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

Radioimmunochemistry (RIA) and immunocytochemistry (ICC) were used to measure proenkephalin and prodynorphin peptides in the brain of a genetic model of epilepsy, the seizure-sensitive (SS) Mongolian gerbil. Brain levels of both [Met5]- or [Leu5]-enkephalin (ME-LI) and dynorphin A1-8 and dynorphin A1-17 (DN-LI) like immunoreactivity were increased in the hippocampal region of the SS gerbil. However, ME-LI and DN-LI did not follow the same patterns. ME-LI was significantly increased in the SS gerbils (post-seizure) compared to SR gerbils while ME-LI in SS (preseizure) gerbils was not significantly different from SR gerbils. DN-LI was significantly increased in the hippocampal region of both SS (preseizure) and SS (postseizure) gerbils compared to SR gerbils. These results strongly imply differences in the regulation of proenkephalin and prodynorphin metabolism in the Mongolian gerbil. The differences in metabolic regulation may signal fundamentally different roles of these opioid peptides in the modulation of seizure activity in this animal.
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PMID:Increased enkephalin and dynorphin immunoreactivity in the hippocampus of seizure sensitive Mongolian gerbils. 288 Jun 44

Numerous lines of evidence indicate that the substantia nigra (SN) facilitates the propagation of seizures in kindling and in other seizure models. Intranigral injection of dynorphin-1-13 exerted a potent seizure suppressant action in kindled rats. This seizure suppressant action was dose dependent, spatially specific for the area of the SN and was not blocked by naloxone (2 mg/kg i.p.). This finding extends previous work indicating that treatments which reduce SN output exert an anticonvulsant action and further suggests that opioid peptides endogenous to the SN may regulate seizure susceptibility in the kindling model.
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PMID:Intranigral dynorphin-1-13 suppresses kindled seizures by a naloxone-insensitive mechanism. 288 15

Kainic acid (KA), an excitatory neurotoxin, was used as a tool to study the metabolism of hippocampal opioid peptides and their functional role in the expression of wet-dog shakes (WDS). A single intracerebral injection of KA (1 microgram/rat) caused recurrent motor seizures lasting 3-6 h. During the convulsive period, native Met5-enkephalin-like (ME-LI) and dynorphin A(1-8)-like (DYN-LI) immunoreactivities in hippocampus decreased by 31 and 63%, respectively. By 24 h after dosing, the hippocampal opioid peptides had returned to control levels, and by 48 h ME-LI had increased 270% and DYN-LI 150%. Immunocytochemical analysis revealed that ME-LI and Leu5-enkephalin-like (LE-LI) immunostaining in the mossy fibers of dentate granule cells and the perforant-temporoammonic pathway had decreased visibly by 6 h and had increased markedly by 48 h following KA. A visible decrease in DYN-LI in mossy fiber axons within 6 h was followed by a substantial increase at 48 h. To determine whether the increases in hippocampal ME-LI reflected changes in ME biosynthesis, levels of mRNA coding for preproenkephalin (mRNAenk) and cryptic ME-LI cleaved by enzyme digestion from preproenkephalin were measured. Following the convulsive period (6 h), mRNAenk was 400% of control, and by 24 h, cryptic ME-LI was 300% of control. Increases in native and cryptic ME-LI and in mRNAenk were also noted in entorhinal cortex, but not in hypothalamus or uninjected striatum. Our data suggest that KA-induced seizures cause an increase in ME release, followed by a compensatory increase in ME biosynthesis in the hippocampus and entorhinal cortex. Several lines of evidence from this study have suggested that hippocampal enkephalins are intimately related to KA-elicited WDS. The shaking behavior was attenuated by pretreatment with naloxone or antisera against [Met5]-enkephalin. We also observed that KA-induced WDS can be mimicked by intrahippocampal injection of enkephalin-related peptides. Furthermore, this study demonstrated that intact dentate granule cells are essential for KA- and enkephalin-induced WDS, since a colchicine injection into the ventral hippocampus, which selectively destroys granule cells, abolished this behavior.
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PMID:Kainic acid as a tool to study the regulation and function of opioid peptides in the hippocampus. 289 Feb 24

The purpose of this study was to determine the role that dentate granule cells play in wet dog shakes (WDS), behavioral seizures, and hippocampal cell loss caused by systemic administration of kainic acid (KA). Rats were given bilateral injections of colchicine (COL) into the hippocampal formation to selectively lesion dentate granule cells. Two weeks later, they were injected subcutaneously with KA and were observed for WDS and seizures. Seizures were terminated with pentobarbital 2.5 hr after KA injection, and the rats were killed 48 hr later. The integrity of hippocampal cell populations and projections to the hippocampal formation from entorhinal cortex was assessed with radioimmunoassay and immunostaining for methionine-enkephalin (ME) and dynorphin (DYN) A, as well as with Timm and Nissl staining. Results indicate that COL injections eliminated KA-induced WDS, did not affect the latency to onset of seizures, and potentiated KA-induced cell loss in the CA3 region of hippocampus. COL lesions eliminated ME and DYN immunostaining of granule cells, but not ME immunostaining of entorhinal afferents to the dentate gyrus or Ammon's horn. These findings indicate that granule cells are an essential neuronal link in the expression of KA-induced WDS, but that seizures propagate along other pathways in the limbic system.
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PMID:Dentate granule cells are essential for kainic acid-induced wet dog shakes but not for seizures. 289 98

Dynorphin A (1-13) acutely elevated the seizure threshold (ST) to the convulsant flurothyl, and this action was not blocked by naloxone. Increases in ST were also observed following i.c.v. injections of the non-opioid fragment dynorphin A (3-13). Pretreatment with dynorphin A (1-13), but not dynorphin A (3-13), non-competitively blocked the anticonvulsant effect of the mu selective opioid DAGO. Furthermore, pretreatment with dynorphin A (1-13) antagonized the delta antagonist properties of naloxone or ICI 154,129 in this seizure model. Thus, in addition to its non-opioid anticonvulsant effects, dynorphin A (1-13) exhibits unique antagonist actions which appear to be specific for the active opioid fragment.
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PMID:Dynorphin A (1-13): in vivo opioid antagonist actions and non-opioid anticonvulsant effects in the rat flurothyl test. 289 82

Light microscopic immunocytochemical techniques were used to evaluate the influence of recurrent limbic seizure activity on the immunoreactivity for 3 neuropeptides--enkephalin, dynorphin, and cholecystokinin (CCK)--contained within the mouse hippocampal mossy fiber axonal system. Seizures were induced either by the placement of a small unilateral electrolytic lesion in the dentate gyrus hilus or by intraventricular injection of kainic acid. Both treatments induce epileptiform activity in hippocampus lasting several hours. Four days after either lesion placement or injection of 0.05-0.1 microgram kainic acid, immunoreactivity for all 3 peptides was altered throughout the intact mossy fiber system, bilaterally, but in distinctly different ways: enkephalin immunoreactivity (ENK-I) was dramatically elevated, dynorphin immunoreactivity was reduced, and CCK immunoreactivity (CCK-I) was either severely reduced or completely absent in the mossy fiber system. ENK-I was also clearly increased in other areas, including the lateral septum, the entorhinal cortex, and within the entorhinal (perforant path) efferents to temporal hippocampus. In contrast, the loss of CCK seemed restricted to the mossy fiber system in that immunostaining appeared normal in scattered hippocampal perikarya, within the dentate gyrus commissural system, as well as within other limbic structures. Four days after injections of 0.2 or 0.25 microgram kainic acid, mossy fiber ENK-I was greatly elevated, dynorphin immunoreactivity was reduced, but, unlike the situation with lower kainic acid doses, CCK-I was only modestly reduced in the mossy fibers and was clearly reduced in other hippocampal systems as well. These data indicate that epileptiform physiological activity differentially affects the regulation of 3 neuroactive peptides contained within the hippocampal mossy fiber system and suggest a mechanism through which seizurelike episodes can have a lasting influence on the operation of specific hippocampal circuitries.
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PMID:Seizures induce dramatic and distinctly different changes in enkephalin, dynorphin, and CCK immunoreactivities in mouse hippocampal mossy fibers. 289 12

The evidence accumulated so far indicates that seizure activity exerts profound changes on the metabolism of opioid peptides in the hippocampus. Our data consistently show a large transient decrease in dynorphin and a modest decrease in enkephalin in the hippocampus following either a single ECS or KA injection. These initial reductions, which are indicative of increased release, may trigger the biosynthetic process of hippocampal opioids and result in an overproduction of the peptides seen in the rebound phase. However, the amount and timing of the rebound in enkephalin and dynorphin levels in response to repeated ECS, amygdaloid kindling, or KA differ drastically: a rapid and sustained increase in ME-LI follows all three treatments, in contrast to a slow recovery after a large and sustained decrease in DN-LI induced by repeated ECS and amygdaloid kindling. These results, which are unique to the hippocampus, suggest that differential mechanisms are operative in regulating the metabolism of these two opioid peptides in the hippocampus. It is likely that a well-coordinated regulation of hippocampal function can be achieved through the differential release of enkephalin and dynorphin and their subsequent interactions at different subtypes of opioid receptors following seizure activities. From a functional point of view, our data provide a neurochemical correlate of previous reports that brain opioid peptides may mediate ECS-induced behavioral alterations, such as changes in seizure threshold, postictal depression, and retrograde amnesia. The robust changes in the levels of opioid peptides in kindled rats, plus shortening of the kindling process by pretreatment with mu opioid antagonists, strongly suggest the involvement of brain opioid peptides in the development of kindling. Finally, these studies show clear evidence that enkephalin in the hippocampus is important in KA-induced WDS, a component of the opiate withdrawal syndrome in rodents (Isaacson and Lanthorn 1981). Further studies should help distinguish the regulatory mechanisms responsible for changes in opioid peptide metabolism during states of hyperexcitability in the hippocampal formation.
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PMID:Seizure-induced alterations in the metabolism of hippocampal opioid peptides suggest opioid modulation of seizure-related behaviors. 289 42

The localization of opioid peptides in the rat hippocampal formation and the epileptogenic action of beta-endorphin and certain enkephalin analogues have led to speculations that opioids may play a role in limbic seizures. These immunochemical and electroencephalographic data are compatible with single-unit electrophysiological studies showing predominant excitations of hippocampal pyramidal neurons in CA1 and CA3 fields produced by iontophoresis of endorphins or enkephalins. These excitations are naloxone sensitive and appear to arise from a disinhibitory mechanism due to inhibition of inhibitory interneurons. Thus, intracellular recordings in in vitro preparations of hippocampus usually show opioid-induced reduction of inhibitory postsynaptic potentials. However, more recent studies suggest that a major opioid-containing pathway in the hippocampus, the mossy fiber projection from the dentate gyrus to CA3 pyramidal neurons, contains more pro-dynorphin-derived peptides than pro-enkephalin. Intracerebroventricular dynorphin does not induce epileptiform activity in the rat, and single-unit and field-potential studies show mixed effects on CA3 neuronal excitability, with more inhibitory responses than are seen with the enkephalins. Selective inactivation of mu opioid receptors reveals that dynorphin, which was previously shown to express specificity for kappa receptors, can act on delta receptors in CA1. Furthermore, a specific kappa agonist, U50,488H, has inhibitory actions when applied directly to CA3 neurons. These data suggest the presence of multiple opioid receptor types in the hippocampus. These multiple receptors may point to heterogeneous functions of the different families of opioid peptides in various regions of the hippocampus, and could explain the divergent effects reported for the various opioids and naloxone to promote or prevent paroxysmal activity.
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PMID:Opioid peptides and epileptogenesis in the limbic system: cellular mechanisms. 293 97

Microinfusion of morphine sulfate (50 nmol), [d-Ala2]-Met-enkephalin (35 nmol) or dynorphin A 1-13 (1 nmol) bilaterally into the substantia nigra significantly attenuated seizures induced by maximal electroshock in rats. This action was accompanied by stereotyped behavioral hyperactivity. These anticonvulsant and behavioral effects were antagonized by systemic naloxone administration; neither effect was observed after intranigral microinjection of dynorphin A 1-17 amide (1 nmol). These results are consistent with a mu opiate receptor-mediated inhibition of substantia nigra efferent neurons, and with the proposal that bilateral inhibition of nigral efferents attenuates seizure propagation. However, intranigral morphine failed to alter the severity of i.v. bicuculline seizures, indicating that opiate-mediated inhibition in substantia nigra is distinct from that produced by gamma-aminobutyric acid.
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PMID:Infusion of opiates into substantia nigra protects against maximal electroshock seizures in rats. 298 11

Until now, we have measured dynorphin-ir and enkephalin-ir at only a few time points after a single seizure or after multiple seizures in most of the models we have employed. Except for the genetically seizure-prone gerbil, our data consistently show a transient and robust decrease in dynorphin-ir and a sustained increase in enkephalin-ir in the hippocampal formation subsequent to kainic acid-, ECS-, or amygdaloid-kindled convulsive seizures. At this point, kainic acid appears to have the most dramatic effects on hippocampal enkephalin and dynorphin levels, causing an initial decrease followed by a rebound increase beyond control levels, which, for met5-enkephalin, is maintained for at least 2 weeks. Recurrent seizures leading to neurotoxic effects on CA3 pyramidal cells, which are not present after ECS or kindling, may underlie the sustained alteration in enkephalin metabolism after kainic acid. Further investigation into the time course of seizure-induced enkephalin and dynorphin metabolic changes using RIA, ICC, and measurements of opioid mRNA levels may reveal a common pattern of depletion due to immediate release, rebound synthesis according to the severity of demand, and stabilization at a new equilibrium over several days or even weeks in each seizure model. Our preliminary time points suggest striking differences in the rate of metabolism of hippocampal dynorphin and enkephalin in response to seizures. We would like to find out if other perturbations of the hippocampus, primarily the elimination of the influence of its known neurochemical afferents by lesion (as performed on the septohippocampal system described above) or pharmacological blockade, can alter the metabolism of hippocampal opioid peptides and influence subsequent seizure transmission. Distinguishing the physiological conditions that induce metabolic changes in discrete opioid peptidergic pathways may help us to understand how endogenous opioids are involved in the regulation of neuronal excitability in specific brain regions, as well as to understand more about the differential regulation of opioid peptide metabolism in different brain pathways.
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PMID:Modulation of opioid peptide metabolism by seizures: differentiation of opioid subclasses. 302 38


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