Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunohistological and in situ hybridization techniques were used to study the influence of kainic acid-induced seizures and of pentylenetetrazol kindling on neurokinin B immunoreactivity and neurokinin B mRNA in the rat hippocampus. Pronounced increases in neurokinin B immunoreactivity were observed in the terminal field of mossy fibres 10-60 days after intraperitoneal injection of kainic acid. These slow but persistent increases in immunoreactivity were accompanied by markedly enhanced expression of neurokinin B mRNA in the granule cells and in hilar interneurons adjacent to the granule cell layer. These changes were preceded by transient increases in neurokinin B mRNA and immunoreactivity in CA1 pyramidal cell layer two and 10 days after kainic acid, which, however, subsided later on. Pentylenetetrazol kindling caused similar increases in neurokinin B mRNA expression in granule cells and in CA1 pyramidal cells, but not in hilar interneurons. In CA1, increased neurokinin B message was present two days after termination of the kindling procedure but not after 10 days. Sixty days after kainic acid injection, neurokinin B immunoreactivity extended to the inner-third of the molecular layer of the dentate gyrus. After pentylenetetrazol kindling, a neurokinin B-immunoreactive band was observed in the infrapyramidal region of CA3. Lesions of the dentate granule cells by local injection of colchicine in kainic acid-treated rats abolished the supragranular neurokinin B-positive staining, whereas it was almost unchanged after transection of the ventral hippocampal commissure. These observations suggest that neurokinin B immunoreactivity may be located in ipsilateral mossy fibres undergoing collateral sprouting to the inner molecular layer or to the infrapyramidal region in CA3, respectively. Preprotachykinin A mRNA, which encodes for neurokinin A and substance P, and substance P immunoreactivity were not changed in the hippocampus of epileptic rats compared with untreated animals. The observed changes in neurokinin B immunoreactivity and mRNA indicate that specific functional and morphological changes may be induced in hippocampal neurons by recurrent limbic seizures.
 ...
PMID:Limbic seizures cause pronounced changes in the expression of neurokinin B in the hippocampus of the rat. 127 53

Changes in concentrations of the tachykinins substance P, neurokinin A and neurokinin B were investigated in rat brains after kainic acid-induced seizures. Two different antisera, one detecting substance P specifically and one recognizing neurokinins A and B but not substance P, were used. Subsequently to the acute seizures (3 h after kainic acid) significant decreases (by 25-40%) in total neurokinin (A + B) and substance P immunoreactivities were observed in the frontal cortex, dorsal hippocampus and striatum. Depending on the brain area neurokinin immunoreactivity recovered 1-3 days after injection of the toxin and was significantly increased in the frontal cortex (by 40-60%) and the hippocampus (by 100-300%) after 10-60 days. Further analysis by high pressure liquid chromatography revealed that increases in both neurokinin A and neurokinin B concentrations contributed to the increases in total neurokinin immunoreactivity 30 days after kainic acid. At the same time significantly increased levels were also observed for substance P in the frontal cortex (by 30%). Furthermore, increases were also observed in the concentrations of neuropeptide K and gamma-preprotachykinin-A(72-92) in the frontal cortex and the hippocampus 30 days after the kainic acid treatment.
 ...
PMID:Differential changes in tachykinins after kainic acid-induced seizures in the rat. 169 65

Marked changes in the expression of the tachykinin peptide neurokinin B (NKB) have been recently observed in animal models of epilepsy. In this study we investigated mRNA levels encoding the receptor for NKB, the neurokinin-3 receptor (NK-3R), after limbic seizures induced by kainic acid (KA) in the rat. NK-3R mRNA levels were determined by nuclease protection assay at various time intervals after i.p. injection of KA in the rat. Increases of more than 200% were observed in NK-3R mRNA in the cerebellum after 7 and 30 days. In the hippocampus a moderate, reversible increase (of 70%, 1 day after KA) was seen. In the frontal cortex a reduction of NK-3R mRNA (2 days after KA) was found. In the amygdala, levels of the transcript were decreased (by 50% and more) at all intervals investigated. The decreases in mRNA levels in the amygdala are consistent with the severe damage observed in this brain area. The increases in NK-3R mRNA in the cerebellum point to the development of receptor supersensitivity and suggest a functional role of NKB in this animal model of epilepsy.
 ...
PMID:Kainic acid induced seizures cause a marked increase in the expression of neurokinin-3 receptor mRNA in the rat cerebellum. 789 59

Somatostatin-, neuropeptide Y-, neurokinin B- and cholecystokinin-containing neurons were investigated in the rat hippocampus in two chronic models of temporal lobe epilepsy, i.e. 30 days after rapid kindling or electrically induced status epilepticus (post-status epilepticus). After rapid kindling, somatostatin immunoreactivity was strongly increased in interneurons and in the outer and middle molecular layer of the dentate gyrus. In four of six post-status epilepticus rats (status epilepticus I rats), somatostatin immunoreactivity was slightly increased in the dorsal but decreased in the ventral dentate gyrus and molecular layer. Somatostatin immunoreactivity decreased in neurons of the dorsal hilus in the two other post-status epilepticus rats investigated, while a complete loss was found in the respective ventral extension (status epilepticus-II rats). These changes were associated with a different extent of neurodegeneration as assessed by Nissl staining. Similarly, neuropeptide Y immunoreactivity was enhanced in neurons of the hilus and in the middle and outer molecular layer of the dentate gyrus in the dorsal hippocampus of rapidly kindled and status epilepticus-I rats. Neuropeptide Y and neurokinin B immunoreactivity was enhanced in the mossy fibers of all post-status epilepticus rats, but not in the rapidly kindled rats. In status epilepticus-II rats, neuropeptide Y-and neurokinin B-positive fibers were also detected in the infrapyramidal region of the stratum oriens of CA3 and in the inner molecular layer of the dentate gyrus in the dorsal and ventral hippocampus respectively, labeling presumably sprouted mossy fibers. Increased staining of neuropeptide Y and neurokinin B was found in the alveus after rapid kindling. Cholecystokinin immunoreactivity was markedly increased in the cerebral cortex, Ammon's horn and the molecular layer of the dentate gyrus in the ventral hippocampus of rapidly kindled and post-status epilepticus rats. The lasting changes in the immunoreactive pattern of various peptides in the hippocampus may reflect functional modifications in the corresponding peptide-containing neurons. These changes may be involved in chronic epileptogenesis, which evolves in response to limbic seizures.
 ...
PMID:Somatostatin, neuropeptide Y, neurokinin B and cholecystokinin immunoreactivity in two chronic models of temporal lobe epilepsy. 859 52

Recent studies have demonstrated that neuropeptide expression in forebrain neurons is responsive to changes in physiological activity. This is particularly true in the hippocampus where the expression of various neuropeptides has been reported to change in distinct neuronal populations in response to seizure activity. The aim of this work is to review and integrated the information on the pathological changes and functional modifications in neuropeptide systems of the hippocampal formation in kindling and other models of limbic epilepsy. This will be done by presenting a study in which we investigated the changes in the expression of somatostatin, neuropeptide Y (NPY), neurokinin B (NKB) and cholecystokinin-octapeptide (CCK) in the rat hippocampal principal neurons during and after kindling of the hippocampus using immunocytochemistry and in situ hybridization analysis of mRNA. NPY-IR was transiently expressed in the granule cells/mossy fibres after the preconvulsive stage 2 and 2 days but not 1 week after three consecutive tonic-clonic seizures (stage 5). A more pronounced increase was observed in NKB-IR lasting 1 week after kindling acquisition. Only the NKB mRNA expression was enhanced in granule cells at these intervals. At stages 2 and 5, somatostatin- and NPY-IR and their mRNA levels were markedly increased in interneurons in the deep hilus and in the polymorphic cell layer and their presumed projections to the outer molecular layer of the dentate gyrus. NKB- and CCK-IR and their mRNAs were highly expressed in basket cells at both stages of kindling. Their IR was increased in the inner molecular layer of the dentate gyrus in the ventral hippocampus. Peptide-containing neurons in the hilus appeared well preserved in spite of a reduction of Nissl stained cells by 24 % in the stimulated and contralateral hippocampus at stage 5. In the hippocampus proper, somatostatin and NPY-IR were enhanced in the stratum lacunosum molecular while CCK-IR fibres and its mRNA were particularly expressed in the pyramidal cell layer. The number of Somatostatin-, NKB- and CCK-IR cells was increased in the subiculum. The intensity of these changes was similar 2 days after stages 2 or 5 of kindling. Less pronounced effects were observed 1 week after kindling completion. These results, in the frame of the literature data, suggest that lasting functional changes occur in distinct neuropeptide-containing neurons during limbic epileptogenesis. This may have profound effects on synaptic transmission and contribute to modulate hippocampal excitability.
 ...
PMID:Neuropeptides-immunoreactivity and their mRNA expression in kindling: functional implications for limbic epileptogenesis. 887 84

In situ hybridization and immunocytochemistry were applied to investigate changes in the expression of somatostatin, neuropeptide Y, neurokinin B, cholecystokinin, dynorphin, and Met-enkephalin in the rat hippocampus after administration of a single peroral dose of trimethyltin hydroxide (9 mg/kg). Two time intervals were investigated: 5 days after trimethyltin treatment, when CA3 damage becomes manifest and is associated with increased aggression, seizure susceptibility, and memory deficit, and 16 days after trimethyltin, when neuronal damage is almost maximal and seizure susceptibility is declining. Robust but transient increases of neuropeptide Y, neurokinin B, and Met-enkephalin mRNA levels were revealed in the granule cell layer of the dentate gyrus and increased neuropeptide Y and neurokinin B immunoreactivities were found in mossy fibers. In reverse, dynorphin mRNA and immunoreactivity were decreased transiently in the dentate gyrus and mossy fibers, respectively. Strong over-expression of NPY mRNA was also observed in hilar interneurons and in CA1 and CA3 pyramidal cells as well as in the cortex at 5 days postdosing. Cholecystokinin- or neurokinin B-containing basket cells were preserved, while somatostatin-bearing interneurons were damaged by trimethyltin exposure. These neurochemical changes induced by trimethyltin intoxication strikingly parallel to those observed in animal models of temporal lobe epilepsy and may reflect activation of endogenous protective mechanisms. It is also suggested that hilar interneurons respond differently to trimethyltin exposure, for which neuropeptides are valuable markers.
 ...
PMID:Trimethyltin intoxication induces marked changes in neuropeptide expression in the rat hippocampus. 966 Dec 51

Levels of several neuropeptides were measured in the frontal cortex, dorsal hippocampus, striatum, and amygdala/pyriform cortex in rats kindled for 5 weeks by daily injection of pentylenetetrazol (30 mg/kg, i.p.). Significantly increased concentrations (by 30 - 140%) were found in all examined brain areas for neuropeptide Y, somatostatin (except hippocampus) and neurokinin-like immunoreactivity 10 days after the last kindling session. Similar but less pronounced changes were also found 24 h after the last seizure. The increase in total neurokinin-like immunoreactivity was due to a marked increase in neurokinin B as revealed by HPLC analysis. Increases in peptide levels, however, were restricted to fully kindled animals. At the same time no changes in levels of substance P, vasoactive intestinal polypeptide and calcitonin gene-regulated peptide were observed. Cholecystokinin octapeptide was enhanced only in the hippocampus (by 46%). The increases in neuropeptide Y, somatostatin, and neurokinin-like immunoreactivity subsided after 3 months. A markedly decreased seizure threshold was observed 10 days and 2 months after the final kindling session. No nerve cell degeneration was observed in kindled rats 24 h or 10 days after the last pentylenetetrazol injection. Some animals (2 of 4), however, exhibited signs of blood - brain barrier damage when examined 24 h after the last kindling session which may reflect the preceding convulsions. No such changes were detected after 10 days. The increases in peptide levels may suggest increased activity of respective neurons which, at least to some degree, may be associated with gamma-aminobutyric acid. The changes in peptide levels may be more closely related to the kindling procedure itself than to the decreased seizure threshold of the animals.
 ...
PMID:Neuropeptide Levels after Pentylenetetrazol Kindling in the Rat. 1210 7

The granule cells of the Dentate Gyrus are one of the most exciting and intriguing cells in the central nervous system. Besides containing and releasing Glu, they have been shown to contain and release peptides (somatostatin, neuropeptide Y, neurokinin B, cholecystokinin, dynorphin, enkephalin), Zn(++) ion, and brain-derived neurotrophic factor (BDNF). The recent addition of GABA to this list suggests that these cells can also function as inhibitory cells. Indeed, evidence has been presented of co-localization of all markers of the GABAergic phenotype in granule cells: GABA, the enzyme for its synthesis (Glu decarboxylase) and the membrane and vesicular transporters of GABA. These markers of the GABAergic phenotype are up-regulated after epileptic seizures. When this occurs, monosynaptic GABA receptor-mediated transmission emerges in the mossy fiber synapse thus restraining excitation and mediating antiepileptic and neuroprotective actions.
 ...
PMID:Co-existence of GABA and Glu in the hippocampal granule cells: implications for epilepsy. 1678 72

Status epilepticus (SE) describes an enduring epileptic state during which seizures are unremitting and tend to be self-perpetuating. We describe the clinical phases of generalized convulsive SE, impending SE, established SE, and subtle SE. We discuss the physiological and biochemical cascades which characterize self-sustaining SE (SSSE) in animal models. At the transition from single seizures to SSSE, GABA(A) (gamma-aminobutyric acid) receptors move from the synaptic membrane to the cytoplasm, where they are functionally inactive. This reduces the number of GABA(A) receptors available for binding GABA or GABAergic drugs, and may in part explain the development of time-dependent pharmacoresistance to benzodiazepines and the tendency of seizures to become self-sustaining. At the same time, 'spare' subunits of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartic acid) receptors move from subsynaptic sites to the synaptic membrane, causing further hyperexcitability and possibly explaining the preserved sensitivity to NMDA blockers late in the course of SE. Maladaptive changes in neuropeptide expression occur on a slower time course, with depletion of the inhibitory peptides dynorphin, galanin, somatostatin and neuropeptide Y, and with an increased expression of the proconvulsant tachykinins, substance P and neurokinin B. Finally, SE-induced neuronal injury and epileptogenesis are briefly discussed.
 ...
PMID:Advances in the pathophysiology of status epilepticus. 1736 70

Status epilepticus (SE) describes an enduring epileptic state during which seizures are unremitting and tend to be self-perpetuating. We describe the clinical phases of generalized convulsive SE, impending SE, established SE, and subtle SE. We discuss the physiological and biochemical cascades which characterize self-sustaining SE (SSSE) in animal models. At the transition from single seizures to SSSE, GABAA (gamma-aminobutyric acid) receptors move from the synaptic membrane to the cytoplasm, where they are functionally inactive. This reduces the number of GABAA receptors available for binding GABA or GABAergic drugs, and may in part explain the development of time-dependent pharmacoresistance to benzodiazepines and the tendency of seizures to become self-sustaining. At the same time, 'spare' subunits of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartic acid) receptors move from subsynaptic sites to the synaptic membrane, causing further hyperexcitability and possibly explaining the preserved sensitivity to NMDA blockers late in the course of SE. Maladaptive changes in neuropeptide expression occur on a slower time course, with depletion of the inhibitory peptides dynorphin, galanin, somatostatin and neuropeptide Y, and with an increased expression of the proconvulsant tachykinins, substance P and neurokinin B. Finally, SE-induced neuronal injury and epileptogenesis are briefly discussed.
 ...
PMID:Advances in the pathophysiology of status epilepticus. 1778 31


1 2 Next >>