Biomedical subjects

W Kamphuis

Publications and source records attributed to W Kamphuis.

46 records · Page 3Linked to original sources

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.

Animals↗

PubMed1989

Paradoxical sleep deprivation does not affect neuronal excitability in the rat hippocampus.

Before, during and after paradoxical sleep deprivation, field potentials, evoked in the CA1 region and in the fascia dentata of the hippocampus by means of paired pulse stimulation, were measured. Paradoxical sleep deprivation was applied for 3 days, using the platform and the pendulum technique. No changes were observed on evoked field potential amplitude, population spike or paired pulse depression during and after the deprivation period. These results suggest that the neuronal excitability in the rat hippocampus, measured with the evoked potential technique, does not change as a result of paradoxical sleep deprivation.

Action Potentials↗

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.

Animals↗

PubMed1988

Changes in local evoked potentials in the rat hippocampus (CA1) during kindling epileptogenesis.

Electrophysiological changes occurring during the development of a kindled focus in the CA1 region of the rat hippocampus were studied in vivo. The most conspicuous changes of the field potentials (EPs) recorded from the stratum radiatum to stimulation of the Schaffer collaterals were the following: (1) a progressive decrease of the slope of the decaying phase of the EPs which was significantly different (P less than 0.02) from controls from sessions 8-12 onwards; (2) in the EPs recorded from the stratum pyramidale/oriens a population spike emerged from sessions 7-10 onwards; the ratio amplitude of the population spike/slope of the local EP increased progressively from session 8 onwards until a saturation level was reached; and (3) a progressive attenuation of paired-pulse depression; this decreased linearly with kindling session from session 1 up to session 11 (r = 0.97, P less than 0.01) and thereafter stabilized. These results are interpreted as due to a progressive imbalance between excitatory and inhibitory processes resulting in a decrease of inhibitory control in CA1 accompanied by a decrease in threshold of pyramidal neurons.

Action Potentials↗

PubMed1987

The development of changes in hippocampal GABA immunoreactivity in the rat kindling model of epilepsy: a light microscopic study with GABA antibodies.

Immunocytochemical techniques were used to study changes of GABA immunoreactivity in the rat hippocampal CA1 region during kindling epileptogenesis, gradually developing over a period of two weeks by daily electrical tetanization of Schaffer collaterals/commissural fibres. The number of GABA-immunoreactive somata per mm2 was quantified in CA1 region after 6 and 14 stimulus-induced afterdischarges and in fully kindled animals. The absolute values were compared with those obtained from controls and the relative difference between the side where the stimulations were applied and the contralateral side was determined. In comparison to controls the rats showed, after 6 afterdischarges at the ipsilateral, stimulated side, a slight increase in cell density of about 10%; after 14 afterdischarges, there was a significant increase of 38% together with an enhanced labelling density, while in fully kindled rats (34 afterdischarges) there was no significant difference with controls. At the contralateral side, we observed a different pattern of, respectively, a small decrease (17%), no significant difference, and a significant increase of 22% in fully kindled animals. This result is discussed in relation to observations that fully kindled rats, investigated 24 days after the last seizure of the acquisition phase, showed rather a significant decrease by 35% of cell density at the stimulated side and a regional loss of immunoreactivity of varicosities. At this point in time, no significant changes were found at the contralateral side. The complex time-course of GABA immunoreactivity during epileptogenesis consists of a transient increase in the early phase of kindling acquisition followed by a process of gradual reduction that leads to the long-term decrease of GABA immunoreactivity and high excitability.

Action Potentials↗

PubMed1986

Decrease in number of hippocampal gamma-aminobutyric acid (GABA) immunoreactive cells in the rat kindling model of epilepsy.

Daily repeated tetanic electrical stimulation (kindling) of hippocampus or other brain structures leads to progressive increase in epileptiform activity. Since kindling may involve changes in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), the distribution of this amino acid was studied. A significant decrease in number of GABA immunoreactive positive cell bodies in stimulated CA1 region of the rat hippocampus compared to the contralateral side was found.

Animals↗

PubMed1986

Modulation of adjuvant-enhanced delayed-type hypersensitivity by the interferon inducers poly I:C and Newcastle disease virus.

The modulation by the interferon (IFN) inducers poly I:C and Newcastle disease virus (NDV) of the effector phase of adjuvant-enhanced delayed-type hypersensitivity (DH) was studied in mice. A strongly enhanced DH was induced in mice to ultraviolet (UV) light inactivated Semliki forest virus (SFV) by the use of the adjuvant dimethyldioctadecylammonium bromide. At day 6 after intracutaneous immunization, DH was elicited with SFV and measured 24 and 48 h later as increase in footpad thickness (footpad swelling test). Systemic, intravenous administration of either poly I:C, UV-inactivated NDV, or NDV-induced IFN prior to elicitation of DH with antigen resulted in a temporarily suppressed DH reaction. Both the poor swelling at 3 h and strong swelling at 24 h were suppressed, while the swelling at 48 h was enhanced. The model described provides a sensitive in vivo method to study modulating effects of drugs and microbial agents on the effector phase of DH.

Animals↗

PubMed1986

Potentiation of the cellular immune response by adjuvants: a limited role for adjuvant induced interferon.

Adjuvants differ in capacity to induce interferon (IFN). As a consequence IFN induction by adjuvants may influence their effectiveness in enhancement of delayed type hypersensitivity (DH) reactions. In this study, the lipophilic amine dimethyl dioctadecyl ammonium bromide (DDA), the synthetic double-stranded polynucleotide polyinosinic polycytidylic acid (poly I:C), liposomes and the polyols L 101 and L 121 were compared in BALB/c mice as inducers of IFN and also as adjuvants for DH to both lysozyme and inactivated Semliki Forest virus (SFV). The antigens were injected intracutaneously, alone or mixed with adjuvant. At day 6 after the immunization, DH was elicited and measured 24 h later as increase in footpad thickness. Negatively charged liposomes and polyol L 121 were unable to enhance DH to SFV and also lack the capacity to induce IFN. Polyol L 101 induced low levels of IFN and showed only slight adjuvanticity for DH to SFV. In contrast, DDA, a moderate IFN inducer, was shown to be a very effective adjuvant for induction of DH against both lysozyme and SFV. The excellent IFN inducer, poly I:C, at the tested dose range (0.03-3.0 mg/kg), displayed only a relatively weak adjuvant activity. But low doses of poly I:C (0.03 and 0.1 mg/kg) showed still adjuvanticity in contrast to equal doses of DDA. This might be related to sufficient induction of IFN by low doses of poly I:C but not by DDA. The discrepancy observed in the relation between IFN induction and a maximal DH induction suggests that IFN is not the only factor which enhances the effectiveness of adjuvants in induction of DH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

PubMedDate not supplied

An experimental model of progressive epilepsy: the development of kindling of the hippocampus of the rat.

Kindling epileptogenesis was induced by periodic electrical stimulation of the Schaffer collateral/commissural pathway in the CA1 area of the rat hippocampus. The progressive nature of hippocampal kindling is demonstrated by a detailed description of the behavioral signs and the progressive increase of the after-discharge duration in the course of kindling acquisition. Furthermore, the evolution of the alterations in the paired-pulse local evoked field potentials and the modifications of the GABAA receptor binding and of the expression of mRNAs encoding for the subunits of the GABAA and glutamate receptors are considered. Evidence is presented that during kindling opposite changes occur in the CA1 and the fascia dentata in terms of the balance between excitation and inhibition due to contrasting changes in GABA-mediated inhibitory function.

Animals↗