Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cognitive impairments frequently accompany epileptic disorders. Here, we examine two neuroprotective agents, the noncompetitive NMDA antagonist ketamine and the dopaminergic antagonist acepromazine, for their efficacy in attenuating cognitive impairments in the lithium-pilocarpine (LI-PILO) model of rat limbic epilepsy. Declarative-like cognitive behaviors were assessed in a Morris water maze task that consisted successively of spatial and nonspatial (cued platform) training. Whereas the ketamine-treated (Ket) LI-PILO rats performed equally in all respects to nonseized control rats for the spatial and nonspatial components of the water maze task, the acepromazine-treated (Ace) LI-PILO rats failed to demonstrate learning in either the hidden or cued platform variants of the task and did not demonstrate any place learning in the platform-removed probe trials. We further assessed nondeclarative (associative) cognitive behaviors with a standard contextual fear-conditioning protocol. LI-PILO rats treated with acepromazine failed to learn the Pavlovian relationship; Ket LI-PILO rats performed equivalently to nonseized controls. Cumulatively, these data suggest robust cognitive sparing for LI-PILO rats with pharmacological NMDA receptor antagonism following induction of status epilepticus (SE). This cognitive sparing occurs despite earlier findings that the mean amount of total brain damage with LI-PILO is equivalent for Ket and Ace rats.
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PMID:Normal spatial and contextual learning for ketamine-treated rats in the pilocarpine epilepsy model. 1515 40

Diffusion-weighted nuclear magnetic resonance (NMR) imaging (DWI) is sensitive to the random translational motion of water molecules due to Brownian motion. Although the mechanism is still not completely understood, the cellular swelling that accompanies cell membrane depolarization results in a reduction in the net displacement of diffusing water molecules and thus a concomitant reduction in the apparent diffusion coefficient (ADC) of tissue water. Cerebral regions of reduced ADC appear hyperintense in a DWI and this technique has been used extensively to study acute stroke. In addition to cerebral ischemia, reductions in the ADC of cerebral water have been observed following cortical spreading depression, ischemic depolarizations (IDs), transient ischemic attack (TIA), status epilepticus, and hypoglycemia. Although the mechanism responsible for initiating membrane depolarization varies in each case, the ensuing cell volume changes follow a similar pattern. Water ADC values are also affected by the presence and orientation of barriers to translational motion (such as cell membranes and myelin fibers) and thus NMR measures of anisotropic diffusion are sensitive to more chronic pathological states where the integrity of these structures is modified by disease. Both theoretical prediction and experimental evidence suggest that the ADC of tissue water is related to the volume fraction of the interstitial space via the electrical conductivity of the tissue. The implication is that acute neurological disorders that exhibit electrical conductivity changes should also exhibit ADC changes that are detectable by DWI. A qualitative correlation between electrical conductivity and the ADC of water has been demonstrated in a number of animal model studies and the results indicate that reduced ADC values are associated with reductions in the extracellular volume fraction and increased extracellular tortuosity. The close relationship between ADC changes and cell volume changes in various pathological states suggests that NMR measurements are also sensitive to chemical communication between cells through the extracellular space (i.e., extrasynaptic or volume transmission, VT).
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PMID:Nuclear magnetic resonance (NMR) measurement of the apparent diffusion coefficient (ADC) of tissue water and its relationship to cell volume changes in pathological states. 1518 24

A 52-year-old previously healthy woman was admitted to our hospital for status epilepticus in November 1999. She had not taken oral contraceptives. After treatment with intravenous diazepam and phenytoin, she did not develop seizures anymore. When she became alert, there was a mild left hemiparesis. Lumbar puncture showed an opening pressure of 145 mm H2O, and the cerebrospinal fluid was acellular. Cranial MR imaging demonstrated thrombosis of the superior sagittal sinus and fresh infarction in the right frontal lobe. Plasma fibrinogen, fibrin degradation product, and prothrombin fragment 1 + 2 levels were elevated. Proteins S and C activities and anti-thrombin III levels were within the normal range. Lupus anticoagulant and anti-cardiolipin antibody were negative. She was treated with continuous heparin infusion for ten days and with oral warfarin thereafter. Six months after the first admission, platelet count became more than 400 x 10(3)/microliter. In July 2002, she developed slowly progressive monoplegia of the left arm. Cranial MR imaging demonstrated patent superior sagittal sinus, fresh infarction in the right parietal lobe, and old small infarction in the right corona radiata. The patient was maintained on warfarin and 100 mg of aspirin thereafter. In September 2002, platelet count was 737 x 10(3)/microliter. Bone marrow examination showed increased megakaryopoiesis with normal erythroid and myeloid series and no chromosomal aberrations. Serum C-reactive protein and iron levels were in the normal range. An abdominal ultrasound demonstrated mild splenomegaly. Thus, we made a diagnosis of essential thrombocythemia (ET). ET causes thrombotic events in the course of the disease at a rate of 7% per year. Cerebral infarction is not uncommon, but occurrence of cerebral sinus thrombosis has been rarely reported. Recently, several cases have been reported in which cerebral infarction was the first manifestation of ET even with platelet counts lower than 600 x 10(3)/microliter. To our knowledge, there have been no reported cases of ET presenting with cerebral venous sinus thrombosis. Platelet count should be monitored in the patients with venous sinus thrombosis of undetermined etiology.
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PMID:[Superior sagittal sinus thrombosis as first manifestation of essential thrombocythemia]. 1519 36

Food deprivation has been recognized as having pronounced beneficial effects in adult animals, increasing longevity, reducing seizure susceptibility, and enhancing resistance to neurotoxins. It is not known whether food deprivation in developing animals is neuroprotective or harmful. To evaluate the effects of food deprivation on brain development, we evaluated visual-spatial learning and memory and neurogenesis in the dentate gyrus of the hippocampus in food-deprived (FD) and well-fed (WF) rats. To induce food deprivation, pups were removed from their dams for 12 hours per day from Postnatal Day (P) 2 to P19. FD and WF rat pups were then subjected to status epilepticus (SE) induced by lithium-pilocarpine at P20. After SE, neurogenesis was measured, while in another group of P38 rats, learning and memory were evaluated using the Morris water maze. Food deprivation was found to reduce neurogenesis when assessed after the period of food deprivation. Although SE reduced neurogenesis in the WF animals, it had little effect additional to food deprivation on neurogenesis in the FD rats. Compared with the WF group, FD rats had a mild impairment in memory in the water maze testing after SE. Our study demonstrates that food deprivation during the neonatal period in rats is associated with a decrease in neurogenesis and mild impairment of visual-spatial memory. Although SE decreased neurogenesis in the WF group, in FD animals, SE did not reduce neurogenesis more than what was seen with food deprivation alone. Our results suggest that although food deprivation during early development reduces dentate gyrus neurogenesis, the reduced neurogenesis is not a major factor in cognitive impairment after SE in FD rats.
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PMID:Effect of food deprivation during early development on cognition and neurogenesis in the rat. 1525 80

About 1 week after the induction of status epilepticus in male rats by a single systemic injection of lithium (3 mEq/kg) and pilocarpine (30 g/kg), rats were continuously administered one of three herbal treatments through the water supply for 30 days. A fourth group received colloidal minerals and diluted food grade hydrogen peroxide in tap water, while a fifth group of rats received only tap water (control). Herbal treatments were selected for their historical antiseizure activities and sedative actions on the nervous system. The numbers of spontaneous seizures per day during a 15 min observation interval were recorded for each rat during the treatment period and during an additional 30 days when only tap water was given. Rats that received a weak solution of the three herbal fluid extracts of Scutellaria lateri flora (Skullcap), Gelsemium sempervirens (Gelsemium) and Datura stramonium (Jimson Weed) displayed no seizures during treatment while all the other groups were not seizure-free. However, when this treatment was removed, the rats in this group displayed numbers of spontaneous seizures comparable to the controls. Although there is no proof that herbal remedies can control limbic or temporal lobe epilepsy, the results of this experiment strongly suggest that the appropriate combination of herbal compounds may be helpful as adjunctive interventions.
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PMID:Herbal treatment following post-seizure induction in rat by lithium pilocarpine: Scutellaria lateriflora (Skullcap), Gelsemium sempervirens (Gelsemium) and Datura stramonium (Jimson Weed) may prevent development of spontaneous seizures. 1547 9

Prolonged seizures in immature rats result in minimal behavioral consequences when the animals are studied later in life. Likewise, early-onset seizures are associated with minimal morphological changes. However, it is known that seizures early in life result in changes in the brain that make it more vulnerable to subsequent seizure-induced injury (the so-called two-hit hypothesis). Whether this heightened vulnerability occurs immediately after the first seizure is not known. In this study, immature rats were exposed to status epilepticus (SE) followed by a series of 25 flurothyl-induced seizures, SE alone, 25 flurothyl-induced seizures alone, or no seizures. Rats exposed to SE and flurothyl seizures performed significantly poorer in the water maze 2 weeks following the last seizure compared with the other groups. No histological lesions were seen in any of the four groups. This study suggests that SE renders the immature brain vulnerable to further seizure-induced injury and this enhanced vulnerability occurs very quickly after the SE.
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PMID:Cognitive impairment following status epilepticus and recurrent seizures during early development: support for the "two-hit hypothesis". 1558 35

The cholinergic pathways are intimately involved in the learning and memory process and disruption of this system produces impairments in many learning and memory models. Converging lines of evidence support the idea that there is an age-related decline in learning and memory in animals and this decline is strikingly similar to memory changes that occur when the cholinergic system is compromised. The purpose of this work was to evaluate whether a single administration of the muscarinic receptor agonist Pilocarpine (Pilo) could prevent the age-related learning impairment in rats. Three groups of animals received Pilo (300 mg/kg, i.p.), at 3 months of age, and the animals that did not show Status epilepticus were submitted to the water maze task 1 or 21 months after or once a month from the 4th to 24th month of age. The results showed that Pilo did not interfere with learning abilities 1-month after treatment nor in animals that were submitted to the test once a month. In addition, the animals treated with Pilo and submitted to the task 21 month after performed as well as control young rats in the training and in the testing sessions, while a marked learning impairment was detected in control old rats. These results indicate that a single administration of Pilo might prevent the age-related learning impairments in rats on a spatial task in the water maze.
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PMID:Pilocarpine prevents age-related spatial learning impairments in rats. 1569 92

Diffusion-weighted MRI (DWI) and perfusion MRI (PI) have been mainly applied in acute stroke, but may provide information in the peri-ictal phase in epilepsy patients. Both transient reductions of brain water diffusion, namely a low apparent diffusion coefficient (ADC), and signs of hyperperfusion have been reported in experimental and human epilepsy case studies. We studied 10 patients with complex partial status epilepticus (CPSE) with serial MRI including DWI and PI. All patients showed regional hyperintensity on DWI, and a reduction of the ADC in (i) the hippocampal formation and the pulvinar region of the thalamus (six out of 10 patients), (ii) the pulvinar and cortical regions (two out of 10), (iii) the hippocampal formation only (one out of 10), and (iv) the hippocampal formation, the pulvinar and the cortex (one out of 10). In all patients a close spatial correlation of focal hyperperfusion with areas of ADC/DWI change was present. In two patients hyperperfusion was confirmed in additional SPECT (single photon emission computed tomography) studies. All patients received follow-up MRI examinations showing partial or complete resolution of diffusion and perfusion abnormalities depending on the length of the follow-up interval. The clinical course, EEG and SPECT results all indicate that MRI detected changes related to prolonged epileptic activity. Combined PI and DWI can visualize haemodynamic and tissue changes after CPSE in the hippocampus, thalamus and affected cortical regions.
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PMID:Diffusion-weighted and perfusion MRI demonstrates parenchymal changes in complex partial status epilepticus. 1726 32

Catalase is one of the enzymes that convert hydrogen peroxide (H2O2) to H2O presenting a protective role against free radicals. In this study, catalase activity was determined in homogenates of striatum (ST) and prefrontal cortex (PFC) in order to examine the participation of oxidative stress (OS) on cocaine actions in mice brain. Male Swiss mice were injected (i.p.) with cocaine at low (10 and 30 mg/kg) and high doses (90 mg/kg), and observed for 1 h. After cocaine overdose (90 mg/kg) some animals presented only status epilepticus (SE) while others died after seizures. These animals were dissected and divided in two groups, SE and death. Catalase activity was also determined after pretreatment with the anticonvulsant drug, diazepam, alone or injected before cocaine 90 mg/kg, and after seizures induced by a high dose of bupropion, a known inhibitor of NE and DA reuptake used for comparison. Results showed a decrease in catalase activity of the PFC and ST after SE and death induced by cocaine and bupropion overdoses. Cocaine at low doses decreased the enzyme activity only in ST. Diazepam treatment alone and before cocaine overdose did not interfere with catalase activity. This reduction in catalase activity may reflect an increase in H2O2 content in PFC and ST. Previous data reports that H2O2 inhibits dopamine transporter activity, suggesting that the decrease in catalase activity may potentiate the toxic mechanism of drugs that inhibit monoamines reuptake. As far as we know, this is the first report showing an involvement of OS in the cocaine's central mechanism of action.
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PMID:Cocaine alters catalase activity in prefrontal cortex and striatum of mice. 1608 63

Centrally mediated seizures and convulsions are common consequences of exposure to organophosphates (OPs). These seizures rapidly progress to status epilepticus (SE) and contribute to profound brain injury. Effective management of these seizures is critical for minimization of brain damage. Nasal application of midazolam (1.5 mg/kg) after 5 min of sarin-induced electrographic seizure activity (EGSA) ameliorated EGSA and convulsive behavior (238 +/- 90 s). Identical treatment after 30 min was not sufficient to ameliorate ECoG paradoxical activity and convulsive behavior. Nasal midazolam (1.5 mg/kg), together with scopolamine (1 mg/kg, im) after 5 min of EGSA, exerted a powerful and rapid anticonvulsant effect (53 +/- 10 s). Delaying the same treatment to 30 min of EGSA leads to attenuation of paroxysmal ECoG activity in all cases but total cessation of paroxysmal activity was not observed in most animals tested. Cognitive tests utilizing the Morris Water Maze demonstrated that nasal midazolam alone or together with scopolamine (im), administered after 5 min of convulsions, abolished the effect of sarin on learning. Both these treatments, when given after 30 min of convulsions, only decreased the sarin-induced learning impairments. Whereas rats which were not subject to the anticonvulsant agents did not show any memory for the platform location, both treatments (at 5 min as well as at 30 min) completely abolished the memory deficits. Both treatments equally blocked the impairment of reversal learning when given at 5 min. However, when administered after 30 min, midazolam alone reversed the impairments in reversal learning, while midazolam with scopolamine did not. Rats exposed to sarin and treated with the therapeutic regimen with the exclusion of midazolam exhibited severe brain lesions that encountered the hippocampus, pyriform cortex, and thalamus. Nasal midazolam at 5 min prevented brain damage, while delaying the midazolam treatment to 30 min of EGSA resulted in brain damage. The addition of scopolamine to midazolam did not alter the above observation. In summary, nasal midazolam treatment briefly after initiation of OP-induced seizure leads to cessation of EGSA and prevented brain lesions and behavioral deficiencies in the rat model.
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PMID:Anticonvulsant treatment of sarin-induced seizures with nasal midazolam: an electrographic, behavioral, and histological study in freely moving rats. 1627 23


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