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Advanced Neurology Non-invasive electroencephalography in rats

four subjects (25% from the group, marked with red dots minutes and were interrupted by brief periods of
in Figure 5) exhibited a low number of SWDs at baseline desynchronization (Figure 6C).
and mild SWDs following xylazine administration (25 –
100s out of the 6-min observation period, or 8 – 33%). 3.4. Xylazine-based tests for diagnosing absence
The remaining eight rats (50% from the group, marked epilepsy
with blue dots in Figure 5) exhibited SWDs at baseline and Non-invasive EEG examinations under a xylazine-induced
severe SWDs after xylazine injections (more than 100 s out state were performed in the second group of rats (n = 65)
of the 6-min observation period or more than 33%). between 5 and 15 months of age. Based on the results of
In conclusion, we observed a remarkably high level EEG-based assessments, the rats were diagnosed with
of consistency between the total duration of spontaneous three categories of epileptic conditions: asymptomatic,
SWDs and that of xylazine-induced SWDs. Therefore, mild, and severe. Figure 7 demonstrates the diagnostic
the severity of xylazine-induced epileptic manifestations results grouped by the following age ranges: 5 – 7 months,
was remarkably similar to that of the baseline condition. 7 – 9 months, and older than 9 months.
The findings indicate that xylazine injections could be a Twenty-six rats were tested multiple times at varying
valuable tool for diagnosing absence epilepsy in rats. On ages. Among them, six rats (23%) were characterized by
invasive ECoG examination of the first group (n = 16), an age-related increase in the severity of absence epilepsy.
three major epileptic phenotypes were revealed, including Nine rats (35%) showed no age-related changes in the
asymptomatic (25%), mild epilepsy (25%), and severe severity of epilepsy. Eleven rats (42%) were asymptomatic.
epilepsy (50%). None (0%) of the rats demonstrated a reduction in the
severity of absence epilepsy.
3.3. Non-invasive EEG examination in rats under
xylazine 4. Discussion
The second group of rats (n = 65) was subjected to non- In this study, we present a novel EEG-based diagnostic
invasive EEG examination. Each rat was administered method for the rapid diagnosis of absence epilepsy. This
xylazine intraperitoneally (dose: 8 mg/kg) to induce method utilizes the sedative effects of xylazine and its
sedation and provoke epileptic spike-wave activity. EEG distinct ability to induce SWDs in rats with spontaneous
recordings were obtained for more than 6 min after the SWDs. To validate this method, we implanted WAG/Rij
injection. The rats remained immobile during the EEG rats (n = 16) with ECoG electrodes, recorded three-channel
recording. We used a portable microamplifier (Physiobelt) ECoG, and assessed spontaneous SWDs during baseline
to acquire the EEG signals and occasionally encountered and xylazine-induced SWDs. A substantial correlation was
signal disturbances due to incidental rat head movements. observed between the durations of spontaneous SWDs
These movements disrupt the physical contact between recorded during the 4-h interval at baseline and those of
the skin and the sensors, causing signal loss or zeroing. xylazine-induced SWDs measured at 6 min post-injection.
High-voltage sine waves were observed a few seconds after Here, we used the WAG/Rij rat genetic model of absence
the restoration of skin contact before commencing the epilepsy. 8-11 In contrast to chemical or electrical models of
acquisition of low-voltage electrical signals from the brain epilepsy, WAG/Rij rats exhibit spontaneous SWDs due to
(shown by “signal lost/noise” in Figure 6).
genetic predisposition. The PTZ model is one of the most
Three distinct epileptic phenotypes with varying degrees widely used chemical models of epilepsy. It provides a
of severity were identified based on the presence of SWDs simple and widely applicable method for studying epilepsy
during the 6-min post-injection intervals (Figure 6). This mechanisms and screening potential antiepileptic drugs;
classification was exclusively based on the EEG results, however, it is not a model of absence epilepsy. PTZ is one
excluding any additional behavioral assessments. of the first proconvulsant drugs used in animal models
(1) Asymptomatic rats did not exhibit 8 – 10-Hz SWDs, to induce seizure activity. 36-39 Injections of PTZ primarily
despite the presence of abnormalities, including brief induce tonic-clonic seizures rather than absence seizures.
6-Hz SWDs and occasional spike-wave complexes PTZ acts as a GABA-A receptor antagonist, suppressing
(Figure 6A). inhibitory synaptic function and leading to increased
(2) Mild epilepsy. Typical 8 – 10-Hz SWDs with a neuronal excitability. A single high-dose injection of
38
duration not exceeding 10 s occurring 2 – 8 times/6- PTZ (above 48 mg/kg) can induce acute, severe seizures.
min interval (Figure 6B). Chemical kindling, which induces repetitive seizures,
(3) Severe epilepsy. Frequent and prolonged 8 – 10-Hz can result from repetitive low-dose administrations
SWDs, some of which could last up to several (30 – 35 mg/kg) over time. 36,39 The WAG/Rij rat model is a

Volume 3 Issue 4 (2024) 7 doi: 10.36922/an.4464