PTZ-induced seizures in mice require a revised Racine scale

Abstract

Seizure severity in experimental models of epilepsy is often evaluated by means of the Racine scale, in spite of the use of seizure induction methods that are different from those of the original paper by Racine in 1972. In such cases, the use of this scale is not always justified because some seizure behaviors are significantly different from those originally described or not present at all. Correspondingly, the pentylenetetrazole (PTZ) model, which is frequently used for antiepileptic drug research, lacked an adequate assessment tool to measure seizure severity. In 2009, an adapted intensity scale for PTZ-induced seizures was already designed for rats. Here, we evaluated electroencephalographic (EEG) and behavioral parameters after a single PTZ injection, to determine whether this scale is also suitable for use in mouse studies. We found that the scale designed for rats is quite robust and can thus be applied to score seizure severity in mice. Yet, certain convulsive behaviors and EEG characteristics were distinct between species. Therefore, a species-specific scale was designed, which included the concomitant EEG characteristic next to the behavioral expressions we observed, in order to establish a userfriendly scoring scale for PTZ-induced seizures in mice. To evaluate applicability, we utilized the scale in a seizure susceptibility study of a transgenic mouse model. We demonstrated that the maximum severity scores obtained with the newly revised Racine scale highly correlated with the administered dose. Hence, the revised scale differentiates well between different classes of seizure severity.

Diverged morphology changes of astrocytic and neuronal primary cilia under reactive insults

“…All mice were returned to their home cage after observation. A modified Racine scale was used to quantify seizure severity [36,37]: 0, no change in behavior; 1, repetitive chewing; 2, head bobbing; 3, involuntary movement of forelimbs with tremors; 4, involuntary movement of all limbs with rearing and falling; and 5, hypertonia, loss of movement, and death.…”

Characterization of seizure susceptibility in Pcdh19 mice

“…Digitized data were acquired and analyzed with Sirenia software (Pinnacle Technology) along with contemporaneous video recordings. Epileptiform activity was scored manually offline by a reviewer blinded to gender and genotype, according to a revised Racine scale 12 as follows: −1, normal baseline; 0, whisker trembling; 1, sudden behavioral arrest; 2, facial jerking; 3, myoclonic jerks; 4, clonic seizure (CS) sitting; 5, clonic, tonic-clonic seizure, lying on belly; 6, clonic, tonic-clonic seizure with loss of posture and wild jumping; 7, tonic extension, possibly leading to respiratory arrest and death.…”

Home-cage Monitoring Ascertains Signatures of Ictal and Interictal Behavior In Mouse Models of Generalized Seizures

“…The first objective was to apply home-cage monitoring to study seizure severity, an endophenotype central to rodent studies designed to demonstrate pharmacologically/genetically mediated alleviations or exacerbations of seizure severity. In studies that employ PTZ induction, seizure severity has often been equated with convulsive severity: ordinal scales designed to quantify seizure severity assign low scores to hypoactivity/immobility (assessed empirically), intermediate scores to myoclonic seizures (which are often subtle), and high scores to convulsive or maximal 20 seizures, often with even higher scores for seizures associated with death (15,16,19,22). Our data showed that in the first 30 minutes, PTZ-treated mice (compared with saline) displayed profound immobility and a significant sheltering deficit.…”

“…These seizures recapitulate the semiology, electroencephalographic characteristics (17) and pharmacological responsiveness (18) of seizures with a generalized onset. Differences in seizure severity are deduced from (i) subjectively scored ordinal scales of convulsive severity (e.g., Racine scale) that are inconsistently applied (19)(20)(21)(22), (ii) measures of convulsion latency or duration (17,18), and/or (iii) rates of frank seizure-induced mortality (11). These measures are based on the assumption that more severe seizures in mice are those that are convulsive and/or lethal, arise with a shorter latency and/or are of longer duration.…”