Background: There is no universally accepted behavioral scoring to define the early development of pentylenetetrazole (PTZ) kindling. Therefore, studies investigating alterations of neurogenesis in the PTZ model were mainly focused on full kindled animals rather than early stages of kindling. This study aimed to determine an appropriate behavioral index for categorizing stages of PTZ kindling progress and to evaluate neurogenesis during PTZ kindling. Materials and Methods: Twenty-four mice were intraperitoneally injected with a sub-convulsive dose of PTZ (40mg/kg) every other day until they became full kindled. The first occurrence of different seizure behaviors and their durations were recorded during kindling development, and the different stages of kindling were categorized. Neurogenesis was evaluated in the lateral subventricular zone (SVZ) at each stage of kindling by immunofluorescence staining. Results: First occurrence of restlessness, motionless staring, hind limb tonic extension, Straub’ s tail, myoclonic jerk, and tonic-clonic were sequentially observed in more than 80% of animals with increasing PTZ injections. The duration of the myoclonic jerk was significantly longer than the other seizure behaviors. The significantly higher percentage of BrdU-positive cells was found in SVZ of mice showing tonic-clonic in comparison to other seizure behaviors. Conclusion: A hierarchy behavior was observed during the kindling process when considering the first occurrence of seizure behaviors. We defined the first occurrence of restlessness, motionless, hind limb tonic extension and Straub’ s tail behaviors as an early phase, myoclonic jerk as a borderline phase and tonicclonic as a late phase of PTZ-induced kindling. Our results indicated an enhanced SVZ neurogenesis at the late phase of kindling.

Vitamin A and its derivatives have recently reported to be implicated in synaptic plasticity. The possible effect of vitamin A and its precursor, b-carotene, on seizure acquisition was tested in PTZ kindling model of epilepsy. Vitamin A and b-carotene were tested for their ability to 1) suppress seizures (clonic and tonic) and lethality induced by PTZ in PTZ-kindled mice (anticonvulsant effect) and 2) attenuate the development of sensitization to convulsive and lethal effects of PTZ in kindled mice (anti-epileptogenic effect) when given as a pretreatment prior to each PTZ injection during kindling acquisition. Diazepam was used as positive control group. All these drugs showed anti-epileptogenic effects against PTZ-induced tonic seizures and lethality. Vitamin A and b-carotene had no effect on clonic seizures induced by PTZ in kindled mice. It can be concluded that vitamin A and b-carotene possess anti-epileptogenic activity. Retinoids appear to be valuable for development of a new class of anticonvulsant drugs.