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)

Neurocysticercosis (NCC) is a common parasitic infection of the central nervous system (CNS) caused by larvae of Taenia solium. Most infected individuals remain asymptomatic while few develop symptoms i.e. seizures. Integrity or disruption of blood brain barrier plays an important role in CNS infection and inflammatory response. Therefore, we studied the induction of Th1 (TNF-alpha, IFN-gamma, IL-1beta and IL-2), Th2 (IL-4), IL-10 cytokines and adhesion molecule sICAM-1 in the lymphocytes isolated from symptomatic and asymptomatic NCC cases by stimulating them with Taenia solium cyst fluid antigens. The expression of TNF-alpha, IFN-gamma, IL-1beta and sICAM-1 was significantly higher only in symptomatic NCC cases. Our study highlights the role of adhesion molecules in the development of symptoms in NCC.
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PMID:Increased expression of ICAM-1 among symptomatic neurocysticercosis. 1894 84

Increasing body of evidence indicate that besides the central nervous system, antiepileptic drugs may also affect the immunoactivity. Experimental data showed that classical antiepileptic drugs affect peripheral immunological parameters. To this end, phenytoin and carbamazepine attenuate both humoral and cellular response, and an engagement of CD8+ cells in these effects was suggested. Other authors reported that valproate and phenobarbital diminished humoral response and lymphocyte T cytotoxicity in mice, respectively. On the other hand, withdrawal of carbamazepine and phenytoin enhanced autoimmune response in experimental encephalomyelitis in mice. Few data concern effects of new antiepileptic drugs on immune system. It was found that topiramate reversed seizures-induced decrease in lymphocyte T proliferative activity in rats. Some new antiepileptic drugs, e.g., felbamate, stiripentol, loreclezole and tiagabine suppress mitogenes-stimulated proliferative activity of mouse splenocytes in vitro. Results of clinical studies indicate that phenytoin, carbamazepine, and valproate, show immunosuppressive activity, inhibit protein synthesis in lymphocytes, decrease CD4+/CD8+ ratio, decrease IgA, and induce changes in IgG and IgM plasma levels. Cytokine synthesis is also affected by antiepileptic drugs, although in a complex manner. Carbamazepine inhibits IL-2 and IL-4 but stimulates IL-10 and TGFb production in vitro. Treatment of epileptic patients with carbamazepine increases IL-2 level, whereas phenytoin elevates IL-1 blood concentration. In vitro valproate inhibits TNFa and IL-6 production, whereas in epileptic patients this drug enhances IL-1, IL-6 and IL-5 concentration. With respect to undesired effects of antiepileptic drugs, lamotrigine, carbamazepine, phenobarbital and phenytoin may induce hypersensitivity of immune system. The suggested mechanism of the hypersensitivity involves activation of drug specific CD4+ and CD8+, increase in IL-4 and IL-5 level, receptor T polymorphism or direct interaction of drug with lymphocyte T receptors. Summing up, majority of antiepileptic drugs show immunosuppressive effects, however under certain conditions they can also stimulate immune system. Further studies on chronic administration of traditional and new antiepileptic drugs on immune system activity are warranted.
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PMID:[Effects of antiepileptic drugs on immune system]. 1920 64

We report the case of a girl with Tay-Sachs disease who had convulsions and deteriorated rapidly after an upper respiratory infection at the age of 11 months. At the age of 16 months, her seizures became intractable and magnetic resonance imaging of the brain showed high signal intensity on T2-weighted images and marked swelling in the white matter and basal nucelei of the right hemisphere. Her seizures and right hemisphere lesion improved with glycerol and dexamethasone treatment. When dexamethasone was discontinued, her symptoms worsened and lesions later appeared in the left hemisphere. Her cerebrospinal fluid showed elevated levels of the cytokines TNF-alpha and IL-5. It is considered that inflammation contributes to disease progression in Tay-Sachs disease.
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PMID:Unilaterally and rapidly progressing white matter lesion and elevated cytokines in a patient with Tay-Sachs disease. 1927

Tumor necrosis factor (TNF)-alpha is a proinflammatory cytokine acting on two distinct receptor subtypes, namely p55 and p75 receptors. TNF-alpha p55 and p75 receptor knockout mice were previously shown to display a decreased or enhanced susceptibility to seizures, respectively, suggesting intrinsic modifications in neuronal excitability. We investigated whether alterations in glutamate system function occur in these naive knockout mice with perturbed cytokine signaling that could explain their different propensity to develop seizures. Using Western blot analysis of hippocampal homogenates, we found that p55(-/-) mice have decreased levels of membrane GluR3 and NR1 glutamate receptor subunits while GluR1, GluR2, GluR6/7 and NR2A/B were unchanged as compared to wild-type mice. In p75(-/-) mice, GluR2, GluR3, GluR6/7 and NR2A/B glutamate receptor subunits were increased in the hippocampus while GluR1 and NR1 did not change. Extracellular single-cell recordings of the electrical activity of hippocampal neurons were carried out in anesthetized mice by standard electrophysiological techniques. Microiontophoretic application of glutamate increased the basal firing rate of hippocampal neurons in p75(-/-) mice versus wild-type mice, and this effect was blocked by 2-amino-5-phosphopentanoic acid and 6-nitro-7-sulfamoyl-benzo(f)quinoxaline-2,3-dione denoting the involvement of N-methyl-D-aspartic acid and AMPA receptors. In p55(-/-) mice, hippocampal neurons responses to glutamate were similar to wild-type mice. Spontaneous glutamate release measured by in vivo hippocampal microdialysis was significantly decreased only in p55(-/-) mice. No changes were observed in KCl-induced glutamate release in both receptor knockout mice strains versus wild-type mice. These findings highlight specific molecular and functional interactions between p55 and p75 receptor-mediated signaling and the glutamate system. These interactions may be relevant for controlling neuronal excitability in physiological and pathological conditions.
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PMID:Molecular and functional interactions between tumor necrosis factor-alpha receptors and the glutamatergic system in the mouse hippocampus: implications for seizure susceptibility. 1928 15

Early-life seizures result in increased susceptibility to seizures and greater neurologic injury with a second insult in adulthood. The mechanisms which link seizures in early-life to increased susceptibility to neurologic injury following a 'second hit' are not known. We examined the contribution of microglial activation and increased proinflammatory cytokine production to the subsequent increase in susceptibility to neurologic injury using a kainic acid (KA)-induced, established 'two-hit' seizure model in rats. Postnatal day (P)15 rats were administered intraperitoneal KA (early-life seizures) or saline, followed on P45 with either a 'second hit' of KA, a first exposure to KA (adult seizures), or saline. We measured the levels of proinflammatory cytokines (IL-1 beta, TNF-alpha, and S100B), the chemokine CCL2, microglial activation, seizure susceptibility and neuronal outcomes in adult rats 12 h and 10 days after the second hit on P45. The 'two-hit' group exposed to KA on both P15 and P45 had higher levels of cytokines, greater microglial activation, and increased susceptibility to seizures and neurologic injury compared to the adult seizures group. Treatment after early-life seizures with Minozac, a small molecule experimental therapeutic that targets upregulated proinflammatory cytokine production, attenuated the enhanced microglial and cytokine responses, the increased susceptibility to seizures, and the greater neuronal injury in the 'two-hit' group. These results implicate microglial activation as one mechanism by which early-life seizures contribute to increased vulnerability to neurologic insults in adulthood, and indicate the potential longer term benefits of early-life intervention with therapies that target up-regulation of proinflammatory cytokines.
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PMID:Enhanced microglial activation and proinflammatory cytokine upregulation are linked to increased susceptibility to seizures and neurologic injury in a 'two-hit' seizure model. 1950 Oct 63

Epilepsy is a common health problem. Although variety of factors influence the incidence and prevalence of seizures, cytokines are considered to play an important role in seizures. Cytokines are also known to be involved in other neurodegenerative disorders. Proinflammatory cytokines like IL-1, IL-6, TNF-alpha and growth factor vascular endothelial growth factor (VEGF) as well as anti-inflammatory cytokine IL-10 and related molecules have been described in CNS and plasma of experimental models of seizures and clinical cases of epilepsy. There are reports suggesting more predispositions to seizures during inflammatory conditions like colitis, pneumonia and rheumatoid arthritis. These inflammatory cytokines and growth factors are also known to have dual roles in affecting seizure susceptibility. It remains to be seen if cytokine modulators can be therapeutically exploited for patients with inflammatory disorder and suffering from epilepsy.
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PMID:Role of different cytokines and seizure susceptibility: a new dimension towards epilepsy research. 1977 68

Traumatic brain injury is a heterogeneous disease, encompassing a wide range of pathologies. The dopamine agonist lisuride is well established in the therapy of Parkinson's disease. Additionally to its dopaminergic effects it decreases prolactine release, reducing the amount of inflammatory mediators such as TNF-alpha or Il-6. Lisuride has strong binding affinity to serotonergic and histaminergic receptors on neuronal and glial cells leading to scavenging of highly reactive free radicals. Due to its interaction with dopaminergic D2 and D4 receptors as well as 5-HT-1A receptors, NMDA-receptor signaling and glutamate-mediated excitotoxicity can be modulated beneficially. Despite of these promising neuroprotective effects, experimental data scrutinizing the effects of lisuride after acute brain injury are sparse. We therefore investigated the effect of lisuride after controlled cortical impact injury (CCII) in rats. 70 male Sprague-Dawley rats were randomized to lisuride or to placebo treatment by an initial s.c. loading dose (0.3mg/kg BW) and following continuous application (0.5mg/kg/d) by s.c. implanted osmotic pumps. In three experimental groups we determined (sub)acute neuro-physiological changes after trauma. Mean arterial blood pressure, intracranial pressure, and electrical brain activity were monitored acutely for up to 3h after trauma. Brain edema formation was assessed 24h after CCII. Furthermore, contusion volumes were quantified by magnetic resonance tomography and neurological testing was performed for up to 7 days after injury. Associated with the administration of lisuride there was a significant reduction in duration and number of post-traumatic seizures. Despite of a sustained arterial hypotension following the initial bolus administration in the treatment group, contusion volumes and neurological function tests did not differ significantly in comparison to the control group. Overall, lisuride seems to have significant anticonvulsive effects but seems not to influence secondary brain damage in this experimental model.
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PMID:Anticonvulsive effects of the dopamine agonist lisuride maleate after experimental traumatic brain injury. 2005 33

Cysticercosis is an infection with larval cysts of the cestode Taenia solium. Through pathways that are incompletely understood, dying parasites initiate a granulomatous reaction that, in the brain, causes seizures. Substance P (SP), a neuropeptide involved in pain-transmission, contributes to inflammation and previously was detected in granulomas associated with dead T. crassiceps cysts. To determine if SP contributes to granuloma formation, we measured granuloma-size and levels of IL-1beta, TNF-alpha, and IL-6 within granulomas in T. crassiceps-infected wild type (WT) mice and mice deficient in SP-precursor (SPP) or the SP-receptor (neurokinin 1, NK1). Granuloma volumes of infected SPP- and NK1-knockout mice were reduced by 31 and 36%, respectively, compared to WT mice (P < .05 for both) and produced up to 5-fold less IL-1beta, TNF-alpha, and IL-6 protein. Thus, SP signaling contributes to granuloma development and proinflammatory cytokine production in T. crassiceps infection and suggests a potential role for this mediator in human cystercercosis.
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PMID:Substance P signaling contributes to granuloma formation in Taenia crassiceps infection, a murine model of cysticercosis. 2015 Sep 70

Japanese encephalitis (JE) is the commonest encephalitis in South East Asia associated with high morbidity and mortality. Neuronal injury is attributed to a number of proinflammatory cytokines. This study evaluates cerebrospinal fluid (CSF) cytokines and chemokines in encephalitis and correlates these with clinical and magnetic resonance imaging (MRI) findings. We examined 14 patients with encephalitis (8 JE, 1 dengue, 5 nonspecific encephalitis) and 10 healthy controls. CSF cytokines (IL-1beta, IL-6, IL-10, IL-12p70, TNF-alpha, IL-8) and chemokines (IP-10, MCP-1, MIG, IL-8 and RANTES) were estimated using Cytometric Bead Array, compared with controls and were correlated with severity of encephalitis, radiological findings and presence of movement disorders. Median age of the patients was 25.5 (range 6-55 years); 6 had seizures, 10 movement disorders and 6 out of 11 had MRI abnormalities. The MRI abnormalities included thalamic involvement in 5, basal ganglia and mid brain in 3 each and cortical involvement in 2 patients. Both the patients with cortical involvement had seizures and 5 of the 10 patients with movement disorders had thalamic, basal ganglia and/or mid brain involvement. There was significant increase in IL-6 (p=0.01), RANTES (p=0.02) and IL-8 (p=0.02) in encephalitis compared to controls but there was no difference in IL12p70, TNF-alpha, IL-10, IL-1beta and MCP-1. Cytokines and chemokines did not correlate with severity of encephalitis, radiological changes and presence of movement disorders. CSF IL-6, IL-8 and RANTES were significantly higher in encephalitis patients compared to controls.
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PMID:Cytokines and chemokines in viral encephalitis: a clinicoradiological correlation. 2015 11

Inflammation and genetics may play a role in the pathogenesis of febrile seizures (FSs). We aimed to test whether interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1 Ra), IL-6 promoter, IL-8, IL-10, or tumor necrosis factor (TNF) gene polymorphisms could be used as markers of susceptibility to FSs. An association study was performed among a cohort of 104 patients with FSs and 143 normal control subjects. There was no significant difference between patients and controls in the distribution of allele frequencies of the IL-1beta promoter, IL-1beta exon 5, IL-6 promoter, IL-8, IL-10, or TNF-alpha gene polymorphisms. In contrast, the IL-1 Ra-I homozygote was more frequent in patients with FSs than in healthy controls (93.2% vs. 83.92%, chi(2)=4.51, P=0.034). In addition, individuals homozygous for the IL-1 Ra-I genotype were more than twice as likely to develop FSs than individuals heterozygous for the IL-1 Ra-I/II genotype (OR, 2.63, 95% CI: 1.08-6.39; chi(2)=4.55, P=0.033). We conclude that the IL-1 Ra gene might be one of the useful markers for predicting susceptibility to FSs.
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PMID:Interleukin (IL)-1beta, IL-1 receptor antagonist, IL-6, IL-8, IL-10, and tumor necrosis factor alpha gene polymorphisms in patients with febrile seizures. 2048 95


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