Recurrent seizures and hippocampal sclerosis following intrahippocampal kainate injection in adult mice: electroencephalography, histopathology and synaptic reorganization similar to mesial temporal lobe epilepsy
Section snippets
Animals and surgical procedures
Experiments were performed on 83 adult male Swiss mice (CERJ, Le-Genest-St-Isle, France) weighing about 30–35 g housed in a 12 h light–dark controlled cycle with free access to food and water. All experiments were performed in accordance to the European Committee Council Directive of November 24, 1986 (86/69/EEC). Fifty-three mice were stereotaxically injected with kainate and 30 with saline into the right dorsal hippocampus (coordinates from bregma: A=−1.8 mm and L=−1.6 mm, from brain surface:
Electroencephalographic and behavioural consequences of intrahippocampal kainate injection
Saline injection did not induce any change in EEG patterns. Following kainate administration and during awakening from surgery, the mice were immobile most of the time and presented intermittent contraversive clonic deviations of the head and chewing. Some mice displayed rotations contraversive to the site of kainate injection. EEG recordings revealed continuous or subcontinuous 2–5 Hz polyspike-and-waves in the ipsilateral cortex (Fig. 1B). This phase lasted for up to 5 h. Clonic deviations of
Discussion
Our findings provide evidence suggesting that the long-term EEG, behavioural, metabolic and histological consequences of intrahippocampal injection of kainate in mice are very similar to human MTLE.
Conclusions
Intrahippocampal kainate injection in adult mice appears to be a promising new model of human MTLE. The validity of this model relies on several behavioural and pathological features. In particular, the histological sequelae are similar to the hippocampal sclerosis described in human MTLE, particularly cell loss in the hilus and hippocampal neuronal cell layers including the more vulnerable site CA1, granule cell dispersion, astrogliosis and mossy fibre sprouting. Likewise, recurrent partial
Acknowledgements
The authors wish to thank Jean-Marc Fritschy for helpful comments. V.B. was the recipient of a grant from LAFON Laboratories and the French Collège des Enseignants de Neurologie.
References (69)
- et al.
Synaptic reorganization by mossy fibers in human epileptic fascia dentata
Neuroscience
(1991) - et al.
Firing pattern of human limbic neurons during stereoencephalography (SEEG) and clinical temporal lobe seizures
Electroenceph. clin. Neurophysiol.
(1987) Limbic seizures and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy
Neuroscience
(1985)- et al.
The role of epileptic activity in hippocampal and “remote” cerebral lesions induced by kainic acid
Brain Res.
(1980) - et al.
Evidence suggesting secondary epileptogenic lesions after kainic acid: pretreatment with diazepam reduces distant but not local brain damage
Brain Res.
(1979) - et al.
Long-term effects of intrahippocampal kainic acid injection in rats: a method for inducing spontaneous recurrent seizures
Electroenceph. clin. Neurophysiol.
(1982) - et al.
Progressive neuronal loss induced by kindling: a possible mechanism for mossy fiber reorganization and hippocampal sclerosis
Brain Res.
(1990) - et al.
Sprouting of GABAergic and mossy fiber axons in the dentate gyrus following intrahippocampal kainate in the rat
Expl Neurol.
(1990) - et al.
Hippocampal interneuron loss and plasticity in human temporal lobe epilepsy
Brain Res.
(1989) Mesial temporal (Ammon's horn) sclerosis as a common cause of epilepsy. Aetiology, treatment and prevention
Lancet
(1974)
A permanent change in brain function resulting from daily electrical stimulation
Expl Neurol.
Astrocytes in kindling; revelance to epileptogenesis
Epilepsy Res.
Effects of anaesthesics, anticonvulsivants and glutamate antagonists on kainic acid-induced local and distal neuronal loss
J. neurol. Sci.
Blockage of pilocarpine- or kainate-induced mossy fiber sprouting by cycloheximide does not prevent subsequent epileptogenesis in rats
Neurosci. Lett.
Kainic acid-induced limbic motor seizures: metabolic, behavioral, electroencephalographic and neuropathological correlates
Brain Res.
Possible mechanisms inducing granule cell dispersion in humans with temporal lobe epilepsy
Epilepsy Res.
Delayed cell death in the contralateral hippocampus following kainate injection into the CA3 subfield
Neuroscience
Hippocampal plasticity in the kindling model of epilepsy in rats
Neurosci. Lett.
Widespread patterns of neuronal damage following systemic or intracerebral injections of kainic acid: histological study
Neuroscience
A simplified Timm staining procedure compatible with formaldehyde fixation and routine paraffin embedding of rat brain
Brain Res. Bull.
Kainic acid induced seizures: neurochemical and histopathological changes
Neuroscience
Repeated seizures increase GFAP and vimentin in the hippocampus
Brain Res.
Bilateral reorganisation of mossy fibres in the rat hippocampus after a unilateral intracerebroventricular kainic acid injection
Brain Res.
Morphogenetic effect of kainate on adult hippocampal neurons associated with a prolonged expression of brain-derived neurotrophic factor
Neuroscience
Electroclinical features of kainic acid induced status epilepticus in freely moving rats. Microinjection into the dorsal hippocampus
Electroenceph. clin. Neurophysiol.
Limbic seizures produced by pilocarpine in rats: behavioural, electroencephalographic and neuropathological study
Behav. Brain Res.
Temporal lobe volumetric cell densities in temporal lobe epilepsy
Epilepsia
Recurrent excitatory circuits by “sprouted” mossy fibers into the fascia dentata of human hippocampal epilepsy
Epilepsia
Kainic acid induced hippocampal seizures in the rats: comparisons of acute and chronic seizures using intrahippocampal versus systemic injections
Ital. J. neurol. Sci.
The ontogeny of seizures in rat model of limbic epilepsy: evidence for a kindling process in the development of chronic spontaneous seizures
Brain Res.
An immunohistochemical investigation with monoclonal antibodies to somatostatin
Histochemistry
Neuron loss, granule cell axon reorganization, and functional changes in the dentate gyrus of epileptic kainate-treated rats
J. comp. Neurol.
The pilocarpine model of epilepsy
Ital. J. neurol. Sci.
Cited by (0)
- 1
Present address: Laboratoire de Neurobiologie et Neuro-imagerie Expérimentales, Université Victor Ségalen, Bordeaux, France.