular dementia. Many studies have shown that in the hippocampus, ischemia/reperfusion induces neuronal death through oxidative stress and neuronal zinc (Zn2+) dyshomeostasis. Glutathione (GSH) plays an important role in protecting neurons against oxidative stress as a major intracellular antioxidant. In addition, the thiol group of GSH can function as a principal Zn2+ chelator for the maintenance of Zn2+ homeostasis in neurons. These lines of evidence suggest that neuronal GSH levels could be a key factor in post-stroke neuronal survival. In neurons, excitatory amino acid carrier 1 (EAAC1) is involved in the influx of cysteine, and intracellular cysteine is the rate-limiting substrate for the synthesis of GSH. Recently, several studies have indicated that cysteine uptake through EAAC1 suppresses ischemia-induced neuronal death via the promotion of hippocampal GSH synthesis in ischemic animal models. In this article, we aimed to review and describe the role of GSH in hippocampal neuroprotection after ischemia/reperfusion, focusing on EAAC1.

Excitotoxic brain damage involves early peroxynitrite formation in a model of Huntington’s disease in rats: Protective role of iron porphyrinate 5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinate iron (III)

Neuroscience ◽  
2005 ◽  
Vol 135 (2) ◽  
pp. 463-474 ◽  
Author(s):  
V. Pérez-De La Cruz ◽  
C. González-Cortés ◽  
S. Galván-Arzate ◽  
O.N. Medina-Campos ◽  
F. Pérez-Severiano ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Brain Damage ◽  
Protective Role

scholarly journals Conditional Upregulation of KCC2 selectively enhances neuronal inhibition during seizures

2018 ◽  
Author(s):  
CS Goulton ◽  
M Watanabe ◽  
DL Cheung ◽  
KW Wang ◽  
T Oba ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Transgenic Mouse ◽  
Brain Function ◽  
Neuronal Excitability ◽  
Hippocampal Slices ◽  
Transport Function ◽  
Neuronal Inhibition ◽  
Proof Of Principle

Abstract/SummaryEfficacious neuronal inhibition is sustained by the neuronal K+Cl- co-transporter KCC2, and loss of KCC2 function through injury or mutation is associated with altered GABAergic signalling and neuronal seizures. Here we report a transgenic mouse with conditional KCC2 overexpression that results in increased membrane transport function. Increased KCC2 has little impact on behavioural and in vitro assays of neuronal excitability and GABAA receptor responses under resting conditions. In contrast, increased KCC2 imparts resistance to seizure-like neuronal activity in hippocampal slices and prevents the progression of mice into behavioural status epilepticus following multiple kainic acid doses. Our results demonstrate a transgenic mouse to facilitate investigations into the role of KCC2 in brain function, and provide a proof of principle that targeting KCC2 may be an effective way to selectively enhance neuronal inhibition to mitigate against diseases that involve an imbalance between excitation and inhibition.

Neuroprotective role of 6-Gingerol-rich fraction of Zingiber officinale (Ginger) against acrylonitrile-induced neurotoxicity in male Wistar rats

2018 ◽  
Vol 30 (3) ◽  
Author(s):  
Ebenezer Olatunde Farombi ◽  
Amos Olalekan Abolaji ◽  
Babatunde Oluwafemi Adetuyi ◽  
Olaide Awosanya ◽  
Mobolaji Fabusoro
Keyword(s):  
Brain Damage ◽  
Corn Oil ◽  
Zingiber Officinale ◽  
Protective Role ◽  
Male Rats ◽  
Cortex Lesion ◽  
Male Wistar Rats ◽  
Group B ◽  
Factor Α

Abstract Background Acrylonitrile (AN) is a neurotoxin that is widely used to manufacture synthetic fibres, plastics and beverage containers. Recently, we reported the ameliorative role of 6-gingerol-rich fraction from Zingiber officinale (Ginger, GRF) on the chlorpyrifos-induced toxicity in rats. Here, we investigated the protective role of GRF on AN-induced brain damage in male rats. Methods Male rats were orally treated with corn oil (2 mL/kg, control), AN (50 mg/kg, Group B), GRF (200 mg/kg, Group C), AN [50 mg/kg+GRF (100 mg/kg) Group D], AN [(50 mg/kg)+GRF (200 mg/kg) Group E] and AN [(50 mg/kg)+N-acetylcysteine (AC, 50 mg/kg) Group F] for 14 days. Then, we assessed the selected markers of oxidative damage, antioxidant status and inflammation in the brain of rats. Results The results indicated that GRF restored the AN-induced elevations of brain malondialdehyde (MDA), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and Nitric Oxide (NO) levels. GRF also prevented the AN-induced depletion of brain glutathione (GSH) level and the activities of Glutathione S-transferase (GST), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in rats (p<0.05). Furthermore, GRF prevented the AN-induced cerebral cortex lesion and increased brain immunohistochemical expressions of Caspases-9 and -3. Conclusions Our data suggest that GRF may be a potential therapeutic agent in the treatment of AN-induced model of brain damage.

scholarly journals Melatonin and Ischemic Stroke: Mechanistic Roles and Action

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Syed Suhail Andrabi ◽  
Suhel Parvez ◽  
Heena Tabassum
Keyword(s):  
Ischemic Stroke ◽  
Brain Injury ◽  
Neurological Diseases ◽  
Neuroprotective Effect ◽  
Economic Loss ◽  
Protective Role ◽  
Physiological Processes ◽  
Cord Injury ◽  
The Brain

Stroke is one of the most devastating neurological disabilities and brain’s vulnerability towards it proves to be fatal and socio-economic loss of millions of people worldwide. Ischemic stroke remains at the center stage of it, because of its prevalence amongst the several other types attacking the brain. The various cascades of events that have been associated with stroke involve oxidative stress, excitotoxicity, mitochondrial dysfunction, upregulation of Ca2+level, and so forth. Melatonin is a neurohormone secreted by pineal and extra pineal tissues responsible for various physiological processes like sleep and mood behaviour. Melatonin has been implicated in various neurological diseases because of its antioxidative, antiapoptotic, and anti-inflammatory properties. We have previously reviewed the neuroprotective effect of melatonin in various models of brain injury like traumatic brain injury and spinal cord injury. In this review, we have put together the various causes and consequence of stroke and protective role of melatonin in ischemic stroke.

scholarly journals Getting to NO Alzheimer’s Disease: Neuroprotection versus Neurotoxicity Mediated by Nitric Oxide

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Rachelle Balez ◽  
Lezanne Ooi
Keyword(s):  
Nitric Oxide ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathways ◽  
Neuronal Excitability ◽  
Neurodegenerative Disorder ◽  
Memory Loss ◽  
Protective Role ◽  
Ionic Mechanisms

Alzheimer’s disease (AD) is a neurodegenerative disorder involving the loss of neurons in the brain which leads to progressive memory loss and behavioral changes. To date, there are only limited medications for AD and no known cure. Nitric oxide (NO) has long been considered part of the neurotoxic insult caused by neuroinflammation in the Alzheimer’s brain. However, focusing on early developments, prior to the appearance of cognitive symptoms, is changing that perception. This has highlighted a compensatory, neuroprotective role for NO that protects synapses by increasing neuronal excitability. A potential mechanism for augmentation of excitability by NO is via modulation of voltage-gated potassium channel activity (Kv7 and Kv2). Identification of the ionic mechanisms and signaling pathways that mediate this protection is an important next step for the field. Harnessing the protective role of NO and related signaling pathways could provide a therapeutic avenue that prevents synapse loss early in disease.

scholarly journals Deficiency of autism risk factor ASH1L in prefrontal cortex induces epigenetic aberrations and seizures

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Luye Qin ◽  
Jamal B. Williams ◽  
Tao Tan ◽  
Tiaotiao Liu ◽  
Qing Cao ◽  
...  
Keyword(s):  
Risk Factor ◽  
Prefrontal Cortex ◽  
Neuronal Excitability ◽  
Critical Role ◽  
Treatment Strategies ◽  
Autism Spectrum ◽  
Synaptic Function ◽  
Brain Diseases ◽  
Risk Genes

AbstractASH1L, a histone methyltransferase, is identified as a top-ranking risk factor for autism spectrum disorder (ASD), however, little is known about the biological mechanisms underlying the link of ASH1L haploinsufficiency to ASD. Here we show that ASH1L expression and H3K4me3 level are significantly decreased in the prefrontal cortex (PFC) of postmortem tissues from ASD patients. Knockdown of Ash1L in PFC of juvenile mice induces the downregulation of risk genes associated with ASD, intellectual disability (ID) and epilepsy. These downregulated genes are enriched in excitatory and inhibitory synaptic function and have decreased H3K4me3 occupancy at their promoters. Furthermore, Ash1L deficiency in PFC causes the diminished GABAergic inhibition, enhanced glutamatergic transmission, and elevated PFC pyramidal neuronal excitability, which is associated with severe seizures and early mortality. Chemogenetic inhibition of PFC pyramidal neuronal activity, combined with the administration of GABA enhancer diazepam, rescues PFC synaptic imbalance and seizures, but not autistic social deficits or anxiety-like behaviors. These results have revealed the critical role of ASH1L in regulating synaptic gene expression and seizures, which provides insights into treatment strategies for ASH1L-associated brain diseases.

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