Unilateral intrahippocampal injection of
kainic acid in adult mice reproduces most of the morphological characteristics of
hippocampal sclerosis (neuronal loss,
gliosis, reorganization of
neurotransmitter receptors, mossy fiber sprouting, granule cell dispersion) observed in patients with
temporal lobe epilepsy. Whereas some neuronal loss is observed immediately after the initial
status epilepticus induced by
kainate treatment, most reorganization processes develop progressively over a period of several weeks. The aim of this study was to characterize the evolution of seizure activity in this model and to assess its pharmacological reactivity to classical
antiepileptic drugs. Intrahippocampal electroencephalographic recordings showed three distinct phases of paroxystic activity following unilateral injection of
kainic acid (1 nmol in 50 nl) into the dorsal hippocampus of adult mice: (i) a
non-convulsive status epilepticus, (ii) a latent phase lasting approximately 2 weeks, during which no organized activity was recorded, and (iii) a phase of chronic seizure activity with recurrent hippocampal paroxysmal discharges characterized by high amplitude sharp wave onset. These recurrent
seizures were first seen about 2 weeks post-injection. They were limited to the injected area and were not observed in the cerebral cortex, contralateral hippocampus or ipsilateral amygdala. Secondary propagation to the contralateral hippocampus and to the cerebral cortex was rare. In addition hippocampal paroxysmal discharges were not responsive to acute
carbamazepine,
phenytoin, or
valproate treatment, but could be suppressed by
diazepam. Our data further validate intrahippocampal injection of
kainate in mice as a model of
temporal lobe epilepsy and suggest that synaptic reorganization in the lesioned hippocampus is necessary for the development of organized recurrent
seizures.