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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An experimental model of status epilepticus has been developed in the immature rat by administration of pentylenetetrazol (PTZ) using repetitive, timed intraperitoneal injections of subconvulsive doses. The pattern of behavioral signs has been well characterized in each age group, i.e. 10 (P10), 14 (P14), 17 (P17) and 21 postnatal days (P21). In this model, the dose of convulsant could be adjusted as a function of interindividual sensitivity and status epilepticus lated for quite a long duration to allow the measurement of local cerebral metabolic rates for glucose (LCMRglc) by means of the [14C]2-deoxyglucose method [J. Neurochem., 28 (1977) 897-916]. To estimate LCMRglc during status epilepticus, the lumped constant (LC) was re-calculated in controls and PTZ-treated rats. The control LC was 0.54 at P10 and 0.50-0.51 at the three older ages studied (P14, P17 and P21). During status epilepticus, it increased to 0.64 in P10 rats and decreased to 0.42 and 0.40, respectively, in P17 and P21 animals. At P14, LC was not affected by seizures. The measurements of brain lactate levels showed a large 4.5-10-fold increase in PTZ-treated rats as compared to controls at all ages. The results of the present study show that the immature brain responds to sustained seizure activity in a specific way according to its postnatal age. Moreover, our results underscore the necessity of re-calculation of LC to the quantification of LCMRglc in such pathological states, particularly in immature animals.
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PMID:An experimental model of generalized seizures for the measurement of local cerebral glucose utilization in the immature rat. I. Behavioral characterization and determination of lumped constant. 142 99

The quantitative autoradiographic [14C]2-deoxyglucose technique (2DG) was applied to measure the effects of pentylenetetrazol (PTZ)-induced status epilepticus (SE) on local cerebral metabolic rates for glucose (LCMRglc) in 10 (P10)-, 14 (P14)-, 17 (P17)- and 21 (P21)-day-old rats. To produce long-lasting SE (55 min), the animals received repetitive, timed intraperitoneal injections of subconvulsive doses of PTZ until SE was reached. At P10 and P14, SE induced a marked increase in LCMRglc which affected 66 of the 76 structures studied. Increases were especially high (200-400%) in limbic and motor cortices at P10 and in some brainstem areas at these 2 ages. At P17 and P21, average brain glucose utilization was similar in seizing and control rats, but in PTZ-treated rats reflected a redistribution in local metabolic rates with increases in brainstem, midbrain, hypothalamus and septum, decreases in cortex, hippocampus, some sensory areas and white matter and no change in many motor and limbic structures. In a few cerebral regions, such as hippocampus, dentate gyrus and mammillary body, LCMRglc did not increase at P10 and P14 and decreased at P17 and P21 in PTZ- vs. saline-treated rats. The results of the present study show that the immature brain responds to sustained seizure activity in a specific way according to its maturational state. Moreover, these data allow the mapping of the vulnerability of cerebral structures to seizures, according to their metabolic response to convulsions.
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PMID:An experimental model of generalized seizures for the measurement of local cerebral glucose utilization in the immature rat. II. Mapping of brain metabolism using the quantitative [14C]2-deoxyglucose technique. 142

The present study was devoted to the long-term effects of seizures induced by pentylenetetrazol in immature rats on cerebral metabolic rates in young adult animals. Seizures were induced by repetitive intraperitoneal injections of subconvulsive doses of pentylenetetrazol either in 10- (P10) or in 21- (P21) day-old rats. The long-term metabolic effects of the seizures were studied at P60 in 54 cerebral structures by means of the [14C]deoxyglucose method. At P60, metabolic activity was decreased in 10 brain regions of rats exposed to pentylenetetrazol at P10 and in 29 structures in rats exposed to seizures at P21. Among the structures whose metabolic activity was reduced at P60 by seizures occurring either at P10 or at P21 were mainly sensory, cortical and hippocampal regions plus mammillary body, i.e. all the structures metabolically characterized as most vulnerable to pentylenetetrazol-induced status epilepticus in our previous study [Pereira de Vasconcelos A. et al. (1992) Devl Brain Res. 69, 243-259]. In the animals exposed to seizures at P21, metabolic activity was also reduced at P60 in additional sensory and cortical regions, as well as in limbic, thalamic and hypothalamic nuclei, also considered as highly sensitive to short-term pentylenetetrazol-induced seizures [Pereira de Vasconcelos A. et. al. (1992)]. Rates of glucose utilization were also reduced in a few additional areas such as the monoaminergic cell groupings. In conclusion, there are some parallels between the structures metabolically most sensitive during pentylenetetrazol-induced status epilepticus in immature rats and the long-term regional metabolic decreases recorded at P60. Our data also confirm the well-known higher sensitivity to seizures during the third postnatal week in rodents.
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PMID:Long-term metabolic effects of pentylenetetrazol-induced status epilepticus in the immature rat. 767 78

The quantitative autoradiographic [14C]-iodoantipyrine technique was applied to measure the effects of a 30-min period of pentylenetetrazol (PTZ)-induced status epilepticus (SE) on local cerebral blood flow (LCBF) in rats 10 (P10), 14 (P14), 17 (P17), and 21 (P21) days after birth. The animals received repetitive, timed injections of subconvulsive doses of PTZ until SE was reached. At P10, SE induced a 32 to 184% increase in the rates of LCBF affecting all structures studied. In P14- and P17 PTZ-treated rats, LCBF values significantly increased in two-thirds of the structures belonging to all systems studied and were not changed by SE in the parietal cortex, dorsal hippocampus, and dentate gyrus. At P21, rates of LCBF were still increased in 48 of the 73 structures studied; however, LCBF values were decreased by SE in most cortical areas, the hippocampus, and the dentate gyrus. CBF and cerebral metabolic rate for glucose (CMRglc) remained coupled in both controls and PTZ-exposed rats. Our results show that changes in LCBF with seizures are age dependent. At the most immature ages, P10 and P14, both LCBF and local CMRglc (LCMRglc) values are largely increased by long-lasting seizures. At P17 and P21, the blood flow response to SE becomes more heterogeneous, with specific decreases in the hippocampus and cortex at P21. The absence of mismatch between LCBF and LCMRglc in PTZ-exposed rats at all ages may explain at least partly why the immature brain is more resistant to seizure-induced brain damage than the adult brain.
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PMID:Effects of pentylenetetrazol-induced status epilepticus on local cerebral blood flow in the developing rat. 786 Jun 61

In order to assess acute, short and long-term effects of seizures in the immature rat brain, we studied the metabolic, circulatory and histopathological changes induced by pentylenetetrazol (PTZ) given at postnatal day 10 (P10) or 21 (P21). Seizures were induced by repetitive subconvulsive injections of PTZ given as a first dose of 40 mg/kg followed 10 min later by 20 mg/kg. Thereafter, rats received every 10 min additional injections of PTZ 10 mg/kg until the onset of status epilepticus. Local cerebral metabolic rates for glucose (LCMRglc) were measured both during the seizures in P10 and P21 rats and in the young adult animal at P60 by means of the quantitative 2-deoxyglucose technique. Rates of local cerebral blood flow (LCBF) were determined during the seizures by the iodoantipyrine technique. Short-term histological changes were assessed by acid fuchsin and hematoxylin-eosin staining and by HSP72 immunohistochemistry. At P10, LCMRglcs uniformly increased (38-400%) over control values during seizures. At P21, metabolic increases (39-181%) occurred only in 20% of the structures while LCMRglcs decreased in most cortical, hippocampal and sensory areas as well as in mammillary body, discrete thalamic nuclei and white matter areas. At P10, LCBF rose (32-184%) in all brain structures whereas, at P21, LCBF decreased in cortical, hippocampal and sensory regions and increased in most other areas. At P60, in animals having seized at either age, significant long-term decreases in LCMRglcs were recorded in hippocampus, auditory and piriform cortex, medial geniculate body and mammillary body. In P60 animals exposed to PTZ at P10, LCMRglcs were also decreased in 3 other sensory areas. In P60 animals exposed to seizures at P21, LCMRglcs were additionally decreased in sensory regions, cortices, thalamic and hypothalamic regions. Neuronal cells were transiently stained with acid fuchsin, with a peak occurring at 24 h after the seizures. The stain was visible in all regions of cerebral cortex and hippocampus and in some thalamic and hypothalamic nuclei. This transient staining was not accompanied by cell degeneration as assessed by hematoxylin-eosin histology. No HSP72 expression could be detected 24 h after the seizures, neither at P10 nor at P21. The present study shows that the immature rat neurons undergo altered metabolic rates and local circulatory decreases in the acute phase, a change in the affinity of acid fuchsin as a short-term effect and long-term metabolic decreases. All these changes are located in the same regions, i.e., cerebral cortex, hippocampus, sensory regions as well as scattered thalamic and hypothalamic nuclei. Thus, short- and long-term metabolic changes induced by seizures can be used as an index of cell stress in the immature rat brain. Since all these changes occur in the absence of visible neuronal death, they might be related to changes in the final arborization and synaptic organization of the developing brain.
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PMID:The model of pentylenetetrazol-induced status epilepticus in the immature rat: short- and long-term effects. 898 91

In the present study, we measured the effects of pentylenetetrazol (PTZ)-induced status epilepticus on the blood-brain barrier (BBB) permeability in rats at postnatal age 10 (P10) or 21 days (P21). Seizures were induced by the repetitive injection of subconvulsive doses of PTZ until the onset of status epilepticus characterized as the loss of quadruped posture. The BBB permeability changes to the poorly diffusible amino acid [14C] alpha-aminoisobutyric acid (AIB) were measured by autoradiography at 10 min after the onset of status epilepticus. Seizures induced a generalized increase in BBB permeability to AIB that was significant in 22 and 26 regions out of the 34 studied at P10 and P21, respectively. Highest increases over control levels (> 250%) were recorded at both ages in interpeduncular nucleus, raphe nuclei and trigeminal nerve tractus. Quite high increases (> 150%) were recorded in cortical, inferior collicular and thalamic areas at P10 and in inferior colliculus, cerebellar cortex, hypothalamic and thalamic regions at P21. Cerebral blood volume measured with [14C]sucrose over a 2-min period was significantly increased over control levels in hypothalamus and cerebellum at P10 and in all brain regions, except hippocampus and brainstem, at P21. The widespread increase in BBB permeability is at least partly related to the blood pressure increase, 55 and 22% over control values at P10 and P21, respectively. In the P10 rat, generalized BBB leakage appears to be correlated to the widespread increase in cerebral metabolic and blood flow rates that we recorded previously in the same experimental conditions. Conversely, at P21, as previously shown in adults, there is a mismatch between the nature of the structures with increased BBB permeability and the regional distribution of cerebral blood flow and metabolism changes induced by PTZ seizures.
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PMID:Changes in transport of [14C] alpha-aminoisobutyric acid across the blood-brain barrier during pentylenetetrazol-induced status epilepticus in the immature rat. 899 84

Pentylenetetrazol (PTZ)-induced status epilepticus (SE) leads to acute and long-term metabolic decreases in specific brain regions of rats at 10 (P10) or 21 days after birth (P21). These decreases are not related to apparent neuronal damage. Therefore, to better understand the neuronal activation and stress response to PTZ in immature rats, we mapped the expression of c-Fos and of the 72 kDa heat-shock protein (HSP72) in the same model of severe SE induced by the repetitive i.p. injections of subconvulsive doses of PTZ. Rats were sacrificed either at 2 or 24 h after the onset of SE in order to reveal c-Fos immunoreactivity, and at 24 and 72 h for HSP72 expression. Hematoxylin-eosin staining was performed at 24, 72 and 144 h after SE. The expression of c-Fos at 2 h after SE was more marked at P21 than at P10 and was prominent at both ages in the hippocampal dentate gyrus, cerebral cortex and amygdala. Some immunoreactivity was also present in the hypothalamus, thalamus and a few brainstem and cerebellar regions at both ages. There was a good relation between the regions expressing c-Fos and those exhibiting acute metabolic decreases at P21. Conversely, PTZ seizures did not lead to any expression of c-Fos at 24 h after SE or of HSP72 at 24 or 72 h at any age. Cell density was not affected by PTZ-induced SE at any age and at any time. These results suggest that c-Fos is a useful marker of neuronal activation induced by severe and prolonged seizures in the immature brain. The lack of HSP72 and of late c-Fos expression likely reflect the absence of neuronal damage in this model of PTZ-induced SE in the immature rat.
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PMID:Effects of pentylenetetrazol-induced status epilepticus on c-Fos and HSP72 immunoreactivity in the immature rat brain. 940 20

Previous studies from our group have shown that pentylenetetrazol (PTZ)-induced status epilepticus (SE) leads to age-dependent acute and long-term metabolic and circulatory changes in immature rats. In order to define the neural substrates involved in PTZ seizures according to age, the purpose of the present study was to map the areas of cellular activation during seizures of increasing severity in 10-day-old (P10), 21-day-old (P21) and adult rats. Seizures were induced by repetitive injections of subconvulsive doses of PTZ. The total dose received by the animals ranged from 4 to 125 mg/kg. These doses induced a variety of seizure profiles including absence-like, clonic seizures and SE. The cellular activation was measured as the density of c-Fos immunoreactive cells in animals at 2 h after the onset of the seizures. In P10 rats receiving a behaviourally non-active dose of PTZ, c-Fos immunoreactivity appeared only in the amygdala. The dose of 40 mg/kg that induced absence-like seizures led to a weak c-Fos expression in the medial thalamus, some cortical areas and globus pallidus. Clonic seizures reinforced labelling in the previous areas and induced a spread of c-Fos immunoreactivity to other cortical areas, thalamus, hypothalamus and some brainstem nuclei. At that age, only SE led to a widespread and stronger expression of c-Fos which was, however, totally lacking in the midbrain, and remained incomplete in the brainstem and forebrain limbic system, including the hippocampus. In P21 and adult rats, the inactive dose of PTZ induced c-Fos immunoreactivity in thalamus and hypothalamus. With absence-like seizures, c-Fos labelling spread to the cerebral cortex, amygdala, septum and some brainstem regions. With clonic seizures, immunoreactivity was reinforced in all areas already activated by absence-like seizures, and appeared in the striatum, accumbens, brainstem and hippocampus, except in CA1. After SE, c-Fos was strongly expressed in all brain areas. The intensity of c-Fos labelling was higher in most regions of P21 compared to adult rats. These data are in agreement with the immaturity of cellular and synaptic connectivity in P10 rats, the known greater sensitivity of rats to various kinds of seizures during the third week of life and the nature of the neural substrates involved in PTZ seizures.
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PMID:Mapping of neuronal networks underlying generalized seizures induced by increasing doses of pentylenetetrazol in the immature and adult rat: a c-Fos immunohistochemical study. 975 96

The correlation between seizure-induced hypermetabolism and subsequent neuronal damage was studied in 10-day-old (P10), 21-day-old (P21), and adult rats subjected to lithium-pilocarpine status epilepticus (SE). Local CMRglc (LCMRglc) values were measured by the [14C]2-deoxyglucose method for a duration of 45 minutes starting at 60 minutes after the onset of SE, and neuronal damage was assessed by cresyl violet staining at 6 days after SE. In P21 and adult rats, LCMRglc values were increased by 275 to 875% in all thalamic, cortical, forebrain, and hypothalamic regions plus the substantia nigra. In addition, at P21 there were also large increases in LCMRglc in brainstem regions. In P10 rats, metabolic increases were mostly located in cortical and forebrain regions plus the substantia nigra but did not affect hypothalamic, thalamic, or brainstem areas. In adult rats, there was an anatomical correlation between hypermetabolism and neuronal damage. At P21, although hypermetabolism occurred in regions with damage, the extent of damage varied considerably with the animals and ranged from an almost negligible to a very extended degree. Finally, in P10 rats, although quite pronounced hypermetabolism occurred, there was no neuronal damage induced by the seizures. Thus, in the present model of epilepsy, the correlation between marked hypermetabolism and neuronal damage can be shown in adult rats. Conversely, immature rats can sustain major metabolic activations that lead either to a variable extent of damage, as seen at P21, or no damage, as recorded at P10.
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PMID:Correlation between hypermetabolism and neuronal damage during status epilepticus induced by lithium and pilocarpine in immature and adult rats. 1002 75

The lithium-pilocarpine (Li-Pilo) model of epilepsy reproduces most of the features of human temporal lobe epilepsy. In the present study, we explored the correlation between metabolic changes, neuronal damage, and epileptogenesis during the silent phase following status epilepticus (SE) induced by Li-Pilo in 10- (P10) and 21-day-old (P21) and adult rats. Cerebral metabolic rates for glucose (CMR(glcs)) were measured at 14 and 60 days after SE by the 2-[(14)C]deoxyglucose method and neurodegeneration was assessed by the silver staining and cresyl violet techniques. In P10 rats, there was no damage and no metabolic consequences at any time after SE. In P21 rats, metabolic decreases were recorded at 14 days after SE, mainly in damaged forebrain regions. Conversely at 60 days after SE, P21 rats exhibited metabolic increases in both forebrain-damaged and brain-stem-intact areas. Finally, in adult rats studied at 14 days after SE, CMR(glcs) decreased in damaged forebrain areas involved in the circuitry of spontaneous seizures and increased in nondamaged brain-stem areas involved in the remote control of epilepsy. The increase in CMR(glcs) in damaged forebrain areas of P21 rats at 60 days after SE may reflect the genesis of a new circuitry underlying the occurrence of spontaneous seizures. The metabolic increase recorded in nondamaged brain-stem areas of P21 and adult rats occurs in regions involved in the remote control of seizures and might underlie a process of protection against the occurrence of seizures.
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PMID:Progressive metabolic changes underlying the chronic reorganization of brain circuits during the silent phase of the lithium-pilocarpine model of epilepsy in the immature and adult Rat. 1071 95


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