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)

Status epilepticus of greater than 30-min duration in rats gives rise to a conspicuous lesion in the substantia nigra pars reticulata (SNPR) and globus pallidus (GP). The objective of the present study was to explore whether the lesion, which encompasses necrosis of both neurons and glial cells, is related to intra- and extracellular acidosis. Using the flurothyl model previously described to produce seizures, we assessed regional pH values with the autoradiographic 5,5-dimethyl[2-14C]oxazolidine-2,4-dione technique. Regional pH values were assessed in animals with continuous seizures for 20 and 60 min, as well as in those allowed to recover for 30 and 120 min after seizure periods of 20 or 60 min. In additional animals, changes in extracellular fluid pH (pHe) were measured with ion-selective microelectrodes, and extracellular fluid (ECF) volume was calculated from the diffusion profile for electrophoretically administered tetramethylammonium. In structures such as the neocortex and the hippocampus, which show intense metabolic activation during seizures, status epilepticus of 20- and 60-min duration was accompanied by a reduction of the "composite" tissue pH (pHt) of 0.2-0.3 unit. Recovery of pHt was observed upon termination of seizures. In SNPR and in GP, the acidosis was marked to excessive after 20 and 60 min of seizures (delta pHt approximately 0.6 after 60 min).(ABSTRACT TRUNCATED AT 250 WORDS)
J Cereb Blood Flow Metab 1989 Dec
PMID:Seizure-induced damage to substantia nigra and globus pallidus is accompanied by pronounced intra- and extracellular acidosis. 258 76

A spectacular spongiotic lesion, symmetrical in distribution and restricted to the pars reticulata of the substantia nigra (SNPR) has recently been described in hyperglycemic rats surviving 1-18 h after a brief period of transient ischemia. The purpose of this study was to clarify the pathogenesis of the lesion. In order to study whether the lesion was due to changes occurring during ischemia, local cerebral blood flow (l-CBF) and energy metabolites were measured in the substantia nigra (SN) and in other brain areas. Furthermore, brains were examined by light and electron microscopy immediately after ischemia and in the early recirculation period. Autoradiographic CBF measurements showed ischemia flow levels in the SN of 30-40% of control, similar in normo- and hyperglycemic rats. Thus, although ischemic, this structure had a considerable amount of residual flow. There was also a corresponding partial preservation of the adenylate energy charge. However, lactate levels were high, and in hyperglycemic subjects they rose to values previously described during status epilepticus (about 25 mumol/g). In hyperglycemic animals, neuronal alterations were consistently present in SNPR by the end of the 10-min period of ischemia. They included clumping of nuclear chromatin and subplasmalemmal clearing of the perikaryon. Some mitochondrial swelling was present in neuronal perikarya and in dendrites. The normal alignment of microtubules in the dendrites was disturbed, but there was no or only slight swelling of the dendrites. Aggregation of synaptic vesicles was a conspicuous finding in axonal terminals, which were also slightly swollen. Otherwise, the axons appeared largely spared. Microvessels looked quite intact. Similar cellular changes were observed in the early recovery period. Dendrites, however, started to swell, and their expansion finally caused the spongiotic appearance of the pars reticulata. The appearance of the dendritic lesions is strongly suggestive of transmitter-mediated ("excitotoxic") damage. However, it seems likely that the marked acidosis is injurious as well. We tentatively conclude that both mechanisms interact to give the final lesion. The results, and those previously obtained in epileptic seizures, suggest that mitochondria of SN neurons and neuronal processes are particularly prone to damage.
J Cereb Blood Flow Metab 1988 Jun
PMID:Pathogenesis of substantia nigra lesions following hyperglycemic ischemia: changes in energy metabolites, cerebral blood flow, and morphology of pars reticulata in a rat model of ischemia. 336 99

The brain uptake of phenobarbital during prolonged status epilepticus (3 h) was studied in paralyzed, ventilated sheep. The first 30 min of status epilepticus was characterized by systemic hypertension, increased CBF, increased peripheral vascular resistance, a fall in brain pH, and an elevation in brain lactate concentrations. Subsequently, hemodynamic factors normalized and brain acidosis persisted. Phenobarbital administered during the early phase of status epilepticus produced higher levels of brain phenobarbital concentration, which was greatest at the earliest sample time (5 min following infusion), compared to nonseizure controls. This elevation persisted for the first 3 h following the infusion. Phenobarbital administration during the established phase of status epilepticus, when systemic blood pressure, peripheral vascular resistance, and CBF had returned to preseizure values, resulted in attenuated brain phenobarbital uptake not different from controls for the first 30 min. These results are explained by disruption of the blood-brain barrier to phenobarbital during the early (hypertensive) phase of status epilepticus.
J Cereb Blood Flow Metab 1987 Dec
PMID:Brain phenobarbital uptake during prolonged status epilepticus. 369 34

The substantia nigra pars reticulata (SNPR) has previously been shown to undergo tissue necrosis following status epilepticus induced by flurothyl in the rat. Even if the rat is ventilated, the SNPR develops necrosis if the epileptic period lasts more than 30 min. Rat brains were frozen in situ after 20 and 60 min of seizure activity and after 60 min of seizure activity followed by 60 min recovery. Labile energy metabolites were then analyzed in the SNPR and in the periaqueductal grey matter (PAG, control region). In the PAG, the metabolite changes during status epilepticus were similar to those reported for cerebral cortex and hippocampus. Measurements showed an unchanged ATP content and energy charge (97% and 98% of control, respectively) and an accumulation of lactate to 9.2 +/- 0.6 mumol/g in the 60-min group. In the PAG, all metabolites measured had returned to control values after 60 min of recovery. In the SNPR, the perturbation of the energy metabolites was much more pronounced during status epilepticus. The concentration of ATP decreased to 75 +/- 3%, the energy charge to 91% +/- 12% and the adenylate pool to 86.7 +/- 5.7% of control. Lactate accumulated to concentrations of 16.1 +/- 1.8 mumol/g and 24.9 +/- 2.3 mumol/g in the 20-min and 60-min groups, respectively. The concentration of lactate was still increased above control after 60 min recovery, whereas the concentration of ATP and the energy charge were lower than control. The findings demonstrate that sustained and intense neuronal activation can cause metabolic disturbance and thereby lead to necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cereb Blood Flow Metab 1987 Feb
PMID:Metabolic alterations underlying the development of hypermetabolic necrosis in the substantia nigra in status epilepticus. 380 59

Cerebral oxygenation initially increases and later decreases in rats subjected to experimental status epilepticus. In this study, we have compared cerebral oxygen supply and vascular changes during paroxysmal events of different durations and at different time intervals to test the hypothesis that oxygen insufficiency is associated more readily with paroxysmal events of greater intensity. Continuous measurements were made of local changes in cortical blood volume, redox levels of cytochrome a, a3, cortical Po2, and systemic arterial blood pressure during recurrent seizures induced by pentylenetetrazol or bicuculline. In contrast to expectations, systemic and cerebral vascular responses and associated increases in cerebral oxygenation were better maintained during long-duration ictal episodes than during short-duration ictal bursts, interictal spikes, or evoked potentials. Short-duration paroxysmal events were often accompanied by decreases in cerebral oxygenation, whereas long-duration events were still accompanied by increases in oxygenation. Ictal bursts occurring with short interburst intervals caused a more rapid failure of vascular responsiveness than those occurring at longer intervals. These relationships of intensity and frequency of repetition of seizures to changes in vascular responses indicate progressive dissociation of the normally tight couple between neuronal activity, energy demand, and cerebral blood flow during status epilepticus.
J Cereb Blood Flow Metab 1983 Sep
PMID:Importance of vascular responses in determining cortical oxygenation during recurrent paroxysmal events of varying duration and frequency of repetition. 687 42

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.
J Cereb Blood Flow Metab 1995 Mar
PMID:Effects of pentylenetetrazol-induced status epilepticus on local cerebral blood flow in the developing rat. 786 Jun 61

We investigated whether the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) affects the cerebrovascular changes occurring in seizures induced by kainic acid (KA) in awake, spontaneously breathing rats. Blood flow and tissue PO2 and PCO2 were continuously and simultaneously measured by mass spectrometry from a cannula chronically implanted into the dorsal hippocampus, L-NAME (20 mg/kg; n = 8) or saline (n = 9) was administered i.p. 30 min prior to i.p. KA (10 mg/kg) injection. L-NAME significantly decreased hippocampal blood flow and PO2 and increased mean arterial blood pressure (MABP). In L-NAME-treated rats, seizure activity occurred about 10 min sooner than in control rats, and status epilepticus was inevitably followed by a flat electroencephalogram and sudden death. In contrast, control rats survival KA-induced seizures. Hippocampal blood flow was significantly less elevated during the seizures in L-NAME-treated rats than in control rats (maximal levels, 170 and 450%, respectively, of baseline values), though MABP remained significantly higher. Hippocampal PO2 was significantly decreased at all times after KA injection in L-NAME-treated rats, whereas it remained at or above normoxic levels in control rats. The present results show that L-NAME markedly attenuates the hippocampal blood flow and tissue PO2 changes in response to enhanced metabolic activity due to limbic seizures and suggest that NO is of major importance in cerebral blood flow control during KA-induced seizures.
J Cereb Blood Flow Metab 1994 Jul
PMID:Blockade of nitric oxide synthesis inhibits hippocampal hyperemia in kainic acid-induced seizures. 801 4

N-acetylaspartate (NAA) has been proposed as a marker of neuronal density. Therefore, regional measurement of NAA by magnetic resonance spectroscopic imaging (MRSI) may provide a sensitive method for detection of selective neuronal loss, in contrast to conventional imaging techniques such as magnetic resonance imaging (MRI). To test this hypothesis, we produced selective neuronal injury by kainate-induced status epilepticus. Three days later three-dimensional 1H-MRSI was obtained and compared with conventional T2-weighted MRI and histological findings in normal and kainate-treated rats. Reduction of NAA determined by MRSI in piriform cortex, amygdala, and hippocampus correlated well with neuronal injury determined from histology. Changes of NAA, without any MRI changes in hippocampus, indicated greater sensitivity of MRSI for detection of neuronal injury. These results are consistent with the hypothesis that reduction of NAA measured by MRSI may be a sensitive marker of neuronal injury in vivo in a variety of disease states.
J Cereb Blood Flow Metab 1994 May
PMID:N-acetylaspartate as an in vivo marker of neuronal viability in kainate-induced status epilepticus: 1H magnetic resonance spectroscopic imaging. 816 79

Our previous studies on cerebral metabolic activity in genetic absence epilepsy rats from Strasbourg (GAERS) were in favor of decreased functional activity during absences and normal or increased interictal activity. To ascertain that hypothesis, in the present study we performed continuous measurements of CBF in both children with typical absence epilepsy and GAERS, using Doppler ultrasonography and laser-Doppler flowmetry, respectively. CBF fluctuations during absences were recorded in four children between 5 and 6 years of age and 16 adult GAERS. In both children and animals, CBF measured in the middle cerebral artery and cortical capillaries, respectively, significantly decreased by a median value of 20-24% under basal levels during spontaneous absences. In GAERS, CBF levels were continuously decreased during haloperidol-induced absence status epilepticus, while they were not affected by ethosuximide. Conversely, convulsive seizures induced in rats either by kainate or picrotoxin led to a 175-664% increase in CBF levels. In conclusion, the present data show that during spontaneous absences, CBF decreases under basal levels in both cortical capillaries (GAERS) and the middle cerebral artery (children). Moreover, these fluctuations occur in vessels with normal vascular reactivity, are not mediated by changes in PO2, PCO2, or arterial blood pressure, and represent rather a response to reduced metabolic demand.
J Cereb Blood Flow Metab 1996 Jan
PMID:Absence seizures induce a decrease in cerebral blood flow: human and animal data. 853 May 47

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.
J Cereb Blood Flow Metab 1999 Feb
PMID:Correlation between hypermetabolism and neuronal damage during status epilepticus induced by lithium and pilocarpine in immature and adult rats. 1002 75


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