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)

The current treatment for soman-intoxication is the oxime HI 6 together with the anticholinergic drug atropine. This antidote combination is known to have effects on seizures, respiratory system, blood pressure and animal survival in experiments. However, the inflammatory responses following soman-intoxication leading to neuronal damage have not been fully evaluated. In this paper we focus on the cytokine IL-1beta induction in the rat brain after soman-intoxication (1.0 x LD50 and 1.1 x LD50) and during antidote treatment. We analyzed the IL-1beta levels in rat brain to determine the effects of time of antidote HI 6 and atropine; the effects of different combinations of HI 6 and atropine; and also the effects of antidotes diazepam and atropine following soman-intoxication. We observed that the initiation of the antidote combination of HI 6 and atropine following soman-intoxication was crucial for successful treatment. The study also demonstrated that atropine alone was more effective against IL-1beta up-regulation after soman-intoxication within the 2-h time frame, than the combination of the HI 6 and atropine, the therapy of choice in many countries. Furthermore, treatment with a combination of diazepam and atropine maintained IL-1beta levels at normal when administered at the onset of the seizures following soman exposure. Soman-intoxicated groups without seizures did not have an elevated cytokine level. This corroborates our earlier studies where soman-intoxicated animals with seizures had high levels of IL-1beta, while animals without seizures had normal values. Our results show that both time and the antidote regime are crucial to the success of treatment.
 ...
PMID:Effects of HI 6, diazepam and atropine on soman-induced IL-1 beta protein in rat brain. 1571 38

Various drugs have been associated with the development of thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Among the biologic agents, alpha-interferon therapy, used for treatment of hepatitis B and chronic myelogenous leukemia, has been associated with TTP in a few recent reports. The authors report the first case of TTP/HUS occurring in a metastatic melanoma patient receiving treatment with high-dose interleukin-2 (IL-2). A 57-year-old patient with malignant melanoma presented with seizures 3 days after completing the first week of high-dose IL-2, and the characteristic hematologic picture revealed TTP/HUS. This occurrence is unlikely to be explained by the association with malignant melanoma, which was not presenting with widespread visceral disease at the time of the occurrence, or by the use of other medications. Similar cytokine release profiles are encountered in TTP, HUS caused by Shiga toxin-1, HUS caused by E. coli O157, after IL-2 or IL-2-containing biochemotherapy, as well as in TTP caused by interferon-alpha. This cytokine profile could reflect a common cause, or just the presence of similar pathways involved.
 ...
PMID:Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome associated with high-dose interleukin-2 for the treatment of metastatic melanoma. 1572 58

Elevated cytokine response has been reported in patients with epileptic seizures. The objective of this study was to investigate the possible role of interleukin-6 (IL-6) in the pathogenesis of infantile spasms in West syndrome (WS). We measured IL-6 levels in cerebrospinal fluid (CSF) obtained from the newly diagnosed patients with WS. Twelve patients with WS (Group I) were classified as symptomatic WS (Group IA) in eight and as cryptogenic WS (Group IB) in four. The results were compared with control groups including patients with tonic-clonic seizures associated with two different kind of inflammation of central nervous system; Group IIA (infection): bacterial meningitis/encephalitis and Group IIB (trauma): post-traumatic seizures. There was no statistically significant difference between the mean values of CSF IL-6 levels in patients with WS (2.95 +/- 2.31 pg/ml) and those of subgroups of WS (Group IA: 2.26 +/- 2.01 pg/ml and Group IB: 4.33 +/- 2.52 pg/ml). Both control groups had highly increased IL-6 levels in CSF (Group IIA: 193.05 +/- 185.52 pg/ml and Group IIB: 112.74 +/- 167.44 pg/ml) than those of the patients with WS. Elevated IL-6 response in patients with tonic-clonic seizures associated with inflammation of central nervous system might be due to the seizures themselves or related to the underling etiology (infection or trauma). However, no elevated IL-6 response was found in patients with infantile spasms.
 ...
PMID:Cerebrospinal fluid interleukin-6 levels in patients with West syndrome. 1596 15

After intracerebral hemorrhage (ICH), many changes of gene transcription occur that may be important because they will contribute to understanding mechanisms of injury and recovery. Therefore, gene expression was assessed using Affymetrix microarrays in the striatum and the overlying cortex at 24 h after intracranial infusions of blood into the striatum of adult rats. Intracerebral hemorrhage regulated 369 of 8,740 transcripts as compared with saline-injected controls, with 104 regulated genes shared by the striatum and cortex. There were 108 upregulated and 126 downregulated genes in striatum, and 170 upregulated and 69 downregulated genes in the cortex. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed upregulation of IL-1-beta, Lipcortin 1 (annexin) and metallothionein 1,2, and downregulation of potassium voltage-gated channel, shaker-related subfamily, beta member 2 (Kcnab2). Of the functional groups of genes modulated by ICH, many metabolism and signal-transduction-related genes decreased in striatum but increased in adjacent cortex. In contrast, most enzyme, cytokine, chemokine, and immune response genes were upregulated in both striatum and in the cortex after ICH, likely in response to foreign proteins from the blood. A number of these genes may contribute to brain edema and cellular apoptosis caused by ICH. In addition, downregulation of growth factor pathways and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway could also contribute to perihematoma cell death/apoptosis. Intracerebral hemorrhage-related downregulation of GABA-related genes and potassium channels might contribute to perihematoma cellular excitability and increased risk of post-ICH seizures. These genomic responses to ICH potentially provide new therapeutic targets for treatment.
 ...
PMID:Brain genomics of intracerebral hemorrhage. 1603 71

Febrile seizures are the most common form of childhood seizures. The exact mechanism promoting convulsions during a common febrile illness remains unknown, but it is accepted that genetic influences are likely to account for at least some of the cases. Previous studies reported high interleukin-1beta levels in the cerebrospinal fluid of patients with febrile seizures. Recently, an association between a regulatory polymorphism in the genes encoding interleukin-1beta and interleukin-1Ra and febrile seizures was reported. In this study, we attempted to confirm these findings. We analyzed the cytokine gene polymorphisms of interleukin-1beta, interleukin-1alpha, and interleukin-1Ra of 73 children with febrile seizure and 152 healthy controls. The distribution of interleukin-1beta -511, interleukin-1alpha -889, and interleukin-1Ra genotypes and alleles did not differ significantly between cases and controls. Our data suggest that the studied gene polymorphisms of interleukin-1beta, interleukin-1alpha, and interleukin-1Ra do not have a significant role in the pathogenesis of febrile seizures.
 ...
PMID:Interleukin-1alpha, interleukin-1beta, and interleukin-1Ra polymorphisms in febrile seizures. 1615 20

The cytokine interleukin-1 (IL-1) is an established and important mediator of diverse forms of neuronal injury in experimental animals. However, its mechanisms of action remain largely unknown. We have reported previously that IL-1 markedly enhances excitotoxic injury induced in the rat by striatal administration of the excitotoxin alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), leading to widespread neuronal loss throughout the ipsilateral cortex. Here we tested the hypothesis that IL-1 causes this injury through induction and/or enhancement of seizure activity in the rat. Consistently with this hypothesis, intrastriatal injection of AMPA or AMPA with IL-1 in the rat brain increased c-Fos expression in regions similar to those in which c-Fos has been reported previously in response to seizures. A significant increase in cortical neuronal activity (number of c-Fos positive cells) was observed in response to AMPA with IL-1 compared with AMPA (8 hr after injection). Increased seizure duration [3,522 +/- 660 sec (SEM) vs. 1,415 +/- 301 sec; P < 0.001] and cell death volume (140 +/- 20 mm3 vs. 52 +/- 6 mm3; P < 0.001) were seen in response to coinfusion of AMPA with IL-1 vs. AMPA alone. In addition, the anticonvulsant diazepam (intraperitoneal) significantly reduced cell death (P < 0.001) and seizure duration (P < 0.001) induced by AMPA with IL-1, and a significant correlation was found between seizure duration and cell death volume. These findings support our hypothesis that IL-1 enhances excitotoxic injury by enhancement of seizures, which may be of relevance to IL-1 actions in other forms of neuronal injury, including cerebral ischemia.
 ...
PMID:Neurodegenerative actions of interleukin-1 in the rat brain are mediated through increases in seizure activity. 1635 39

The current study was aimed to characterize for the first time the alterations in the characteristic neuro-inflammatory markers triggered by sarin exposure in the rat's brain, and to investigate its dependency on seizure duration. Centrally mediated seizures are a common consequence of exposure to organophosphates (OP) despite conventional treatment with atropine and an oxime. In the present study midazolam, was used to control duration and intensity of seizures. The levels of the pro-inflammatory cytokine peptides IL-1beta, IL-6, TNF-alpha and prostaglandin E2 (PGE2) were monitored at various times after sarin exposure in the hippocampus and cortex of rats treated with midazolam following 5 or 30 min of seizure activity. Biochemical evaluation of brain tissues revealed a significant increase in the level of the pro-inflammatory peptides starting at 2 h and peaking at 2-24 h following sarin. Hippocampal values of IL1-beta increased from 1.2+/-0.1 pg/mg tissue (control), to 2.4+/-0.3 at 2 h (5 min seizure) and to 9.3+/-2.5 at 8h (30 min seizure). PGE2 level in the hippocampus increased up to 24 h following exposure (from 56+/-3 to 175+/-26 and 277+/-28 pg/mg tissue) following 5 and 30 min of seizure activity respectively. Thus, unlike limitation of seizures to 5 min by midazolam, delayed treatment (30 min) resulted in prolonged seizures and pronounced increase in cytokines and PGE2. In addition, a second increase in inflammatory markers was observed 30 days following sarin exposure only in rats treated following 30 min of seizure activity. Histological evaluation of the rat brain, conducted in this study, revealed lack of damage in the hippocampus and piriform cortex with minor lateral ventricles enlargement in few animals following 5 min of sarin-induced seizure activity. In contrast, marked histological damage to the brain was demonstrated following 30 min of seizure activity, consisting severe damage to the hippocampus, piriform cortex and some thalamic nuclei. In summary, a novel characterization of the prolonged central neuro-inflammatory process that accompanies sarin exposure is presented. The timing of the anticonvulsive treatment was shown to be crucial in modulation of the neuro-inflammatory response, and may implicate the consequent long-term brain damage.
 ...
PMID:Seizure duration following sarin exposure affects neuro-inflammatory markers in the rat brain. 1640 30

Insult to the central nervous system (CNS) induces many changes, including altered neurotransmitter expression, activation of astrocytes and microglia, neurogenesis and cell death. Cytokines and growth factors are candidates to be involved in astrocyte and microglial activation, and the up-regulation of glial fibrillary acidic protein (GFAP) is associated with brain damage. One of these candidates is leukemia inhibitory factor (LIF), a pro-inflammatory cytokine that is induced in astrocytes by brain damage or seizure. LIF also regulates expression of both neuropeptide Y (NPY) and galanin following peripheral nerve injury. To test the hypothesis that LIF regulates astrocyte, microglial and neuropeptide responses to a mild insult, we used a low-dose pilocarpine model to induce a brief seizure in LIF knock-out (KO) mice. Compared to wild type mice, the LIF KO mouse displays reduced astrocyte and microglial activation in the hippocampus. In addition, LIF KO mice display dramatically altered NPY, but not galanin, expression in response to injury. Thus, LIF is required for normal glial responses to brain damage, and, as in the periphery, LIF regulates NPY expression in the CNS.
 ...
PMID:Leukemia inhibitory factor is a key regulator of astrocytic, microglial and neuronal responses in a low-dose pilocarpine injury model. 1645 63

Cerebral involvement during malaria is a complication that leads to seizure, coma, and death. The effect of new neuroprotective therapies has not yet been investigated, although cerebral malaria shares some features with neurological stroke. Erythropoietin (EPO) is one of the more promising drugs in this area. We measured the effect of EPO on the survival of mice infected with Plasmodium berghei ANKA and demonstrated that inoculations of recombinant human EPO at the beginning of the clinical manifestations of cerebral malaria protect >90% of mice from death. This drug has no effect on the course of parasitemia. The effect of EPO was not related to either the inhibition of apoptosis in the brain or the regulation of the increase and decrease of nitric oxide production in the brain and blood, respectively. Tumor necrosis factor-alpha and interferon-gamma mRNA overexpression was inhibited by EPO, and treated mice had fewer brain hemorrhages. EPO has been used in patients with chronic diseases for years, and more recently it has been used to treat acute ischemic stroke. The data presented here provide the first evidence indicating that this cytokine could be useful for the symptomatic prevention of mortality during the acute stage of cerebral malaria.
 ...
PMID:Recombinant human erythropoietin prevents the death of mice during cerebral malaria. 1739 15

Dietary restriction (DR) increases the life span of many different organisms, and recent findings have demonstrated neuroprotective effects of DR in rodent and nonhuman primate models of neurodegenerative disorders. The neuroprotective mechanism of action of DR is unknown, but it may result from a mild cellular stress response involving increased production of neurotrophic factors. Because several different cytokines are known to be up-regulated in brain cells in response to stress, we determined whether DR affected cytokine expression in the rat brain. Levels of expression of interferon-gamma (IFN-gamma) and its receptor were significantly increased in the hippocampus of rats that had been maintained on an intermittent fasting DR regimen compared with rats on the ad libitum control diet. Pretreatment of embryonic rat hippocampal cell cultures with IFN-gamma protected neurons against glutamate-induced death. IFN-gamma-mediated neuroprotection was associated with an enhanced recovery of intracellular Ca(2+) concentrations following exposure to glutamate. Our data show that intermittent fasting DR stimulates IFN-gamma-mediated neuroprotective signaling in the hippocampus, suggesting a role for this cytokine in the previously reported ability of DR to protect neurons in animal models of severe epileptic seizures, stroke, and neurodegenerative disorders.
 ...
PMID:Interferon-gamma is up-regulated in the hippocampus in response to intermittent fasting and protects hippocampal neurons against excitotoxicity. 1652 Nov 27


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>