Pharmacological and Therapeutic Approaches in the Treatment of Epilepsy

Ghosh, Shampa; Sinha, Jitendra Kumar; Khan, Tarab; Devaraju, K. S.; Singh, Prabhakar; Vaibhav, Kumar; Gaur, Pankaj

doi:10.3390/biomedicines9050470

Cited by 35 publications

(18 citation statements)

References 82 publications

(108 reference statements)

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“…However, each model has its own advantages and disadvantages compared with other models, and the appropriate model needs to be selected according to the experimental requirements. [36][37][38][39][40] All existing animal models have limitations, and they cannot fully simulate the characteristics of human TLE.…”

Section: Discussionmentioning

confidence: 99%

Ketogenic Diet Alleviates Hippocampal Neurodegeneration Possibly via ASIC1a and the Mitochondria-Mediated Apoptotic Pathway in a Rat Model of Temporal Lobe Epilepsy

Qiao¹,

Qu²,

Shuang³

et al. 2022

NDT

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Background The ketogenic diet (KD) is a proven therapy for refractory epilepsy. Although the anti-seizure properties of this diet are understood to a certain extent, the exploration of its neuroprotective effects and underlying mechanisms is still in its infancy. Tissue acidosis is a common feature of epileptogenic foci. Interestingly, the activation of acid-sensing ion channel 1a (ASIC1a), which mediates Ca 2+ -dependent neuronal injury during acidosis, has been found to be inhibited by ketone bodies in vitro. This prompted us to investigate whether the neuroprotective effects induced by the KD occur via ASIC1a and interconnected downstream mechanisms in a rat model of temporal lobe epilepsy. Methods Male Sprague-Dawley rats were fed either the KD or a normal diet for four weeks after undergoing pilocarpine-induced status epilepticus (SE). The effects of KD on epileptogenesis, cognitive impairment and hippocampal neuron injury in the epileptic rats were subsequently evaluated by video electroencephalogram, Morris water maze test and Nissl staining, respectively. The expression of ASIC1a and cleaved caspase-3 in the hippocampus were determined using Western blot analysis during the chronic period following SE. Moreover, the intracellular Ca 2+ concentration, mitochondrial membrane potential (MMP), mitochondrial reactive oxygen species (mROS) and cell apoptosis of hippocampal cells were detected by flow cytometry. Results We found that the KD treatment strongly attenuated the spontaneous recurrent seizures, ameliorated learning and memory impairments and prevented hippocampal neuronal injury and apoptosis. The KD was also shown to inhibit the upregulation of ASIC1a and the ensuing intracellular Ca 2+ overload in the hippocampus of the epileptic rats. Furthermore, the seizure-induced structure disruption of neuronal mitochondria, loss of MMP and accumulation of mROS were reversed by the KD treatment, suggesting that it has protective effects on mitochondria. Finally, the activation of caspase-3 was also inhibited by the KD. Conclusion These findings indicate that the KD suppresses mitochondria-mediated apoptosis possibly by regulating ASIC1a to exert neuroprotective effects. This may provide a mechanistic explanation of the therapeutic effects of KD.

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Section: Discussionmentioning

confidence: 99%

Ketogenic Diet Alleviates Hippocampal Neurodegeneration Possibly via ASIC1a and the Mitochondria-Mediated Apoptotic Pathway in a Rat Model of Temporal Lobe Epilepsy

Qiao¹,

Qu²,

Shuang³

et al. 2022

NDT

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“…Current anti-epileptic drugs primarily target glutamate receptors or GABA receptors, thereby inhibiting seizures. However, long-term drug therapy may produce severe side effects, and some patients still develop drug resistance ( Ghosh et al, 2021 ). Approximately 30–40% of people with epilepsy are resistant to traditional anti-epileptic drugs ( Li et al, 2022 ).…”

Section: Potential Of Medial Ganglionic Eminence Cell Transplantation...mentioning

confidence: 99%

Application of Medial Ganglionic Eminence Cell Transplantation in Diseases Associated With Interneuron Disorders

Han

2022

Front. Cell. Neurosci.

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Excitatory projection neurons and inhibitory interneurons primarily accomplish the neural activity of the cerebral cortex, and an imbalance of excitatory-inhibitory neural networks may lead to neuropsychiatric diseases. Gamma-aminobutyric acid (GABA)ergic interneurons mediate inhibition, and the embryonic medial ganglionic eminence (MGE) is a source of GABAergic interneurons. After transplantation, MGE cells migrate to different brain regions, differentiate into multiple subtypes of GABAergic interneurons, integrate into host neural circuits, enhance synaptic inhibition, and have tremendous application value in diseases associated with interneuron disorders. In the current review, we describe the fate of MGE cells derived into specific interneurons and the related diseases caused by interneuron loss or dysfunction and explore the potential of MGE cell transplantation as a cell-based therapy for a variety of interneuron disorder-related diseases, such as epilepsy, schizophrenia, autism spectrum disorder, and Alzheimer’s disease.

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“…Some underlying genetic factors, brain injuries, tumours, or dysregulated microRNAs have been identified to be the cause of epilepsy, but in 60% of the cases, the source is unknown [ 58 ]. Substantial progress has been made in terms of treatment, comprising anti-convulsants [ 59 ], neuromodulation [ 60 ], and dietary regulations, such as ketogenic diet [ 61 ]. Nonetheless, about a third of patients continue to experience seizures [ 61 ], leaving surgery as the sole remaining option.…”

Section: Also In This Issuementioning

confidence: 99%

This is not a pipe – But how harmful is electronic cigarette smoke

Häfner

2021

Biomedical Journal

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This issue of the Biomedical Journal tells us about the risks of electronic cigarette smoking, variations of SARS-CoV-2 and ACE2, and how COVID-19 affects the gastrointestinal system. Moreover, we learn that cancer immunotherapy seems to work well in elderly patients, how thyroid hormones regulate noncoding RNAs in a liver tumour context, and that G6PD is a double-edged sword of redox signalling. We also discover that Perilla leaf extract could inhibit SARS-CoV-2, that artificial neural networks can diagnose COVID-19 patients and predict vaccine epitopes on the Epstein–Barr Virus, and that men and women have differential inflammatory responses to physical effort. Finally, the surgical strategies for drug-resistant epilepsy, computer-supervised double-jaw surgery, dental pulp stem cell motility, and the restitution of the brain blood supply after atherosclerotic stroke are discussed.

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Pharmacological and Therapeutic Approaches in the Treatment of Epilepsy

Cited by 35 publications

References 82 publications

Ketogenic Diet Alleviates Hippocampal Neurodegeneration Possibly via ASIC1a and the Mitochondria-Mediated Apoptotic Pathway in a Rat Model of Temporal Lobe Epilepsy

Ketogenic Diet Alleviates Hippocampal Neurodegeneration Possibly via ASIC1a and the Mitochondria-Mediated Apoptotic Pathway in a Rat Model of Temporal Lobe Epilepsy

Application of Medial Ganglionic Eminence Cell Transplantation in Diseases Associated With Interneuron Disorders

This is not a pipe – But how harmful is electronic cigarette smoke

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