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Abstract <p>Epilepsy is a severe neurological disorder, with approximately30% of patients exhibiting therapy resistance. The lithium-pilocarpinemodel of temporal lobe epilepsy (TLE) in rats reproduces key featuresof the disease, but long-term monitoring of spontaneous seizuresis time-consuming and labor-intensive, necessitating the searchfor additional biomarkers of epileptogenesis. In clinical practice, EEG—particularlythe analysis of interictal epileptiform patterns—plays a crucialrole in epilepsy diagnosis. Provocative tests (sleep deprivation,photic stimulation, etc.) enhance the detection of pathologicalpatterns. In experimental settings, a similar effect can be achievedusing low doses of convulsants, such as pentylenetetrazol (PTZ),though such methods are rarely employed. The aim of this study wasto investigate the effect of low-dose PTZ on epileptiform activityin the lithium-pilocarpine TLE model in rats and compare this methodwith maximal electroshock (MES) testing. The TLE model was inducedin male Wistar rats (experimental group: pilocarpine following LiClpretreatment; control group: saline). Six months after the developmentof spontaneous recurrent seizures, EEG electrodes were implantedonto the skull surface. EEG recordings were conducted in two phases:baseline and following PTZ administration (40 mg/kg). Three weekslater, seizure susceptibility was assessed using MES. The resultsshowed that baseline EEG recordings revealed no differences betweenthe groups. However, after PTZ administration, a clear distinctionwas observed: Control rats exhibited regular bursts of high-amplitudesharp waves (4–8 Hz), whereas rats with the epilepsy model predominantly displayedinterictal spikes and spike-wave complexes. In contrast, MES testingrevealed no differences in the threshold currents for inducing hindlimbextension between control and experimental rats. Thus, the provocativetest using low-dose PTZ is a highly sensitive method for detectingepileptiform activity in the TLE model, providing greater diagnosticvalue than MES testing. These findings support the potential of thisapproach for preclinical research.</p>

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Response Characteristics to Pentylenetetrazol Administration in Rats with the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy

  • 期刊论文

  • 发表日期：

    2025年7月1日

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  • M. R. Subkhankulov,
  • O. E. Zubareva

摘要

Abstract

Epilepsy is a severe neurological disorder, with approximately30% of patients exhibiting therapy resistance. The lithium-pilocarpinemodel of temporal lobe epilepsy (TLE) in rats reproduces key featuresof the disease, but long-term monitoring of spontaneous seizuresis time-consuming and labor-intensive, necessitating the searchfor additional biomarkers of epileptogenesis. In clinical practice, EEG—particularlythe analysis of interictal epileptiform patterns—plays a crucialrole in epilepsy diagnosis. Provocative tests (sleep deprivation,photic stimulation, etc.) enhance the detection of pathologicalpatterns. In experimental settings, a similar effect can be achievedusing low doses of convulsants, such as pentylenetetrazol (PTZ),though such methods are rarely employed. The aim of this study wasto investigate the effect of low-dose PTZ on epileptiform activityin the lithium-pilocarpine TLE model in rats and compare this methodwith maximal electroshock (MES) testing. The TLE model was inducedin male Wistar rats (experimental group: pilocarpine following LiClpretreatment; control group: saline). Six months after the developmentof spontaneous recurrent seizures, EEG electrodes were implantedonto the skull surface. EEG recordings were conducted in two phases:baseline and following PTZ administration (40 mg/kg). Three weekslater, seizure susceptibility was assessed using MES. The resultsshowed that baseline EEG recordings revealed no differences betweenthe groups. However, after PTZ administration, a clear distinctionwas observed: Control rats exhibited regular bursts of high-amplitudesharp waves (4–8 Hz), whereas rats with the epilepsy model predominantly displayedinterictal spikes and spike-wave complexes. In contrast, MES testingrevealed no differences in the threshold currents for inducing hindlimbextension between control and experimental rats. Thus, the provocativetest using low-dose PTZ is a highly sensitive method for detectingepileptiform activity in the TLE model, providing greater diagnosticvalue than MES testing. These findings support the potential of thisapproach for preclinical research.