Brainstem activity, apnea, and death during seizures induced by intrahippocampal kainic acid in anaesthetized rats (original) (raw)
THE ROLE OF EPILEPTIC ACTIVITY IN HIPPOCAMPAL AND 'REMOTE' CEREBRAL LESIONS INDUCED BY KAINIC ACID
Kainic acid (KA) was injected systemically, intracerebroventricularly (i.c.v.) and focally in the amygdala and other deep brain structures in the rat. EEG and behavioral changes were studied in relation to the neuropathology which developed subsequently. Following intra-amygdaloid KA injection, diazepam blocked the epileptic events induced by the toxin, and abolished the neuronal loss usually seen in the lateral septum, claustrum, and contralateral cortex and hippocampus. The lesions in medial thalamic structures and ipsilateral hippocampus were also reduced by diazepam. Prior transection of the perforant path ipsilateral to the KA injection also decreased the severity of the electrographic and motor effects of the toxin and similarly reduced the extent of distant ('remote') pathological brain damage. Neither diazepam nor perforant path transection reduced the damage at the site of KA injection. Kainic acid (0.4-2/~g) injected into the bed nucleus of the stria terminalis (BST) or the medial septum produced seizures with a longer latency and little brain damage outside the injection site. In contrast, intrastriatal KA injections were followed by ipsilateral hippocampal lesions. i.c.v. Injection of KA (0.4-1.6/zg) produced a complex syndrome which included bilateral exophthalmos, mydriasis, foaming, tremor of the vibrissae, and paw and body tremor. The pattern of brain damage resembled that seen following intraamygdaloid administration of the toxin. In addition, however, there was a bilateral necrosis of the pyriform and prepyriform cortices up to the rhinal fissure. Systemic administration of diazepam (i.p.) reduced the extent of the damage and in particular completely prevented the cortical damage.
Brain Research, 1980
Intrastriatal injectmns of kainic acid m rats acutely induced repeated episodes of clonic convulsions. Spontaneously recurrent generahzed seizures and a potentlanon of the convulsant effects of pentylenetetrazol were then observed in most of the m lected rats several weeks after surgery. In additmn to marked loss of strmtal neurons, llmbic pathological alterations similar to those found in human temporal lobe epilepsy were observed in the brains of the kainic-acid treated rats. It is proposed that this preparation might serve as an animal model of human temporal lobe epilepsy.
The maturation of the seizure/brain damage syndrome produced by parenteral administration of kainate was studied in the rat. The motor, electrographic and metabolic alterations are described in the present report, the maturation of the pathological abnormalities and of the specific kainate binding sites are described in the two following companion papers. Parenteral kainate produces tonico-clonic seizures until the end of the third week of age when limbic motor signs (wet-dog shakes, facial myoclonia, paw tremor etc.) were first produced. Using the 2-deoxyglucose autoradiographic method, we found that in animals of 3 days of age and until the third week of age, kainate produced a rise in metabolism restricted to the hippocampus and lateral septum. This was paralleled by paroxysmal discharges which were recorded in the hippocampus. Starting from the end of the third week of age approximately-i.e. when the toxin produced limbic motor seizures-there was a rise of labelling in other structures which are part of or closely associated to the limbic system i.e. the amygdaloid complex, the mediodorsal and adjacent thalamic nuclei, piriform. entorhinal and rostra1 limbic cortices and areas of projection of the fornix. These metabolic maps are thus similar to those seen in adults. Two main conclusions can be drawn from these experiments: (1) kainate activates the hippocampus from a very early age probably by means of specific receptors present in this structure and (2) the limbic syndrome will only be produced by the toxin once the limbic circuitry-including in particular the amygdaloid complex-is activated by the procedure i.e. after the third week of age.
The Journal of Neuroscience, 1984
Depression of GABA-mediated IPSPs has been proposed to be a crucial factor in the onset of epileptiform activity in most models of epilepsy. To test this idea, we studied epileptiform activity induced by bath application of the excitatory neurotoxin kainic acid (KA) in the rat hippocampal slice. Repetitive field potential firing, spontaneous or evoked, occurred during exposure to KA. Intracellular records from 52 CA1 pyramidal cells during changes from control saline to saline containing i PM KA indicated that KA depolarized cells an average of about 5 mV and caused a 15% decrease in input resistance. Action potentials and current-induced burst afterhyperpolarizations did not change significantly. In several cells the tonic effects of KA were preceded by a transient phase of sporadic, spontaneous depolarizations of 2 to 10 mV and 50 to 200 msec duration. These phasic depolarizations were blocked by hyperpolarization. The major effect of 1 PM KA was a depression of synaptic potentials. Initially, KA depressed fast GABA-mediated IPSPs and slow, non-GABA-mediated late hyperpolarizing potentials to 23% and 40% of control values, respectively. IPSP depression correlated closely with onset of burst potential firing in response to synaptic stimulation. Similar observations were made on six cells from the CA213 region, although these cells were affected by lower doses of KA. The mechanism of IPSP depression was studied by using KCl-filled electrodes to invert spontaneous IPSPs and make them readily visible. In nine CA1 cells the rate and amplitude of spontaneous IPSPs transiently increased but then decreased in conjunction with evoked IPSP depression. Possible KA effects on postsynaptic GABA responses were investigated by applying GABA locally to cells. KA did not significantly affect GABA responses. Prolonged exposure of CA1 cells to KA in doses of 1 PM or higher depressed intracellularly and extracellularly recorded EPSPs and all field potential activity. This depression was not apparently due to depolarization block in CAl, however. We conclude that KA induces epileptiform activity in hippocampus principally by a presynaptic block of IPSP pathways. Recent studies of epileptiform activity induced by bicuculline (Schwartzkroin and Prince, 1980), picrotoxin (Alger and Nicoll, 1980a), or penicillin (Wong and Prince, 1979; Dingledine and Gjerstad, 1980) in the in vitro hippocampal slice preparation have shown that reduction of pyramidal cell IPSPs is closely associated with the onset of repetitive cell firing and epileptiform extracellular field potential discharges. To test whether disinhibition is a necessary factor in generation of epi
The control of kainic acid-induced status epilepticus
Epilepsy Research, 2010
In the present study the effectiveness of different diazepam-ketamine combinations to control kainic acid-induced status epilepticus in rats was evaluated. We show that electrographic monitoring is mandatory to enable reliable assessment of status epilepticus control as the number of false positives is extremely high when status epilepticus control is only behaviourally assessed. Diazepam and ketamine synergistically blocked all electrographical seizure activity.
Neurological Sciences, 2009
Status epilepticus is common in infants and may have long-term consequences on the brain persisting into adulthood. Vascular ischemia is a common cause of stroke in adulthood. The extent of stroke in 15-day-old rats is larger when previously exposed to kainic acid-induced status epilepticus. In this paper, we assess whether shortening the duration of seizures modifies subsequent susceptibility to middle cerebral artery occlusion. We administered pentobarbital 50 mg/kg to abort seizures after 1 h. Although administration of pentobarbital aborted seizures, it had no effect on volume of infarction following ischemia. This study indicates that there is dissociation between stopping status epilepticus and modifying its long-term consequences.
Epilepsy Research, 2013
Status epilepticus (SE) is a dreaded neurological emergency. A reignited interest in SE has resulted in a more adaptive use of treatment protocols. More knowledge on SE of various aetiologies is therefore needed. We are interested in treatment of SE under hyponatremia, and have here evaluated whether SE induced by systemic kainic acid could be a suitable platform for such studies. Acute hyponatremia was induced in C57/BL6 mice by intraperitoneal injection of dDAVP and water loading. Hyponatremic mice displayed an increased frequency of epileptiform spikes on EEG and 5/9 hyponatremic mice displayed electrographic seizures. After kainic acid (20 mg/kg) treatment, hyponatremic mice displayed significantly longer time with electrographic seizure activity, which was also seen after treatment with diazepam (20 mg/kg). We conclude that hyponatremia augments kainic acid-induced SE, This model might be a valuable platform for studies on treatment of SE in hyponatremia.
Epilepsy Research, 1992
Clinical and experimental data suggest that the role of corpus callosum in epilepsy includes synchronization, spread, excitation and inhibition. Section of the corpus callosum (SCC) is known to be a useful therapy in selected types of generalized epilepsy, i.e., tonic, atonic and generalized convulsive seizures, but not partial seizures which may be exacerbated by this procedure. The goal of this study was to determine the effect of SCC in the kainic acid (KA) model of limbic se.ixures in rata. Using several doses of KA (2.5,s and 10 mg/kg) injected systemically, we found a potentiation of the behavioral, electrographic and histological effects of KA in the SCC group of animals compared to the sham-operated control rats. A low dose of kainic acid (2.5 and 5 mg/kg) induced status epilepticus in the SCC animals, but not in the sham-operated control rats. These data demonstrate that in the KA model of temporal lobe seizures, SCC not only fails to protect, but actually intensifies seixures. This finding is compatible with the hypothesis that there is an inhibitory influence, via the corpus callosum, of the non epileptic neocortex on its contralateral homologue in the kainic acid model.