Monoamine metabolism during bicuculline-induced epileptic seizures in the rat

Calderini, G.; Carlsson, Arvid; ̈m, Carl-Henrik Nordstro

doi:10.1016/0006-8993(78)90031-8

Cited by 36 publications

(7 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results, and those observed in the present 20-min group, demonstrate that cAMP concentrations normalize during the first hour and increase again after 2 h of status epilepticus. Concerning the mechanism involved in the accumulation of CAMP, we tentatively conclude that it could reflect the perturbation of cerebral phosphorylation potential and the release of noradrenaline from storage sites (see Calderini et al, 1978), as well as dephosphorylation of AMP with release of adenosine, but the participation of other mediator(s) cannot be excluded at present.…”

Section: Changes In Cyclic Nucleotidesmentioning

confidence: 81%

Metabolic Changes in Cerebral Cortex, Hippocampus, and Cerebellum During Sustained Bicuculline‐Induced Seizures

Folbergrová

Ingvar

Siesjö

1981

Journal of Neurochemistry

139

View full text Add to dashboard Cite

The objective of the present experiments was to study metabolic correlates to the localization of neuronal lesions during sustained seizures. To that end, status epilepticus was induced by i.v. administration of bicuculline in immobilized and artificially ventilated rats, since this model is known to cause neuronal cell damage in cerebral cortex and hippocampus but not in the cerebellum. After 20 or 120 min of continuous seizure activity, brain tissue was frozen in situ through the skull bone, and samples of cerebral cortex, hippocampus, and cerebellum were collected for analysis of glycolytic metabolites, phosphocreatine (PCr), ATP, ADP, AMP, and cyclic nucleotides. After 20 min of seizure activity, the two "vulnerable" structures (cerebral cortex and hippocampus) and the "resistant" one (cerebellum) showed similar changes in cerebral metabolic state, characterized by decreased tissue concentrations of PCr, ATP, and glycogen, and increased lactate concentrations and lactate/pyruvate ratios. In all structures, though, the adenylate energy charge remained close to control. At the end of a 2-h period of status epilepticus, a clear deterioration of the energy state was observed in the cerebral cortex and the hippocampus, but not in the cerebellum. The reduction in adenylate energy charge in the cortex and hippocampus was associated with a seemingly paradoxical decrease in tissue lactate levels and with failure of glycogen resynthesis (cerebral cortex). Experiments with infusion of glucose during the second hour of a 2-h period of status epilepticus verified that the deterioration of tissue energy state was partly due to reduced substrate supply; however, even in animals with adequate tissue glucose concentrations, the energy charge of the two structures was significantly lowered. The cyclic nucleotides (cAMP and cGMP) behaved differently. Thus, whereas cAMP concentrations were either close to control (hippocampus and cerebellum) or moderately increased (cerebral cortex), the cGMP concentrations remained markedly elevated throughout the seizure period, the largest change being observed in the cerebellum. It is concluded that although the localization of neuronal damage and perturbation of cerebral energy state seem to correlate, the results cannot be taken as evidence that cellular energy failure is the cause of the damage. Thus, it appears equally probable that the pathologically enhanced neuronal activity (and metabolic rate) underlies both the cell damage and the perturbed metabolic state. The observed changes in cyclic nucleotides do not appear to bear a causal relationship to the mechanisms of damage.

show abstract

Section: Changes In Cyclic Nucleotidesmentioning

confidence: 81%

Metabolic Changes in Cerebral Cortex, Hippocampus, and Cerebellum During Sustained Bicuculline‐Induced Seizures

Folbergrová

Ingvar

Siesjö

1981

Journal of Neurochemistry

139

View full text Add to dashboard Cite

show abstract

“…However, the link between GHB-induced epileptogenesis and striatal dopamine is a tenuous one, since GHB is known to directly activate dopamine neurones in the nigrostriatal projection. By contrast, bicuculline seizures lead to a functional hypoactivity of dopamine neurones (Calderini et al, 1978).…”

Section: Effects Of Chemoconvulsantsmentioning

confidence: 96%

“…Various strains of rat have been inbred to perpetuate their proclivity for spontaneous epilepsy. One such genetically defined double mutant, created by cross-breeding zitter homozygotes with tremor heterozygotes, was shown by Hara et al (1993) to have a diminished concentration and turnover of dopamine in the striatum Lewis et al, 1987Stock et al, 1983F a j o and Blackwood, 1978Wilkison and Halpern, 1979Rada and Hernandez, 1990Blackwood, 1981Mintz et al, 1987, 1992Kant et al, 1980Ohmori et al, 1992Ashton et al, 1980Gee et al, 1980Csernansky et al, 1988aGelbard and Applegate, 1994Janowsky et al, 1991Gee et al, 1980El-Hamdi et al, 1992McMillen and Isaac, 1978Ray and Poddar, 1985Yokoi et al, 1986Calderini et al, 1978El-Etri et al, 1993Cavalheiro et al, 1991, 1994Al-Tajir and Starr, 1993Al-Tajir and Starr, 1993El-Etri et al, 1993Fosbraey et al, 1990Glisson et al, 1974Fernando et al, 1986Baran et al, 1989Brazsko et al, 1981Sperk et al, 1983Arias et al, 1990Beas-Zarate et al, 1985Dailey et al, 1991Zis et al, 1991Maitre et al, 1990Roth, 1976Ali et al, 1990…”

Section: Nonseizing Animalsmentioning

confidence: 99%

The role of dopamine in epilepsy

Starr

1996

Synapse

241

157

View full text Add to dashboard Cite

The clinical benefits of dopamine agonists in the management of epilepsy can be traced back over a century, whilst the introduction of neuroleptics into psychiatry practice 40 years ago witnessed the emergence of fits as a side effect of dopamine receptor blockade. Epidemiologists noticed a reciprocal relationship between the supposed dopaminergic overactivity syndrome of schizophrenia and epilepsy, which came to be regarded as a dopamine underactivity condition. Early pharmacological studies of epilepsy employed nonselective drugs, that often did not permit dopamine's antiepileptic action to be clearly dissociated from that of other monoamines. Likewise, the biochemical search for genetic abnormalities in brain dopamine function, as predeterminants of spontaneous epilepsy, proved largely inconclusive. The discovery of multiple dopamine receptor families (D1 and D2), mediating opposing influences on neuronal excitability, heralded a new era of dopamine‐epilepsy research. The traditional anticonvulsant action of dopamine was attributed to D2 receptor stimulation in the forebrain, while the advent of selective D1 agonists with proconvulsant properties revealed for the first time that dopamine could also lower the seizure threshold from the midbrain. Whilst there is no immediate prospect of developing D2 agonists or D1 antagonists as clinically useful antiepileptics, there is a growing awareness that seizures might be precipitated as a consequence of treating other neurological disorders with D2 antagonists (schizophrenia) or D1 agonists (parkinsonism). © 1996 Wiley‐Liss, Inc.

show abstract

“…27 Augmented transmitter release may also explain why seizures are accompanied by cellular uptake of Ca 2+ even though ATP concentrations are close to normal, and extracellular K + does not reach the threshold value of close to 15 umol. 237 Since noradrenaline and adenosine are known activators of membrane-bound adenylate cyclases, the expected result is accumulation of cyclic AMP (cAMP).…”

Section: Metabolic' Cascadesmentioning

confidence: 99%

Cerebral circulation and metabolism

Siesjö¹

1984

Journal of Neurosurgery

501

133

View full text Add to dashboard Cite

Recent developments in the field of cerebral circulation and metabolism are reviewed, with emphasis on circulatory and metabolic events that have a bearing on brain damage incurred in ischemia. The first part of the treatise reviews aspects of cerebral metabolism that provide a link to the coupling of metabolism and blood flow, notably those that lead to a perturbation of cellular energy state, ionic homeostasis, and phospholipid metabolism. In the second part, attention is focused on the derangement of energy metabolism and its effects on ion fluxes, acid-base homeostasis, and lipid metabolism. It is emphasized that gross brain damage, involving edema formation and infarction, is enhanced by tissue acidosis, and that neuronal damage, often showing a pronounced selectivity in localization, appears related to a disturbed Ca2+ homeostasis, and to Ca2+-triggered events such as lipolysis and proteolysis.

show abstract

Monoamine metabolism during bicuculline-induced epileptic seizures in the rat

Cited by 36 publications

References 16 publications

Metabolic Changes in Cerebral Cortex, Hippocampus, and Cerebellum During Sustained Bicuculline‐Induced Seizures

Metabolic Changes in Cerebral Cortex, Hippocampus, and Cerebellum During Sustained Bicuculline‐Induced Seizures

The role of dopamine in epilepsy

Cerebral circulation and metabolism

Contact Info

Product

Resources

About