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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reports of glucocorticoid effects on neurotrophin expression suggest that adrenal hormones may contribute to the pattern of changes in the expression of these factors induced by neuronal activity and seizures. To examine this possibility, the present study evaluated the influence of adrenalectomy on basal expression and seizure-induced alterations in levels of nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 messenger RNAs in hippocampus, entorhinal cortex, and superficial neocortex. For determination of hormone effects on basal expression, adult male rats were adrenalectomized and killed 10-14 days later with paired adrenal-intact controls. For studies of adrenal steroid involvement in expression following seizure, adrenalectomized and adrenal-intact rats received a seizure-producing lesion of the dentate gyrus hilus. Changes in neurotrophin messenger RNA content were assessed by quantitative in situ hybridization. Adrenalectomy alone had no significant effect on brain-derived neurotrophic factor messenger RNA content but did result in cell-specific decreases in nerve growth factor and neurotrophin-3 messenger RNAs. Nerve growth factor messenger RNA levels were reduced in hippocampal stratum granulosum, entorhinal cortex, and neocortex but not in cells of the hippocampal molecular layers or hilus. With adrenalectomy, neurotrophin-3 messenger RNA was virtually eliminated from CA2 stratum pyramidale, partially reduced in stratum granulosum, but unaffected in neurons of the hippocampal molecular layers or entorhinal cortex. These effects were partially reversed by corticosterone (2 mg/l) supplement to the drinking saline. In experimental-seizure rats, adrenalectomy did not alter the direction or basic pattern of seizure-induced changes in neurotrophin expression but did change the time courses and magnitudes of these effects. In all areas measured, brain-derived neurotrophic factor messenger RNA content was more greatly and persistently elevated by seizure in adrenalectomized as compared with adrenal-intact rats. In contrast, with adrenalectomy seizures induced smaller increases in nerve growth factor messenger RNA content. Adrenalectomy augmented the decrease in neurotrophin-3 messenger RNA induced by seizure in hippocampus but not in entorhinal cortex. These results demonstrate that adrenal hormones play a major role in the regulation of basal nerve growth factor and neurotrophin-3 messenger RNA expression by specific populations of forebrain neurons. Moreover, the adrenal steroids have opposite effects on activity-dependent changes in brain-derived neurotrophic factor and nerve growth factor messenger RNA levels but are not required for the basic pattern of changes in neurotrophin messenger RNA expression elicited by recurrent seizures.
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PMID:Cell-specific modulation of basal and seizure-induced neurotrophin expression by adrenalectomy. 747 46

We have previously reported that focally evoked limbic motor seizures rapidly increase levels of mRNA encoding nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) in specific limbic system areas of the adult rat brain. The present studies examined the effect of both minimal and maximal electroconvulsive shock, applied via corneal electrodes, on NGF and bFGF mRNA levels in several limbic (entorhinal cortex, hippocampus, olfactory bulb) and extralimbic (striatum and cerebellum) brain regions. By 5 h following limbic motor seizures induced by low-intensity (minimal) electroshock (LES) (0.2 s, 50-70 mA; three times over a 1-h period), bFGF mRNA was significantly increased in entorhinal cortex and hippocampus, but not in the other regions examined. In contrast, tonic extensor seizures evoked by maximal electroshock (MES) (0.2 s, 150 mA; three times over a 1-h period) were associated with a significant increase in bFGF mRNA in all limbic and extralimbic regions examined. In the same animals, increases in NGF mRNA were limited to entorhinal cortex and hippocampus. Adrenal steroids were not required for the seizure-induced increase in NGF or bFGF mRNAs, based on the finding that adrenalectomized rats exhibited electroshock-induced increases in both NGF and bFGF mRNAs equivalent to the increase observed in sham-operated rats. It is suggested that the increase in mRNA levels for the neurotrophic factors occurs selectively in those regions which are especially activated by the specific seizure model, and represents an adaptive response to repeated noninjurious neuronal stimulation.
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PMID:Regional and temporal pattern of expression of nerve growth factor and basic fibroblast growth factor mRNA in rat brain following electroconvulsive shock. 751 52

Kindling, an animal model of epilepsy wherein seizures are induced by subcortical electrical stimulation, results in the upregulation of neurotrophin mRNA and protein in the adult rat forebrain and causes mossy fiber sprouting in the hippocampus. Intraventricular infusion of a synthetic peptide mimic of a nerve growth factor domain that interferes with the binding of neurotrophins to their receptors resulted in significant retardation of kindling and inhibition of mossy fiber sprouting. These findings suggest a critical role for neurotrophins in both kindling and kindling-induced synaptic reorganization.
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PMID:A nerve growth factor peptide retards seizure development and inhibits neuronal sprouting in a rat model of epilepsy. 756 61

Hippocampal levels of mRNA encoding nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are rapidly induced by enhanced neuronal activity following seizures and glutamate or muscarinic receptor activation. However, the levels of neurotrophin-3 (NT-3) mRNA acutely decrease after limbic seizures suggesting that a different mode of regulation may exist for these neurotrophins. Here we show that BDNF and neutrotrophin-4 (NT-4), but not NT-3 itself, up-regulate NT-3 mRNA in cultured hippocampal neurons. In the rat hippocampus, the muscarinic receptor agonist, pilocarpine increased BDNF mRNA levels rapidly and those of NT-3 with a delay of several hours. Injection of BDNF into neonatal rats elevated NT-3 mRNA in the hippocampus which demonstrates that BDNF is able to enhance NT-3 expression in vivo. The regulation of NT-3 by BDNF and NT-4 enlargens the neurotrophic spectrum of these neurotrophins to include neuron populations responsive primarily to NT-3.
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PMID:Brain-derived neurotrophic factor and neurotrophin-4 increase neurotrophin-3 expression in the rat hippocampus. 774 1

Intrahippocampal injection of the endogenous excitotoxin quinolinic acid (QUIN) induces seizures together with local, delayed neurodegeneration in specific cell layers. In situ hybridization histochemistry was used to study the spatio-temporal pattern of expression of neurotrophins (NTFs) after this treatment. As in other excitatory paradigms, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRNA levels increased dramatically and transiently in dentate gyrus after the administration of 120 nmol of QUIN to the left hippocampus. BDNF, but not NGF, mRNA also increased in the hippocampal pyramidal cell layer, mainly in the CA1 field. Neurotrophin-3 (NT3) mRNA levels decreased in dentate gyrus, practically disappeared around 12 h after the insult and returned to basal levels four days later. A very different pattern of expression of NTFs was found locally: (a) upregulation of NGF and BDNF mRNAs expression was prevented in a spherical region of 1-2 mm diameter around the injection site, (b) a delayed increase in NT3 mRNA levels, beginning at 12 h and lasting for at least 4 days after the administration of QUIN, was found in the same region, in cell layers showing neurodegeneration. Pretreatment with the non-competitive NMDA antagonist MK-801 (2 mg/kg, 30 min before the insult), partially blocked the increase in both BDNF and NGF mRNAs, as well as the decrease in NT3, in the contralateral hippocampus. However, this treatment did not prevent the QUIN-induced local downregulation of NGF and BDNF. Treatment with the AMPA/kainate antagonist NBQX (30 mg/kg, 15 and 5 min before, and 10 min after the insult) did not influence the effect of QUIN upon NGF or BDNF mRNA levels, although it partially prevented the hippocampal contralateral decrease in NT3 mRNA. In conclusion, the present study strongly supports previous work concerning different regulation of BDNF/NGF respect to NT3 in seizure inducing paradigms. Moreover, the different and to some extent opposite regulation of NTFs in the hippocampal region contiguous to the injection site, respect to the remaining hippocampus, suggests a differential regulation of NTFs in QUIN-induced neurodegenerative and seizural processes. Finally, our pharmacological data, (i) show that the upregulation of NGF and BDNF mRNAs, indirectly induced by QUIN, is not mediated by AMPA receptors, and (ii) suggest other effects for QUIN, apart from the stimulation of NMDA receptors.
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PMID:Differential regulation of the expression of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 mRNAs in adult rat brain after intrahippocampal injection of quinolinic acid. 785 71

Expression of the proto-oncogene zif/268 was investigated by in situ hybridization in the hippocampus and cerebral cortex of nerve growth factor (NGF)-transgenic mice during pentylenetetrazol (PTZ)-induced seizures. NGF-transgenic mice displayed normal basal levels of zif/268 mRNA in cortex and hippocampal formation except for the dentate gyrus which contained significantly reduced levels. PTZ induced a similar transient increase of zif/268 mRNA in cortex and Ammon's horn of normal and NGF-transgenic mice. On the other hand, increase of zif/268 mRNA in the dentate gyrus was significantly lower in transgenic mice. Reduced PTZ-induced activation of zif268 may reflect a decreased sensitivity of NGF-transgenic animals to epilepsy by direct or indirect interaction of NGF with immediate early genes.
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PMID:Decreased pentylenetetrazol-induced expression of zif/268 in NGF-transgenic mice. 788 Oct 37

The expression of neuropeptides and neurotrophic factors is altered in the hippocampus after seizure induction in rats. Because the increase in brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) mRNAs precede changes in neuropeptide expression after seizure, it is possible that BDNF and NGF mediate subsequent alterations in peptide expression. To test this hypothesis directly, BDNF or NGF was infused into the hippocampus and cortex of adult rats. To ascertain the regional specificity of any observed effects of neurotrophin administration on neuropeptide expression, infusions into the striatum were also studied. To control for specificity, vehicle was also infused into the same sites. Peptide and mRNA alterations were assessed by Northern analysis, immunohistochemistry and radioimmunoassay. BDNF produced elevations of peptide and mRNA for neuropeptide Y and cholecystokinin in hippocampus and cortex, and somatostatin in cortex. BDNF increased mRNAs for neuropeptide Y, cholecystokinin, substance P and dynorphin in striatum. In contrast, BDNF decreased dynorphin peptide and mRNA in hippocampus. NGF's effects were limited to small mRNA increases, without corresponding changes in peptide levels, for neuropeptide Y in hippocampus and striatum, substance P in cortex and cholecystokinin in striatum. The distinct and limited effects of NGF infusion on neuropeptide expression demonstrate that BDNF's effects are not non-specific results of protein infusion into the brain. These findings indicate that BDNF may play a regionally specific role in modulating neuropeptide expression in the normal brain as well as in various pathophysiological states.
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PMID:Regulation of neuropeptides in adult rat forebrain by the neurotrophins BDNF and NGF. 798 76

Both RNase protection assay and in situ hybridization were used to investigate the effect of intraperitoneal injection of kainate on the messenger RNA levels for basic fibroblast growth factor in the rat central nervous system. Limbic motor seizures were produced by kainate injection and this event was followed by a significant elevation of basic fibroblast growth factor gene expression in rat hippocampus and striatum 6 h after the convulsant injection. The increase in hippocampus was maximal at 24 h and it was delayed with respect to nerve growth factor induction, which peaked 3 h after kainate injection. Animals that suffered prolonged seizure activity also showed a significant elevation of basic fibroblast growth factor gene expression four and 14 days after kainate, when no changes in nerve growth factor gene expression were observed. We show that, within the hippocampus, the increase of basic fibroblast growth factor messenger RNA was localized in dentate gyrus and the CA1 layer 6 and 24 h after kainate injection. Long-term effects on its gene expression were measurable only in the CA1 hippocampal subfield, where major cell damage and astrocytosis have been reported to occur following kainate-induced seizure activity [Ben-Ari Y. et al. (1981) Neuroscience 7, 1361-1391; Lothman E. W. and Collins R. C. (1981) Brain Res. 218, 299-318; Schwob J. E. et al. (1980) Neuroscience 5, 991-1014]. Indeed, the animals which displayed elevated messenger RNA levels for basic fibroblast growth factor four and 14 days after kainate injection showed a marked induction of messenger RNA expression for the astroglial marker glial fibrillary acidic protein. These results indicate that the glutamate analogue kainate produces short- and long-term increases of basic fibroblast growth factor messenger RNA expression with a specific anatomical pattern. Therefore, the gene expression for this neurotrophic factor is probably regulated by neuronal activity at early points in time, whereas the induction observed at later time points is related to adaptive mechanisms taking place following kainate-induced neuronal degeneration.
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PMID:Short- and long-term induction of basic fibroblast growth factor gene expression in rat central nervous system following kainate injection. 819 Feb 72

Synaptic reorganization occurs in the hippocampus following various forms of seizure activity and injury, and may contribute to epileptogenesis. To address the hypothesis that neurotrophic factors play an inductive role in synaptic reorganization following seizures, we directly measured neurotrophic activity in rat hippocampal extracts after kainate injection or prolonged stimulation of the perforant path. Serial dilutions of hippocampal extracts were added to cultures of chick dorsal root ganglia, which are known to require trophic support from nerve growth factor and other neurotrophins, or ciliary ganglia neurons, which require trophic support from ciliary neurotrophic factor. Neurotrophic activity was significantly increased in hippocampal extracts harvested from 12 h to 2 months after kainate treatment, with the peak effect seen at seven days. This neurotrophic activity was substantially blocked by an anti-nerve growth factor antibody. Extracts at seven days also showed a significant increase in ciliary neurotrophic factor-like activity. Sulfide/silver histochemistry, which stains dentate granule cell axon terminals, revealed that mossy fiber sprouting was evident two weeks following kainate treatment and increased progressively over the next two to six weeks. Perforant path stimulation that produced hyperexcitability in the dentate gyrus, but no sprouting, failed to induce changes in neurotrophic activity. These results suggest there are significant increases in neurotrophic factors following kainate-induced seizures, and the increases may be related to kainate-induced hippocampal injury rather than seizures per se. Furthermore, the timecourse of increased neurotrophic activity parallels that of mossy fiber reorganization, and is consistent with the hypothesis that neurotrophic factors play a role in the injury-induced synaptic reorganization seen in epilepsy.
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PMID:Prolonged increases in neurotrophic activity associated with kainate-induced hippocampal synaptic reorganization. 825 23

Administration of N-methyl-DL-aspartate (85 mg/ml) was given by infusion (0.14 ml/min) until a clonic seizure was elicited. In situ hybridization was used to assess regional levels of four immediate early gene messenger RNA levels (c-fos, c-jun, junB, and a nerve growth factor induced gene, NGFI-A). Messenger RNA levels were highest at 25 min following infusion of N-methyl-DL-aspartate. c-jun messenger RNA levels remained elevated for over 2 h; however, c-fos, junB and, NGFI-A messenger RNA levels had returned to control levels by this time. Expression was detected in the hippocampus, hypothalamus and piriform cortex. Pre-treatment (30 min prior to N-methyl-DL-aspartate) with the anticonvulsant drugs dizocilpine maleate (1 mg/kg) and HA 966 (200 micrograms, i.c.v.) resulted in significantly reduced immediate early gene messenger RNA levels in the hypothalamus and piriform cortex, and attenuated levels in the hippocampus. Pre-treatment with the anticonvulsant agent enadoline (3 mg/kg), given at an anticonvulsant dose, did not result in reduced immediate early gene messenger RNA levels. These results suggest that monitoring immediate early gene expression may lead to advances in the understanding of the mechanism of action of many pharmacological agents, such as the kappa-opioid agonist enadoline.
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PMID:Anticonvulsant agents, dizocilpine maleate, enadoline and HA 966 have different effects on N-methyl-DL-aspartate-induced immediate early gene induction in mice. 825 28


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