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Advanced Neurology                                                Non-invasive electroencephalography in rats




















            Figure 7. Schematic representation of the results of xylazine-based electroencephalography examinations in the second group of rats aged 5 – 15 months
            (n = 65). Each dot denotes one subject. Subjects that were evaluated at various ages are indicated by dots that are connected by lines.

            Table 1. Comparison between the genetic WAG/Rij rat model and the pharmacological PTZ model of epilepsy 6,9,11,23,36,38
                                                    WAG/Rij                               PTZ
            Nature of the models    Genetic model; absence seizures appear spontaneously   Chemical model; seizures are induced by the
                                                                          administration of PTZ
            Basic mechanisms        Cortico-thalamo-cortical circuitry and genetic factors  Acute seizure mechanisms
            Validity of the models  High face, predictive, and construct validity  Lower validity compared with the genetic models
            Durability of the models  Long-term studies, chronic absence epilepsy  Acute studies
            Clinical relevance of the models  Similar to human absence epilepsy in terms of clinical   Less representative of human absence epilepsy
                                    presentation and EEG features
            Mechanisms studied by the models  Spontaneous seizures and their underlying pathophysiology Acute mechanisms of seizure induction
            Model use: drug screening  Can be used for drug screening and may offer more   Can be used for drug screening
                                    predictive results
            Abbreviations: EEG: Electroencephalogram; PTZ: Pentylenetetrazol; WAG/Rij: Wistar Albino Glaxo from Rijswijk.

            the broad spectrum of manifestations associated with   them, 42% did not exhibit any symptoms of absence
            absence epilepsy. 42,43  In the present study, we identified   epilepsy. The severity of absence epilepsy increased with
            three epileptic phenotypes in the WAG/Rij rats. This   age in 23% of the rats, remained constant in 35% of them,
            heterogeneity contradicts the well-accepted homogeneity   and never decreased in severity in any of the rats. It is well
            of seizure severity in WAG/Rij rats. We hypothesize that   known that the incidence and duration of SWDs in WAG/
            the phenotypic variability of absence epilepsy in a cohort   Rij rats increases with age. 8,9,11,32,34  Our findings indicate
            of genetically prone WAG/Rij rats in the Institute of Higher   that 23% of the rats exhibited an age-related increase in
            Nervous  Activity  and  Neurophysiology  RAS  (Moscow,   the severity of absence epilepsy. In our model, the severity
            Russia) is comparable to the phenotypic variability of this   of absence epilepsy is empirically measured as a complex
            disease in human patients.                         characteristic that incorporates both the duration and
              The phenotypic variability of absence epilepsy in inbred   the number of SWDs that manifested following xylazine
            WAG/Rij rats highlights the necessity for developing non-  administration.
            invasive technologies that enable rapid diagnosis of absence   Our findings revealed that during the 6-minute
            epilepsy. It also implies the necessity for a personalized,   post-injection period, xylazine-induced SWDs closely
            subject-specific approach to rat models, considering their   resembled spontaneous SWDs in terms of spike-wave
            behavioral features and neurobehavioral comorbidities. 22  morphology and frequency. Subsequently, the 8–10-Hz

              The proposed technique is quick, secure, cost-effective,   SWDs gradually transitioned into 6-Hz SWDs, occasional
            and yields consistent outcomes. Importantly, it could   spike-wave complexes, and eventually into a slow-wave
            be conducted repeatedly throughout a rat’s lifespan to   activity that characterizes a sedative state. Notably,
            evaluate the age-related progression of absence epilepsy. In   xylazine did not elicit pronounced 8 – 10-Hz SWDs in
            our investigation, 26 rats were subjected to repetitive EEG   asymptomatic rats; however, it induced brief 6-Hz SWDs
            examinations at ages ranging from 5 to 15 months. Among   and occasional spike-wave complexes. Alterations in the


            Volume 3 Issue 4 (2024)                         9                                doi: 10.36922/an.4464
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