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Advanced Neurology Non-invasive electroencephalography in rats

• Childhood absence epilepsy is characterized by the rats, 12-15 as well as in relatively healthy rat strains, such as
occurrence of 3-Hz (range = 2.5 – 4 Hz) generalized Sprague Dawley, Long Evans and Wistar rats. 12,16-20 WAG/
SWDs. If no generalized SWDs are elicited following Rij and GAERS strains, which are derived from Wistar
3 min of hyperventilation in an untreated patient, rats, have been recognized as valid, reliable, and predictive
childhood absence epilepsy can be excluded models of human absence epilepsy. Here, we used the WAG/
• Juvenile absence epilepsy is characterized by the Rij rat genetic model of absence epilepsy, 8-11 in which SWDs
occurrence of regular 3 – 5.5-Hz generalized appear spontaneously and are associated with absence-like
SWDs. If no SWDs are observed after performing behavior. The WAG/Rij genetic model provides several
hyperventilation for 3 min in an untreated patient, advantages over chemical models of epilepsy in rodents
juvenile absence epilepsy can be ruled out (The Discussion section for more details). Two technical
• Juvenile myoclonic epilepsy is characterized by the approaches were employed to execute our study in vivo: (1)
occurrence of irregular, generalized 3 – 5.5-Hz SWDs traditional electrocorticographic (ECoG) examination in
and polyspike-wave discharges. free behavior using implanted epidural electrodes and (2)
Animal models are frequently employed in basic a newly devised non-invasive EEG technique for the rapid
and preclinical studies of absence epilepsy because of diagnosis of absence epilepsy in rats.
ethical concerns associated with research engaging Epidural ECoG is a valuable tool for analyzing brain
human participants. Absence epilepsy can be studied in activity and is recommended for preclinical investigation
various animal models, including electrical stimulation in genetic rat models. In patients with refractory epilepsy,
11
models, pharmacological treatment models, and genetic ECoG serves as the primary standard for precisely
models (References in Jafarian et al. ). The following identifying the exact seizure onset zones that require
6
pharmacological compounds can induce typical absence surgical removal. ECoG generates exceptionally high-
21
seizures in rodents and cats: penicillin at high doses quality and more stable signals with exceedingly high-
(250,000 – 6,000,000 U/kg), pentylenetetrazole (PTZ) at precision spatial resolution than the non-invasive EEG
low doses (20 – 30 mg/kg intraperitoneally), and gamma- method. Although minimally invasive, the ECoG method
hydroxybutyrate at a dose of 200 mg/kg intravenously. offers numerous advantages. First, it generates high-
6,7
Pharmacological animal models of absence epilepsy can be resolution ECoG signals, capturing complex neural activity
classified into two categories: acute and chronic. across the brain’s surface. Second, it facilitates prolonged
• In acute models, a pharmacological agent is recordings, enabling the monitoring of brain activity
administered to induce absence seizures for a brief over extended periods. Finally, ECoG is compatible with
period. These models are valuable for examining the neuroimaging techniques, such as functional magnetic
immediate effects of drugs on absence seizures and for resonance imaging and magnetoencephalography, thereby
discovering novel treatments enhancing the results’ interpretive power.
• In chronic models, absence seizures are induced by
administering a pharmacological agent over a long Considering that absence-like seizures can manifest
12,16-20
period. These models are beneficial for studying the in relatively healthy rat strains. and the correlation
long-term effects of drugs on absence seizures and for of absence epilepsy in rats with neurobehavioral
identifying potential adverse effects. comorbidities, 22-24 there is a need for non-invasive EEG-
based diagnostic tools in rats. EEG-based techniques can
As idiopathic generalized epilepsies, including provide a rapid and reliable diagnosis of epilepsy while
childhood absence epilepsy, have a multifactorial genetic safeguarding the rats. In this study, we used the principle of
cause, genetic animal models are considered more pharmacological induction of SWDs, as previously described
suitable than chemical models. In contrast to externally by our research group, 25,26 to diagnose the absence epilepsy
induced SWDs in chemical or electrical epilepsy models, in rats. In particular, the systemic administration of low
genetic animal models demonstrate spontaneous SWDs doses of alpha2-adrenoreceptor agonists (such as xylazine,
due to their genetic predisposition. Notably, the EEG dexmedetomidine, and medetomidine) is known to induce
characteristics of SWDs and the associated behavioral signs recurrent, long-lasting SWDs in WAG/Rij rats. However, it
in the genetic animal models closely resemble the EEG and did not elicit de novo SWDs in non-epileptic subjects. The
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clinical manifestations observed in human patients. intraperitoneal injection of low-dose dexmedetomidine
SWDs occur spontaneously during absence-like seizures (dose range, 0.0035 – 0.0307 mg/kg) in symptomatic
in genetic rat models of absence epilepsy, including the WAG/Rij rats induced an absence-like behavioral state
Wistar Albino Glaxo from Rijswijk (WAG/Rij rats) 8-11 and and elevated SWDs shortly after injection (with durations
Genetic Absence Epilepsy Rats from Strasburg (GAERS) ranging from 68 s to 6.6 min). In 1990, Buzsáki et al. revealed
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Volume 3 Issue 4 (2024) 2 doi: 10.36922/an.4464