Biomedical subjects

E Huisman

Publications and source records attributed to E Huisman.

7 recordsLinked to original sources

PubMed1991

Chronic neonatal MK-801 administration leads to a long-lasting increase in seizure sensitivity during the early stages of hippocampal kindling.

Persistent effects of chronic neonatal administration of the N-methyl-D-aspartate (NMDA) antagonist MK-801 were investigated by measuring susceptibility to CA1 kindling epileptogenesis in adulthood. Rat pups were chronically treated with MK-801 from postnatal day 8 through day 19. Hippocampal kindling showed an increase in electrical seizure duration in the MK-801-treated group as compared with controls along with a more severe expression of behavioral seizures during the first few kindling stimulations. These results show that neonatal interference with NMDA receptor function leads to a long-lasting increase in hippocampal excitability.

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PubMed1991

Development of changes in endogenous GABA release during kindling epileptogenesis in rat hippocampus.

The calcium-dependent gamma-aminobutyric acid (GABA) and glutamate release from rat hippocampal CA1 slices, evoked by a 1-min depolarization with 50 mM K+, was investigated in different stages of kindling epileptogenesis. Kindling was induced by tetanic stimulation of the Schaffer collateral/commissural pathway. In agreement with our previous results, we found a significantly increased calcium-dependent GABA release compared to that of implanted controls, in a group of fully kindled animals 1 day after the last seizure and also 25-36 days after the last seizure. In addition, we found that the increase in GABA release was associated with late phases of kindling epileptogenesis since no significant alterations were found in partly kindled animals that had received only 6 kindling stimulations while a significant increase was apparent in animals that had received 14 tetanic stimuli. When the release protocol was carried out in the presence of SK&F 89776-A, a blocker of the GABA uptake carrier, an additional amount of GABA was found after depolarization. This additional amount of GABA, reflecting the amount of GABA taken up under conditions without blocker, was in kindled animals not different from controls which demonstrates that a reduced GABA uptake does not account for the observed enhanced release in kindled animals. The calcium-dependent release of glutamate evoked by 1 min of high potassium depolarization was not significantly changed in the kindled groups. Only after prolonged depolarization during 4 subsequent minutes a significant increase in animals of the fully kindled group and at long-term after kindling was observed. The threshold K+ concentration for eliciting a calcium-dependent release of GABA and glutamate, was not changed in the kindled animals.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1990

Neonatal clonidine treatment results in long-lasting changes in noradrenaline sensitivity and kindling epileptogenesis.

In the present experiment we tested the hypothesis that early interference with noradrenaline transmission can have permanent consequences for brain function in adulthood. Neonatal depletion of noradrenaline by daily subcutaneous injections of clonidine results in supersensitivity to noradrenaline in adult hippocampal CA1 cells as shown in our previous microiontophoretic study. These findings were confirmed and extended here with dose-response curves. Furthermore, we tested whether this form of neonatal interference with noradrenaline also permanently affects long-lasting plasticity as revealed in kindling epileptogenesis in adulthood. The initiation of the epileptic activity after the kindling stimulation was significantly delayed in the clonidine-treated group, and all measured parameters of seizure expression tended to be retarded in comparison with saline-treated control rats. This indicates that noradrenaline supersensitivity induced by neonatal clonidine treatment retards kindling development in adulthood.

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PubMed1990

Kindling increases the K(+)-evoked Ca2(+)-dependent release of endogenous GABA in area CA1 of rat hippocampus.

The release of endogenous amino acids from hippocampal CA1 subslices under basal conditions and the release evoked by high potassium (50 mM K+) depolarization was studied during kindling epileptogenesis. Emphasis was put on the release of the amino acid neurotransmitters gamma-aminobutyric acid (GABA) and glutamate. Kindling was induced by tetanic stimulation of the Schaffer-collaterals/commissural fibers of the dorsal hippocampus of the rat. The calcium-dependent GABA release in the presence of high K+ was significantly increased (40-46%) in fully kindled animals, 24 h after the last seizure, in comparison to controls. At long-term, 28 days after the last seizure, the calcium-dependent GABA release was still significantly increased (45-49%). An increased release of GABA in kindled animals was still found when GABA uptake was blocked by nipecotic acid. In contrast, no significant alterations were encountered in the basal or high potassium induced release of the excitatory amino acids aspartate and glutamate. These results suggest that kindling epileptogenesis is accompanied by a specific and long-lasting enhancement of GABA exocytosis which may lead to a desensitization of the GABA receptor, and thus determine the increase of seizure sensitivity.

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PubMed1989

Kindling induced changes in parvalbumin immunoreactivity in rat hippocampus and its relation to long-term decrease in GABA-immunoreactivity.

The immunoreactivity of parvalbumin (PV), a Ca2+-binding protein present in a subpopulation of interneurons, was studied in the hippocampal CA1 region during kindling epileptogenesis, induced by tetanic stimulation of the Schaffer collateral/commissural fibers. PV-immunoreactivity was increased in comparison to controls after 13 afterdischarges and after the induction of generalized seizures. A quantification of the number of PV-immunoreactive somata showed an increase of 20% in both stages of kindling. This level had returned to baseline level 31 days after the last seizure. These results imply that changes in PV-immunoreactivity are related to seizure activity rather than to the long-term increase in seizure sensitivity in kindled animals. Co-localization study in controls showed that 32% of PV-immunoreactive somata were also immunopositive for GABA. A colocalization study in stratum oriens and pyramidale on the stimulated side of kindled animals 31 days after the last generalized seizure showed neither a reduction in the number of PV-immunoreactive somata nor in the number of GABA-immunopositive cell bodies that co-localized with PV. In contrast, the number of GABA-immunoreactive somata that did not co-localize with PV was reduced by 50%. It has been shown that a large influx of Ca2+ plays a crucial role in epileptogenesis. Here we demonstrate that the presence of the calcium-binding protein parvalbumin seems to exert a protective effect against the process that leads to a decrease in GABA content.

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PubMed1989

Decrease in GABA immunoreactivity and alteration of GABA metabolism after kindling in the rat hippocampus.

The kindling model of epilepsy, induced by tetanic stimulation of Schaffer collateral/commisural fibers, was studied in the rat hippocampus. Gamma-aminobutyric acid immunoreactivity was used to quantify the number of GABA-immunoreactive somata per mm2 in CA1 region, 28 days after the last generalized seizure. Comparison of the numbers obtained from kindled animals with those from controls, showed a significant decrease (18%) on the ipsilateral stimulated side but none on the contralateral side. In control rats injection of the GABA-transaminase inhibitor, amino oxyacetic acid (AOAA), led to a 46% increase in the number of cell somata immunoreactive for GABA. This probably results from an accumulation of GABA, reflecting GABA synthesis by glutamate decarboxylase (GAD) activity, in somata of interneurons that had initially a GABA content below the immunocytochemical detection threshold. In kindled rats, 31 days after the last seizure, the number of GABA-immunoreactive cells that could be observed after AOAA-treatment was significantly lower (35% ipsilateral and 25% contralateral) when compared to AOAA-treated controls. This suggests that in kindled animals a GAD dependent increase in GABA content did not take place in a subpopulation of interneurons. The observations for kindled rats are interpreted as a long-term decrease in GABA content and as an alteration in GABA turnover in a subpopulation of interneuron somata, the latter possibly due to a decrease in GAD activity. The long-term enhanced seizure sensitivity, characteristic for kindled animals, may be due to a decreased GABAergic inhibitory control of the neuronal circuitry in the CA1 region of the hippocampus.

Aminooxyacetic Acid↗

PubMed1989

Transient increase of cytoplasmic calcium concentration in the rat hippocampus after kindling-induced seizures. An ultrastructural study with the oxalate-pyro-antimonate technique.

Kindling stimulations were applied to the Schaffer collateral/commissural fibers in the CA1 area of the dorsal rat hippocampus. In fully kindled animals the ultrastructural distribution of calcium was studied at different time intervals after an induced generalized seizure, using the oxalate-pyro-antimonate technique. Semi-quantitative analysis of the amount of precipitate revealed no change in the investigated structures analysed after 2 h or 24 h: boutons and spines of the Schaffer-collateral/pyramidal-dendrite synaptic contacts, cytoplasm and mitochondria of terminals on pyramidal cell bodies and smooth dendrites. The major change was found 15 min after a seizure, when calcium precipitate in boutons and spines of stratum radiatum was strongly increased, precipitate in somata terminals only slightly, while smooth dendrites were not affected. These results imply a seizure-related increase of the intracellular calcium concentration. The transient character suggests that the investigated cellular compartments in kindled tissue are still capable of maintaining calcium homeostasis. The observed increase in precipitate density for at least 15 min may initiate the neurochemical mechanisms leading to an enhanced seizure sensitivity in the kindling model of epilepsy.

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