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

Neuropeptides represent a new class of compounds with important implications for the understanding of the mechanisms and treatment of epileptic disorders. Several systems of peptide modulators--in particular the opioid-like peptides, vasopressin, somatostatin, thyrotropin-releasing hormone (TRH) and ACTH--have partially demonstrated endogenous roles in some forms of epilepsy. Seizures and stressful situations may release endogenous opioid peptides and mediate postictal depression and postictal seizure refractoriness. Vasopressin is believed to increase susceptibility to convulsions and may be involved in the pathogenesis of febrile convulsions. Derangements in TRH regulation may lower thresholds for seizure expression by regulating arousal systems; however, some TRH analogs have proven to be effective anticonvulsants. Long-term alterations in somatostatin regulation could be components of focal epilepsies. ACTH is particularly useful in the treatment of infantile spasms. Pharmacological effects of these and other peptides have potentials for defining new classes of anticonvulsants. Cholecystokinin (CCK) and its analogs, the opioid peptides beta-endorphin and FK33824, TRH analogs, and several dipeptides exhibit potent anticonvulsant properties in chemical, electroshock, and genetic model screens. Convulsant actions of CRF, somatostatin, TRH, vasopressin, and high doses of endorphin or enkephalins may provide new tools to study regulatory mechanisms of cerebral excitability. The enkephalin epileptogenic effect is being developed as a predictive tool for new anti-petit mal anticonvulsants. Advances in molecular biology have identified the genes of particular peptide families. A concept has developed that the large propeptide precursors, coded by these genes, whose processing leads to functional peptide formation and release, regulate peptidergic humoral responses to external stimuli. This idea may have particular application in the understanding of the genetic basis of some seizure states. Techniques for amplification of mRNA expression have identified specific neuronal proteins and peptides. Knowledge of protein and propeptide structural cleavage sites has suggested previously unknown candidates for modular systems in epileptic states. Technological advances in automated peptide sequencing and synthesis have allowed the development of metabolically resistant analogs and antagonist peptides. The anticonvulsant potencies of CCK, TRH, and opioid peptides have been defined more clearly with these methods.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuropeptides: anticonvulsant and convulsant mechanisms in epileptic model systems and in humans. 287 23

A tabular synopsis is presented for articles concerned with the effects of peptides on the central nervous system that appeared in the journal Peptides from 1980-1985. A table arranged alphabetically by peptide and one arranged by effects, both listing routes of injection, species, direction of change, and qualifying notes, provides easy cross-referencing of peptides and their effects. Over 80 peptides and over 135 effects are listed. The list of peptides includes, but is not limited to: ACTH, angiotensin, bombesin, bradykinin, calcitonin, casomorphin, CCK, ceruletide, CGRP, CRF, dermorphin, DSIP, dynorphin, endorphins, enkephalins, GRF, gastrin, LHRH, litorin, metkephamid, MIF-l, motilin, MSH, NPY, NT, oxytocin, ranatensin, sauvagine, substances P and K, somatostatin, TRH, VIP, vasopressin, and vasotocin. The list of effects includes, but is not limited to: aggression, alcohol, analgesia, attention, avoidance, behavior, cardiovascular regulation, catalepsy, conditioned behavior, convulsions, dopamine binding and metabolism, discrimination, drinking, EEG, exploration, feeding, fever, gastric secretion, GI motility, grooming, learning, locomotor behavior, mating, memory, neuronal activity, open field, operant behavior, rearing, respiration, satiety, scratching, seizure, sleep, stereotypy, temperature, thermoregulation and tolerance.
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PMID:Central nervous system effects of peptides, 1980-1985: a cross-listing of peptides and their central actions from the first six years of the journal Peptides. 353 8

Wistar rats were kindled electrically in the anterior or posterior medial amygdala of the right hemisphere. One week after the fourth stage 5 seizure, anxiety was assessed in the elevated plus maze test. Anxiety levels of rats kindled in posterior medial amygdala were reduced relative to implanted controls, but not relative to unoperated controls. Kindling of the anterior medial amygdala increased anxiety relative to implanted and unoperated controls. The different effects of kindling on behavior were unrelated to any parameter of kindling. The stress of an ICV injection of saline increased anxiety in unkindled controls but reduced anxiety in anterior medial amygdala-kindled rats. Injection stress effects on behavior were blocked by 50 micrograms of alpha-helical CRF (the CRF receptor blocker). These findings suggest that CRF released by the stress of the injection procedure mediates the behavioral effects in both kindled and control rats. In contrast, injection of CRF (2 micrograms, ICV) has no greater effect than ICV saline in anterior medial amygdala kindled rats, whereas it was anxiogenic in unkindled rats. ICV vehicle and CRF reduce kindling-induced anxiety equally. These findings suggest that CRF released during the injection procedure saturates available CRF receptors. Finally, kindling did not alter basal plasma corticosterone levels. These and other findings suggest that the anxiety-modulating actions of CRF are at central CRF receptors.
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PMID:Amygdala kindling, anxiety, and corticotrophin releasing factor (CRF). 841 32

Cocaine stimulates the secretion of corticosterone and ACTH, probably through a CRF-related mechanism, indicating that the drug activates the HPA axis. Indeed, cocaine has been reported to produce anxiety and to precipitate episodes of panic attack during chronic use and withdrawal in humans and to induce anxiogenic behavior in animals. Cocaine also alters benzodiazepine receptor binding in discrete regions of the rat brain. Some of these changes in binding are obviously related to the convulsions and seizures which are often observed in an acute cocaine overdose. However, data from behavioral studies have suggested that some of these effects may be related directly to cocaine reinforcement since receptor changes also were observed when binding in the brains of rats that self-administered cocaine was compared with that from animals that had received identical yoked, but non-contingent infusions of the drug. In this regard, pretreatment with the benzodiazepine receptor agonists chlordiazepoxide and alprazolam decreased cocaine self-administration without decreasing food-reinforced responding, suggesting that these effects were specific for cocaine. Since this attenuation of self-administration was reversed by increasing the unit dose of cocaine, it is likely that these drugs were decreasing cocaine reinforcement. In contrast, exposure to stress increases vulnerability to self-administer psychostimulants. In these experiments, low-dose cocaine self-administration was related directly to stress-induced increases in plasma corticosterone, such that plasma corticosterone was always greater than 150 ng/ml for rats which subsequently self-administered cocaine at doses of 0.125 mg/kg/infusion or lower, suggesting a threshold for the hormone in cocaine reinforcement. In other experiments, bilateral adrenalectomy completely abolished the acquisition of intravenous cocaine self-administration in naive rats, while metyrapone decreased ongoing self-administration. In addition, ketoconazole pretreatment resulted in patterns of self-administration that were virtually indistinguishable from that observed during saline extinction, suggesting that plasma corticosterone is not only important, but may even be necessary for cocaine reinforcement. The mechanisms through which adrenocorticosteroids alter cocaine reinforcement remain to be determined, but there is increasing evidence that the mesocorticolimbic dopaminergic system is involved. In particular, the medial prefrontal cortex appears to be at least one brain region where dopamine and adrenocorticosteroids may interact to affect cocaine reinforcement.
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PMID:A neuroendocrine role in cocaine reinforcement. 922 28

Chronic limbic epilepsy was induced in male albino rats by a single systemic injection of lithium (3 mEq/kg) and pilocarpine (30 mg/kg). During the subsequent months the numbers of spontaneous, paroxysmal stereotyped episodes (analogous to Racine stages 4 and 5) were monitored. The numbers of these "overt seizures" increased within 10 min of the daily presentation of a food stimulus even though food was available ad libitum. The majority of the paroxysmal, stereotyped behaviours occurred within 1 min of the stimulus presentation; they were attenuated by oral prednisolone. Three rats displayed evidence of "conditioned seizures" to specific stimuli. The results suggest that the display of these behaviours can be synchronized and learned in contexts that are associated with the release of CRF (corticotrophin releasing factor) and may involve the disinhibited activity within the central amygdaloid nucleus of these rats. Implications for the occurrence of psychogenic seizures in patients with complex partial (limbic) epilepsy are discussed.
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PMID:Synchronized feeding as a "conditioned stimulus" for overt seizures in chronically (limbic) epileptic rats: a model for "psychogenic seizures" with complex partial epilepsy. 1126 18

Forty five (24 male & 21 female) moderate to severe degree of predialysis CRF patients were prospectively studied over a period of 6 months (July- December, 2004) to see the effect of Recombinant Human Erythropoietin (rHuEpo/EPO) therapy on renal anaemia, progression of renal excretory function & quality of life at 3 and 6 months intervals from the starting of EPO therapy. Mean +/- SD age of the patients was 56 +/- 12 (30-77 yrs) and causes of CRF were Diabetic Nephropathy (DN)=15 (33%), Chronic Glomerulonephritis (CGN) =14(31%), Hypertension (HTN)=11(21%), Chronic Pyelonephritis (CPN)=03 (6.5%) and Obstructive Uropathy (OU)=02 (4.5%). Doses of rHuEpo was 80-100 IU/k week subcutaneously (SC) until the target Hb 11gm% & Hct 30% were achieved; there after the dose was titrated as appropriate. Serum Iron & Ferritin levels were also kept within normal reference level by iron therapy during the study period. Mean +/- SD base line (before starting EPO therapy) level of haemoblobin were 8.4 +/- 0.81(gm%), Hct 27.86 +/- 1.6 (%), blood urea 21.72 +/- 10.5 (mmol/L), S. creatinine 431.93 +/- 228.79 (mmol/L) & Ccr. 21.25 +/- 10 mum respectively. The results showed that significant improvement of haemoglobin level occurred (gm%) from 8.4 +/- 0.81 (gm%) to 9.51 +/- 1.02 (p<0.001) at 3 months and 8.4 +/- 0.81 to 11.10 +/- 1.4, (p<0.001) at 6 months interval. Haematocrit (Hct%) value also significantly increased from 27.86 +/- 1.5 to 30.57 +/- 3.62, (p<0.001) at 3 months and 27.86 +/- 1.5 to 32.81 +/- 3.92 (p<0.001) at 6 months of EPO therapy. Mean blood urea and S. creatinine levels decreased from base line level during the study period but did not show any statistical significance. There was no significant side-effects like uncontrolled hypertension, seizure or hyperviscosity syndrome in any of the study population. The quality of life in terms of improvement of physical ability and sense of well being were also improved in all the study patients. In conclusion, this study showed that the effect of rHuEpo therapy is beneficial for the correction of renal anaemia, can delay the progression of renal failure and improvement of overall quality of life in predialysis CRF patients.
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PMID:Effect rHuEpo on predialysis CRF patients: study of 45 cases. 1696 14

The present studies characterize working memory capabilities in the El mouse model of epilepsy using a species-typical social recognition memory task. As the El mouse exhibits a stress hyper-reactivity phenotype, the impact of hypertonic saline consumption, a memory modulatory treatment, upon social recognition performance was also examined. The hypotheses under test were: (1) that seizure susceptible El mice would perform poorly in the short-term working memory task relative to seizure resistant ddY controls, and (2) that the behavioral and neural responses to stressor exposure would be atypical in El mice. Results revealed a short-term working memory deficit and altered reactivity to social, environmental, and physiological stressors in El mice. In Experiment 1, El mice exhibited poor sociability and decreased olfactory investigation times, both anxiogenic-like traits, compared to ddY controls. In Experiment 2, El mice exhibited poor working memory performance compared to capable performance in ddY controls. Social recognition memory in ddY mice was abolished, however, by salt-loading whereas El mice were unaffected by exposure to this physiological stressor. In Experiment 3, all salt-loaded mice exhibited enhanced brain stress neuropeptide (corticotropin releasing factor-CRF) content, and salt-loaded El mice exhibited a 70% reduction in handling-induced seizures. These findings suggest that El mice exhibit high emotionality as well as atypical reactions to stressor exposure, and that these characteristics impact social working memory performance and seizure susceptibility.
Seizure 2007 Jan
PMID:Short-term social recognition memory deficit and atypical social and physiological stressor reactivity in seizure-susceptible El mice. 1711 13

The effects of centrally administered tripeptide fragment CRF(4-6) of corticotropin-releasing factor on convulsive activity in outbred albino rats were investigated. The peptide CRF(4-6) (icv; 6, 30, 150 nmol/head) causes dose-dependent increase in total EEG power in 1-40 Hz frequency range as a reflection of tripeptide-induced various epileptiform EEG signs such as single peaks and spike trains without external convulsion. Higher doses of CRF(4-6) (icv; 150, 225, 300 nmol per animal) induce tonicoclonic seizures. Switching to convulsive activity occurs at CRF(4-6) dose of 150 nmol per animal: injection of this dose leads only to EEG paroxysmal activity under habitual conditions and induces pathological locomotor activation under stressing conditions. Thus, CRF(4-6) similarly to full-length corticotropin-releasing factor induces epileptiform activity in rats.
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PMID:[Epileptogenic activity of tripeptide corticotropin-releasing factor fragment (CRF(4-6))]. 1728 74

The El mouse strain provides a non-induced model of idiopathic, multifactorial epilepsy in which seizures are elicited in response to stressful environmental stimuli such as tail suspension handling. In the present studies, genetically seizure susceptible El and non-susceptible ddY control mice were exposed to tail suspension, foot-shock and social stressors in order to test the hypothesis that neural and physiological responses to such stimuli would be exaggerated in the El strain. The first experiment assessed neural cell density, stress neuropeptide (corticotropin releasing factor--CRF) levels, and plasma corticosterone activation in El and ddY mice in an unhandled control condition or following exposure to tail suspension or foot-shock stressors. The second experiment assessed brain electroencephalographic activity using telemetrically monitored skull surface electrodes in El and ddY mice exposed to tail suspension or social interaction stressors. Assessment of El mouse brains revealed higher cell counts in amygdala and elevated CRF peptide content in the paraventricular thalamic nucleus relative to ddY controls. El mice exhibited significantly elevated plasma corticosterone levels 60 min following exposure to tail suspension and foot-shock stressors relative to ddY controls. Finally, El mice exhibited significantly elevated brain electroencephalographic (1-4 Hz) activity in response to tail suspension, but not social interaction, relative to ddY controls. These results indicate that potentiated neural, endocrine and physiological activation arises in the El strain following exposure to a known seizure trigger stimulus, involuntary tail suspension handling. The findings support a diathesis-stress hypothesis in which genetically seizure susceptible El mice exhibit a multifaceted hyperreactivity to noxious environmental stimuli.
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PMID:Neural, endocrine and electroencephalographic hyperreactivity to human contact: a diathesis-stress model of seizure susceptibility in El mice. 1732 61

Despite adequate antidepressant monotherapy, the majority of depressed patients do not achieve remission. Even optimal and aggressive therapy leads to a substantial number of patients who show minimal and often only transient improvement. In order to address this substantial problem of treatment-resistant depression, a number of novel targets for antidepressant therapy have emerged as a consequence of major advances in the neurobiology of depression. Three major approaches to uncover novel therapeutic interventions are: first, optimizing the modulation of monoaminergic neurotransmission; second, developing medications that act upon neurotransmitter systems other than monoaminergic circuits; and third, using focal brain stimulation to directly modulate neuronal activity. We review the most recent data on novel therapeutic compounds and their antidepressant potential. These include triple monoamine reuptake inhibitors, atypical antipsychotic augmentation, and dopamine receptor agonists. Compounds affecting extra-monoamine neurotransmitter systems include CRF(1) receptor antagonists, glucocorticoid receptor antagonists, substance P receptor antagonists, NMDA receptor antagonists, nemifitide, omega-3 fatty acids, and melatonin receptor agonists. Focal brain stimulation therapies include vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS).
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PMID:Emerging targets for antidepressant therapies. 1950 41


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