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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebral superoxide anion generation during bicuculline-induced seizures was measured in newborn pigs. Using two closed cranial windows inserted over the parietal cortices, superoxide dismutase (SOD)-inhibitable nitroblue tetrazolium (NBT) reduction was determined during 20 min of seizure activity induced by bicuculline, 5 mg/kg i.v. A modest increase in SOD-inhibitable NBT reduction was observed in piglets subjected to bicuculline-induced seizure activity (2.4 +/- 0.6 pmol/mm2 in 20 min) when compared to control piglets (0.4 +/- 0.3 pmol/mm2 in 20 min). Pretreatment with indomethacin (5 mg/kg i.v.) reduced SOD-inhibitable NBT reduction during seizures to the control level (0.5 +/- 0.4 pmol/mm2 in 20 min). We conclude that small quantities of superoxide anion radical are produced by newborn pig brain during bicuculline-induced seizures and that cyclooxygenase metabolism of arachidonic acid appears to be a major source.
J Cereb Blood Flow Metab 1989 Apr
PMID:Cerebral superoxide anion generation during seizures in newborn pigs. 292 Dec 92

Measurement of prostaglandin E2 (PGE2) in the ventriculocisternal perfusate of the halothane anesthetized, artificially ventilated cat has revealed low but measurable levels of the prostanoid (64 +/- 5 pg/min). Administration of pentamethylenetetrazole (PTZ) resulted in a rapid appearance of paroxysmal bursting, the magnitude and duration of which was dose dependent. During the 30-min interval after seizure initiation, PGE2 secretion rates into the ventriculocisternal perfusate rose by five- to sevenfold. Though the initial rate of PGE2 secretion correlated closely with the initial magnitude of bursting, there were significant differences, viz. the time courses. Thus, after a low dose of PTZ (200 mg/kg) the increase and return to normal of PGE2 secretion was time locked with the onset and offset of seizures. In contrast, after high doses of PTZ (250 mg/kg i.v.), seizure activity returned to near baseline by 90 min, while the levels of PGE2 secretion remained elevated for periods in excess of 150 min. Pretreatment with clonazepam (CLP: 3 mg/kg i.v. infusion) blocked seizures otherwise induced by PTZ (250 mg/kg) and the increase in PGE2 secretion. CLP administration 60 min after the initiation of seizures, blocked further seizure activity but did not alter the elevated secretion of PGE2. We thus believe these data jointly support the hypothesis that under intense paroxysmal bursting there is a change in neuronal state such that large stores of free fatty acids are available either because they have accumulated during the seizure because of a continued Ca2+ influx or the presence of large and continuing concentrations of Ca2+ accumulating in the cytosol secondary to energy failure.
J Cereb Blood Flow Metab 1989 Apr
PMID:CNS stimulation and PGE2 release. III. Pentamethylenetetrazole-induced seizures. 292 Dec 93

This study addresses the question of whether the cyclooxygenase inhibitors indomethacin and diclofenac and the glucocorticosteroid dexamethasone ameliorate neuronal necrosis following cerebral ischemia. In addition, since these drugs inhibit the production of prostaglandins and depress phospholipase A2 activity, respectively, the importance of free fatty acids (FFAs) on the development of ischemic neuronal damage was assessed. Neuronal damage was determined in the rat brain at 1 week following 10 min of forebrain ischemia. The cyclooxygenase inhibitors, whether given before or after ischemia, failed to alter the brain damage incurred. Animals given dexamethasone were divided into three groups and the drug was administered at a constant dosage of 2 mg/kg: (a) 2 days, 1 day, and 3 h intraperitoneally before (chronic pretreatment), (b) 3 h intraperitoneally before (acute pretreatment), and (c) 5 min intravenously and 6 h and 1 day intraperitoneally after (chronic posttreatment) induction of ischemia. Acute pretreatment did not affect the histopathological outcome. Chronic posttreatment of animals with dexamethasone ameliorated the damage inflicted on the caudate nucleus, but had no effect on other brain areas investigated. Unexpectedly, the chronic pretreatment aggravated the brain damage and caused seizures following ischemia. Histopathological data showed massive neuronal damage in these brains. The accumulation of FFA levels during ischemia was markedly suppressed, and the decrease in the energy charge was curtailed by chronic pretreatment with dexamethasone. However, brain glucose levels in control animals and lactic acid concentrations following 10 min of ischemia were significantly higher both in the cerebral cortex and in the hippocampus of dexamethasone-treated animals. These results suggest that aggravation of neuronal necrosis by chronic dexamethasone pretreatment could be ascribed to lactic acidosis due to hyperglycemia in combination with an action of dexamethasone on glucocorticoid receptors in the brain.
J Cereb Blood Flow Metab 1986 Aug
PMID:Chronic dexamethasone pretreatment aggravates ischemic neuronal necrosis. 309 61

The time course of changes in cortical tissue pH (pHi) and blood flow during cortical seizures in halothane-anesthetized cats was examined. The clearance of the molecular form of umbelliferone (Um) was used to estimate focal cortical blood flow (CBFu), whereas the ratio of the molecular to the ionic form of the molecule was used to concurrently calculate the local pHi. Resting pHi and flow in normocarbic animals was 7.116 +/- 0.008 and 46 +/- 8 ml/100 g/min, respectively. Respiratory induced alterations of PaCO2 over a range of 20-60 torr revealed a correlated change in pHi from 7.39 +/- 0.05 to 7.01 +/- 0.03 and a monotonic increase in the rate of Um clearance (slope 0.89 +/- 0.13 ml/100 g/min/torr). Focal electrical stimulation of the cortex resulted in a rapid vasodilation (50% dilation = 1-3 s) of pial arterioles and venules and an increase in Um clearance. pHi showed no significant change until around 10 s. The maximum fall in pHi occurred by 30-60 s (6.85 +/- 0.054). Longer intervals of stimulation (10 min) resulted in no further decline in pHi, but upon cessation of stimulation. pHi remained acidotic for poststimulation periods up to 10 min, with a mild but statistically significant acidosis being observed at 20 min. The absolute decline in pH observed following stimulation appeared to be closely regulated, as comparable levels following stimulation were observed during hypocarbia and hypercarbia. These observations thus suggest that pHi regulation during intense cortical activation may be considered in three phases: following the onset of activity, an initial acute regulation of pHi at control levels; an intracellular acidosis of around 6.8, which is closely regulated and which can be readily reversed upon termination of stimulation; and during continued stimulation, a change in state where in spite of no further change in pHi, the ability of the cortex to return to control pHi appears to be significantly impaired.
J Cereb Blood Flow Metab 1987 Jun
PMID:In vivo studies on intracellular pH, focal flow, and vessel diameter in the cat cerebral cortex: effects of altered CO2 and electrical stimulation. 310 71

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

We used serial positron emission tomography scans with [18F]2-deoxyglucose to study the effect of phenytoin on human cerebral glucose metabolism in 10 patients with seizure disorders. Local CMRglu for each patient was measured in 10 regions of interest. EEGs were performed during each procedure to match scans for state of consciousness and exclude data from scans with ictal activity. Serial scans without a drug change were performed in six control patients. Metabolic rates were significantly lower in two cortical regions while patients were taking phenytoin. No significant changes on repeat scan were seen in the control population. Measured across all regions of interest, metabolic rates were 13% higher when patients were off phenytoin (p less than 0.02).
J Cereb Blood Flow Metab 1986 Jun
PMID:Effect of phenytoin on human cerebral glucose metabolism. 348 72

Changes of interstitial fluid adenosine concentrations and effects of O2 supply on interstitial fluid adenosine were studied by the brain dialysis technique in the frontal cortex of newborn piglets subjected to bicuculline-induced seizures. The O2 supply was changed globally by changing MABP and locally by varying PO2 in the artificial CSF perfusing the dialysis cannula. Sagittal sinus blood flow (SSBF), cerebrovascular resistance (CVR), and CMRO2 were also examined in the same animals. Seizures increased interstitial fluid adenosine 7.9-fold (p less than 0.05) when ictal MABP was maintained at preictal level and perfusate PO2 was 24 mm Hg (group 1, n = 6). Interstitial fluid adenosine increased 11.8-fold (p less than 0.05) during seizures associated with moderate systemic hypotension and the low perfusate PO2 (group 2, n = 6). By contrast, seizures increased interstitial fluid adenosine three-fold (p less than 0.05) when perfusate PO2 was increased to 182 mm Hg and ictal MABP was maintained at preictal level (group 3, n = 8). When ictal MABP was elevated from the preictal level and the perfusate was rich in oxygen, seizures failed to increase interstitial fluid adenosine (group 4, n = 7). In groups 1 and 3, the increase in interstitial fluid adenosine during seizures was associated with significant increases in SSBF and CMRO2, as well as significant decreases in CVR. These data suggest that the increase in O2 supply during seizures in piglets did not match completely the increase in O2 demand and resulted in enhanced release of adenosine into the interstitial space.
J Cereb Blood Flow Metab 1987 Oct
PMID:Interstitial fluid adenosine and sagittal sinus blood flow during bicuculline-seizures in newborn piglets. 365 3

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

A quantitative technique utilising [14C]alpha-aminoisobutyric acid as a tracer was used to study cerebrovascular permeability in 22 Mongolian gerbils. Seven other animals were used to measure cerebral blood volumes. Global cerebral ischaemia was produced by temporary bilateral carotid artery occlusion (60 min) in 16 gerbils that were sacrificed at 1, 2, and 3 h following reperfusion. The blood-to-brain transfer constant was significantly increased after 2 h of reperfusion in the ischaemic zones and also in structures, like the cerebellum, not supplied by the carotid artery and not ischaemic during the vessel occlusion. The blood-brain barrier (BBB) alterations were coincident with the onset of ischaemia--induced seizures that were accompanied by sudden "spikes" of systemic blood pressure. Epilepsy may play an important role in the development of BBB damage in this ischaemic model, and this factor must be considered in the interpretation of BBB damage data in gerbils.
J Cereb Blood Flow Metab 1985 Mar
PMID:Regional blood-brain barrier permeability changes after restoration of blood flow in postischemic gerbil brains: a quantitative study. 397 15

The objective of the study was to estimate changes in extracellular pH (pHe) and intracellular pH (pHi) during seizures and in the recovery period following the arrest of seizure activity. Seizures of 5- and 20-min duration were induced in rats by fluorothyl added to the insufflated gas mixture, and recovery for 5, 15, and 45 min was instituted by withdrawal of the fluorothyl supply following 20 min of continuous seizures. Changes in pHe were measured by double-barreled, liquid ion-exchange pH microelectrodes, and in pHi by the CO2 method, following estimation of tissue PCO2 and extracellular fluid (ECF) volume. The animals were either normoxic or rendered moderately hypoxic (arterial PO2 40-50 mm Hg). Upon induction of seizures in normoxic animals, pHe decreased by a mean of 0.36 unit, the values being identical at 5 and 20 min. In moderate hypoxia, seizures sustained for 20 min were accompanied by a further fall in pHe (mean decrease 0.51 unit). The changes in pHe seemed mainly to reflect the nonionic diffusion of lactic acid from cells to the ECF (tissue lactate levels approximately 10 and 15 mumol g-1 during seizures in normoxic and hypoxic animals, respectively). However, the gradual fall in pHe attributable able to lactic acid production was preceded by rapid acidification, sometimes exceeding the steady-state values subsequently attained. This acidification was interpreted to reflect spreading depression and fast transcellular Na+/H+ exchange. Following cessation of seizure discharge, pHe normalized at a surprisingly slow rate, with some acidosis persisting even after 45 min. The difference between cerebrovenous and arterial PCO2 was reduced during seizures and increased in the recovery period, probably reflecting alterations in the blood flow/metabolic rate coupling. Impedance changes were slight, indicating only minor changes in ECF volume. Changes in pHi after 5 min of seizures ranged from 0.20 (normoxic animals) to 0.32 (hypoxic animals) unit, the pHi values after 20 min being 0.07-0.08 unit higher. The results suggest the regulation of pHi during ongoing seizures. Upon arrest of seizure activity, pHi rapidly increased to normal and subsequently to supranormal values. Postepileptic intracellular alkalosis occurred at a time when pHe was still reduced and in spite of the fact that tissue lactate values had not normalized. It is concluded that the rapid normalization of pHi and overt alkalosis were caused by the simultaneously occurring oxidation of lactate, with the removal of a stoichiometrical amount of H+, and the extrusion of H+ from cells, possibly via a Na+/H+ exchanger, the latter probably delaying normalization of pHe.
J Cereb Blood Flow Metab 1985 Mar
PMID:Extra- and intracellular pH in the brain during seizures and in the recovery period following the arrest of seizure activity. 397 23


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