planarian-as-an-animal-model-for-experimental-acute-seizure

Planarian as an Animal Model for Experimental Acute Seizure

Epilepsy is among the most prevalent neurological disorders characterized by recurring spontaneous seizures. Seizures represent a clinical manifestation ...

Old Dominion University

Status epilepticus (SE) is a medical emergency characterized by uncontrolled, prolonged seizures with rapid and widespread neuronal damage. Patients that suffer from longer episodes of SE are more likely to have poorer clinical outcomes and a higher cost of healthcare. Understanding novel molecular mechanisms that regulate inhibitory and excitatory neurotransmission that initiate SE and the necessary medical infrastructure to stop SE could help identify targets for early intervention. Intranasal administration of benzodiazepines may shorten the time between initiation and cessation of seizures when compared to other routes of administration. Current pharmaceutical administration guidelines are appropriate for sporadic incidences of SE, but exploring other approaches is necessary to prepare for situations involving multiple patients outside of a hospital, such as a massive chemical weapons attack. Intranasal drug delivery helps to circumvent the blood-brain barrier and offers a noninvasive way to quickly administer drugs in settings that require an immediate response, such as nerve agent exposure. In addition, examining the intranasal delivery of new drugs, such as nanotherapeutics, may lead to more effective, noninvasive, scalable, and portable methods of treating SE.

Intranasal Therapy to Stop Status Epilepticus in Prehospital Settings.

Epilepsy, a neurological disease characterized by recurrent seizures, is often associated with a history of previous lesions in the nervous system. Impaired regulation of the activation and resolution of inflammatory cells and molecules in the injured neuronal tissue is a critical factor to the development of epilepsy. However, it is still unclear as to how that unbalanced regulation of inflammation contributes to epilepsy. Therefore, one of the goals in epilepsy research is to identify and elucidate the interconnected inflammatory pathways in systemic and neurological disorders that may further develop epilepsy progression. In this paper, inflammatory molecules, in neurological and systemic disorders (rheumatoid arthritis, Crohn's, Type I Diabetes, etc.) that could contribute to epilepsy development, are reviewed.Understanding the neurobiology of inflammation in epileptogenesis will contribute to the development of new biomarkers for better screening of patients at risk for epilepsy and new therapeutic targets for both prophylaxis and treatment of epilepsy.

The role of inflammation in the development of epilepsy.

Development of epilepsy or epileptogenesis promotes recurrent seizures. As of today, there are no effective prophylactic therapies to prevent the onset of epilepsy. Contributing to this deficiency of preventive therapy is the lack of clarity in fundamental neurobiological mechanisms underlying epileptogenesis and lack of reliable biomarkers to identify patients at risk for developing epilepsy. This limits the development of prophylactic therapies in epilepsy. Here, neural network dysfunctions reflected by oscillopathies and microepileptiform activities, including neuronal hyperexcitability and hypersynchrony, drawn from both clinical and experimental epilepsy models, have been reviewed. This review suggests that epileptogenesis reflects a progressive and dynamic dysfunction of specific neuronal networks which recruit further interconnected groups of neurons, with this resultant pathological network mediating seizure occurrence, recurrence, and progression. In the future, combining spatial and temporal resolution of neuronal non-invasive recordings from patients at risk of developing epilepsy, together with analytics and computational tools, may contribute to determining whether the brain is undergoing epileptogenesis in asymptomatic patients following brain injury.

Brain injuries can set up an epileptogenic neuronal network.

Unregulated neuro-inflammation mediates seizures in temporal lobe epilepsy (TLE). Our aim was to determine the effect of CD40-CD40L activation in experimental seizures. CD40 deficient mice (CD40KO) and control mice (wild type, WT) received pentenyltetrazole (PTZ) or pilocarpine to evaluate seizures and status epilepticus (SE) respectively. In mice, anti-CD40L antibody was administered intranasally before PTZ. Brain samples from human TLE and post-seizure mice were processed to determine CD40-CD40L expression using histological and molecular techniques. CD40 expression was higher in hippocampus from human TLE and in cortical neurons and hippocampal neural terminals after experimental seizures. CD40-CD40L levels increased after seizures in the hippocampus and in the cortex. After SE, CD40L/CD40 levels increased in cortex and showed an upward trend in the hippocampus. CD40KO mice demonstrated reduction in seizure severity and in latency compared to WT mice. Anti-CD40L antibody limited seizure susceptibility and seizure severity. CD40L-CD40 interaction can serve as a target for an immuno-therapy for TLE.

Article	Year
Intranasal Therapy to Stop Status Epilepticus in Prehospital Settings. Drugs in R&D\| PubMed ID: 29177587	2018
The role of inflammation in the development of epilepsy. Journal of neuroinflammation\| PubMed ID: 29764485	2018
Brain injuries can set up an epileptogenic neuronal network. Neuroscience and biobehavioral reviews\| PubMed ID: 34384843	2021
Downregulation of CD40L-CD40 attenuates seizure susceptibility and severity of seizures. Scientific reports\| PubMed ID: 34446808	2021
Author Correction: Downregulation of CD40L-CD40 attenuates seizure susceptibility and severity of seizures. Scientific reports\| PubMed ID: 34824309	2021

Alberto E. Musto

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