use-wireless-video-eeg-system-to-monitor-epileptiform-discharges

Use of a Wireless Video-EEG System to Monitor Epileptiform Discharges Following Lateral Fluid-Percussion Induced Traumatic Brain Injury

The lateral fluid percussion injury (FPI) model is well established and has been used to study TBI and post-traumatic epilepsy (PTE). However, ...

Jacobs School of Medicine and Biomedical Science

Preclinical and clinical studies can be greatly improved through the inclusion of diagnostic, prognostic, predictive or pharmacodynamics biomarkers. Circulating microRNAs (miRNAs) represent highly stable targets that respond to physiological and pathological changes. MicroRNA biomarkers can be detected by highly sensitive and absolutely quantitative methods currently available in most clinical laboratories. Here we review preclinical and clinical studies that have examined circulating miRNAs as potential diagnostic and prognostic biomarkers. We also present data that suggests pharmacodynamics biomarkers can be identified that are associated with neuroprotection in general. Although circulating miRNA can serve as useful tools, it is clear their expression profiles are highly sensitive to changing conditions and are influenced by a broad range of parameters including age, sex, body mass index, injury severity, time of collection, as well as methods of processing, purification and detection. Thus, considerable effort will be required to standardize methods and experimental design conditions before circulating miRNAs can prove useful in a heterologous injury like TBI. This article is part of the Special Issue entitled "Novel Treatments for Traumatic Brain Injury".

Circulating microRNAs as biomarkers in traumatic brain injury.

The rat lateral fluid-percussion injury (FPI) model has been used extensively to study post-traumatic epilepsy (PTE). Epidemiological studies have reported that the risk of PTE is higher after more severe injury. Adult, male Wistar rats subjected to different atmospheric pressures of injury during FPI showed great variability in injury severity when functional behavior was determined based on the Neurological Severity Score (NSS) assessment. When NSS was used to select rats with the most severe FPI-induced brain injury, 63% of rats experienced at least one convulsive seizure 2-5 weeks after FPI. This same cohort of rats (i.e., selected for severe TBI based on NSS) were significantly more susceptible to PTZ-induced seizures compared to sham controls. Video/EEG recordings from a second cohort of rats with severe FPI-induced injury (based on NSS) showed a similar incidence and frequency of spike wave discharges between rats with severe TBI and sham controls. However, the rate of isolated EEG spikes was greater in rats with severe FPI-induced injury compared to sham controls. These data suggest that convulsive seizures can be obtained in FPI-treated rats when NSS is used as an inclusion criterion to select rats with severe injury. Furthermore, although spike-wave discharges were equally prevalent in rats with severe FPI and sham controls, spontaneous spikes were more prevalent in the rats with severe FPI.

Convulsive seizures and EEG spikes after lateral fluid-percussion injury in the rat.

Extracellular vesicles (EVs) are small vesicles involved in intercellular communication. Data is emerging that EVs and their cargo have potential as diagnostic biomarkers and treatments for brain diseases, including traumatic brain injury and epilepsy. Here, we summarize the current knowledge regarding changes in EV numbers and cargo in status epilepticus (SE) and traumatic brain injury (TBI), which are clinically significant etiologies for acquired epileptogenesis in animals and humans. We also review encouraging data, which suggests that EVs secreted by stem cells may serve as recovery-enhancing treatments for SE and TBI. Using Gene Set Enrichment Analysis, we show that brain EV-related transcripts are positively enriched in rodent models of epileptogenesis and epilepsy, and altered in response to anti-seizure drugs. These data suggest that EVs show promise as biomarkers, treatments and drug targets for epilepsy. In parallel to gathering conceptual knowledge, analytics platforms for the isolation and analysis of EV contents need to be further developed.

Article	Year
Circulating microRNAs as biomarkers in traumatic brain injury. Neuropharmacology\| PubMed ID: 30195586	2019
Convulsive seizures and EEG spikes after lateral fluid-percussion injury in the rat. Epilepsy research\| PubMed ID: 30286390	2018
Extracellular Vesicles as Diagnostics and Therapeutics for Structural Epilepsies. International journal of molecular sciences\| PubMed ID: 30871144	2019

David J. Poulsen

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