Kainic Acid-induced Epilepsy Research Articles

Upregulation of L-Type Ca2+Channels in Reactive Astrocytes after Brain Injury, Hypomyelination, and Ischemia

Anti-peptide antibodies that specifically recognize the alpha1 subunit of class A-D voltage-gated Ca2+ channels and a monoclonal antibody (MANC-1) to the alpha2 subunit of L-type Ca2+ channels were used to investigate the distribution of these Ca2+ channel subtypes in neurons and glia in models of brain injury, including kainic acid-induced epilepsy in the hippocampus, mechanical and thermal lesions in the forebrain, hypomyelination in white matter, and ischemia. Immunostaining of the alpha2 subunit of L-type Ca2+ channels by the MANC-1 antibody was increased in reactive astrocytes in each of these forms of brain injury. The alpha1C subunits of class C L-type Ca2+ channels were upregulated in reactive astrocytes located in the affected regions in each of these models of brain injury, although staining for the alpha1 subunits of class D L-type, class A P/Q-type, and class B N-type Ca2+ channels did not change from patterns normally observed in control animals. In all of these models of brain injury, there was no apparent redistribution or upregulation of the voltage-gated Ca2+ channels in neurons. The upregulation of L-type Ca2+ channels in reactive astrocytes may contribute to the maintenance of ionic homeostasis in injured brain regions, enhance the release of neurotrophic agents to promote neuronal survival and differentiation, and/or enhance signaling in astrocytic networks in response to injury.

GABA A receptor subunits in the rat hippocampus III: altered messenger RNA expression in kainic acid-induced epilepsy

Kainic acid-induced seizures in rats represent an established animal model for human temporal lobe epilepsy. The neuropathological sequelae include acute status epilepticus followed by neurodegeneration in the CA1 and CA3 sector of the Ammon's horn and of interneurons in the hilus of the dentate gyrus. After about three weeks spontaneous recurrent seizures become manifest. We investigated changes in messenger RNA expression of 13 GABA A receptor subunits in the hippocampus of rats in the initial phase (6 h, 12 h and 24 h) after acute kainic acid-induced status epilepticus and seizure-related neuronal cell damage during and after acquisition of spontaneous recurrent seizures (seven and 30 days after kainic acid injection). In the granule cell layer, initial (after 6 to 12 h) decreases in ( α 2, α 3, α 5, β 1, β 3, γ 2 and δ messenger RNAs (by about 25 to 50%) were accompanied by increases (by about 50%) in α 1, α 4, and β 2 messages. At later intervals (after seven to 30 days), expression of α 2, α 4, β 3 and γ 2 messenger RNAs recovered to control values, with α 5 and δ messenger RNA still being reduced (by 15 and 40% below control levels, respectively). Concentrations of the transcripts encoding for α 1, α 3, β 1, β 2, became markedly enhanced (between 20 and 50% of controls). Within the pyramidal cell layers CA1 and CA3, decreases in α 2, α 4, α 5, β 1–3 and γ 2 messenger RNAs were detected after seven to 30 days, reflecting pronounced neurodegeneration in these areas. The α 1 transcript was decreased in CA3 after 24 h and increased to control levels indicating compensatory up-regulation of this message after seven days. Messenger RNAs encoding for α 3-, γ 1-, and γ 3-subunits were detected at rather low levels, α 6 was not present in the hippocampus. Our data suggest a fast but transient change in the expression of messenger RNAs encoding for different subunits of the GABA A receptor in the granule cell layer of the dentate gyrus. This is followed by a lasting augmentation of messenger RNAs encoding different GABA A receptor subunits in the same cell layer indicating long-lasting GABAergic inhibition. Changes within the pyramidal cell layer are mostly determined by concomitant neurodegenerative processes.

Altered expression of NPY-Y 1 receptors in kainic acid induced epilepsy in rats

Kainic acid-induced limbic seizures cause lasting increases in neuropeptide Y (NPY) expression in hippocampal granule cells/mossy fibers. The expression of NPY-Y 1 receptors in these neurons were investigated, using in situ hybridization for Y 1 mRNA and receptor autoradiography with the Y 1-specific ligand [ 125I][Pro 34]PYY. Six hours after kainic acid-induced seizures, Y 1 receptor mRNA levels decreased by 80% in granule cells and concomitantly increased (by 75%) in CA2 pyramidal neurons. Subsequently, persistent decreases in Y 1 mRNA were seen, both in the stratum granulosum and in CA2. Changes in mRNA concentrations were accompanied by a transient, although non-significant, increase in [ 125I][Pro 34]PYY binding in the molecular layer of the dentate gyrus after 4–6 h which was succeeded by a lasting decrease in binding which indicates a persistent down-regulation of Y 1 receptors in hippocampal areas in kainic acid-induced epilepsy.

Differential responses of neurokinin A, neuropeptide Y and calcitonin gene-related peptide in kainic acid-induced epilepsy in the rat

Differential responses of neurokinin A, neuropeptide Y and calcitonin gene-related peptide in kainic acid-induced epilepsy in the rat

Effect of mannitol treatment on brain neurotransmitter markers in kainic acid-induced epilepsy

The effect of mannitol treatment on the behavioural, morphological and neurochemical brain damage induced after subcutaneously applied kainic acid (10 mg/kg) was studied in the rat. Mannitol at a dose of 1.5 g/kg was injected intravenously 10 min, 1.5 h and 3 h respectively after kainic acid administration. A protective effect of mannitol was observed only when mannitol was given 1.5 h after kainic acid application i.e. within the early phase of kainic acid-induced brain oedema development. At this time period, mannitol prevented the development of kainic acid-induced seizures as well as irreversible brain lesions and neurochemical changes, the latter being reduction of noradrenaline levels in amygdala/ pyriform cortex measured 3 h, and reduction of glutamate decarboxylase and choline acetyltransferase activities measured 3 days after kainic acid treatment. Similarly loss of glutamate decarboxylase activity in dorsal hippocampus induced by kainic acid was prevented by mannitol treatment. It is concluded that by washing out brain oedema, mannitol treatment may prevent propagation of seizures and brain damage in the kainic acid model of epilepsy.