Intense Neuronal Activity Research Articles

Glycolytic and oxidative metabolic contributions to potassium ion transport in rat cerebral cortex.

Putative roles of glycolytic and oxidative metabolism in the removal of potassium ion from the extracellular space were examined in rat cerebral cortex. In response to direct electrical stimulation of the cerebral surface, the activity of extracellular potassium ion (Ko+) transiently increased. Inhibition of glycolysis with iodoacetate prolonged the time required for dissipation of the elevated Ko+. This slowing was most evident in the early period after stimulation, when Ko+ was relatively high. Levels of high-energy intermediates were unchanged by iodoacetate. In contrast, severe hypoxemia was without effect during the early phase of K+ removal but hypoxemia slowed the later restoration of the Ko+ baseline. These data demonstrate that the rapid removal of potassium ion from the extracellular space following intense neuronal activity is aided by the Embden-Myerhoff metabolic pathways and perhaps by direct coupling of ATP produced by glycolysis. We suggest that removal of potassium ion from the brain extracellular space depends on two ATP pools, one derived from oxidative phosphorylation, the other from glycolysis. The glycolytic ATP pool may be most involved in the early and rapid phase of potassium clearance; the oxidative ATP pool may be more associated with the second and slower phase of Ko+ clearance, and with the maintenance of the Ko+ baseline under 'resting' conditions.

Neuronal activity up-regulates astroglial gene expression.

Neuronal gene expression is known to be modulated by functional activity. This modulation is thought to play a key role in determining the differentiation of developing neurons and regulating the operation of mature neurons. Here we describe a regulation of astroglial gene expression by neuronal activity. We report that intense neuronal activity (electrically induced seizures) in rat hippocampus leads to rapid and dramatic increases in mRNA for glial fibrillary acidic protein (GFAP), an astroglia-specific intermediate filament protein. GFAP mRNA levels increased at sites of stimulation as well as in areas that were synaptically activated by the resultant seizures. When seizures were induced repetitively for many days, levels of GFAP mRNA remained chronically elevated. However, GFAP mRNA returned to control levels within a few days after the cessation of stimulation. The coupling between astroglial gene expression and neuronal activity may be a mechanism through which neuronal activity modulates the function of supporting cells that are responsible for regulating the extracellular microenvironment of the brain.

Epileptiform discharges induced by altering extracellular potassium and calcium in the rat hippocampal slice

During and after intense neuronal activity the concentration of extracellular potassium ([K +] 0) increases while the concentration of calcium ([Ca 2+] 0) decreases. The present study examined the effect of increased [K +] 0 alone, and with a parallel decrease in [Ca 2+] 0, on overall excitability, long-term potentiation (LTP), and the appearance of epileptiform discharges. [K +] 0 and [Ca 2+] 0 were varied over the range in which they fluctuate in vivo. Hippocampal slices were first equilibrated in a control artificial CSF containing 3.1 m M K + and 1.5 m M Ca 2+ and then reequilibrated in an identical solution except that the K + was increased to 3.55, 4, 5, 6, or 8 m M with and without a decrease in Ca 2+ to 1.0 m M. Raising [K +] 0 caused a leftward shift of input-output curves. Lowering [Ca 2+] 0 to 1.0 m M had no effect on the ability of [K +] 0 to shift the input-output curve to the left. LTP was not changed by increasing [K +] 0. Lowering [Ca 2+] 0 to 1.0 m M blocked LTP and increasing the [K +] 0 did not overcome this blockade. When [K +] 0 alone was altered, the [K +] 0s at which epileptiform bursts occurred 50% of the time were 5.6 and 7.6 m M for stimulus-locked and spontaneous bursting, respectively. The combination of decreased [Ca 2+] 0 and increased [K +] 0 made slices considerably more prone to epileptiform activity. In 1.0 m M [Ca 2+] 0, the [K +] 0 at which 50% of the slices showed stimulus-locked bursting was decreased to 3.6 m M while that for spontaneous discharges was 5.4 m M. The sensitivity of hippocampal slices to [K +] 0 and [Ca 2+] 0, and the synergistic actions of alterations of these ions, indicates that even small changes in the aggregate extracellular ionic milieu may be important in epileptogenesis.

Metabolic alterations underlying the development of hypermetabolic necrosis in the substantia nigra in status epilepticus.

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)

Release of endogenous Zn2+ from brain tissue during activity.

The role of divalent transition metal ions in neural function is poorly understood. In excess, these ions are associated with neurological disorders such as Wilson's disease, Pick's disease and epileptic seizures. We suggest that zinc ions, which are contained in nerve terminals, are extruded into the extracellular space during neuronal activity. Excessive levels of zinc may be released during intense neuronal activation, and contribute to the paroxysm and toxic damage observed. Zinc ions are contained in high concentrations in mossy fibres of the hippocampal formation, and it is the postsynaptic neurones of these fibres which are most susceptible to the toxic effects of kainic acid, a potent convulsant, or to chronic exposure to organometallic compounds. Here we demonstrate for the first time that Zn2+ is released into the extracellular space during excitation of hippocampal slices.

Abnormal scintiangiographic findings associated with seizure activity.

HomeRadiologyVol. 111, No. 1 PreviousNext ArticlesAbnormal Scintiangiographic Findings Associated with Seizure ActivityDonald L. Holmquest, Walton S. Launey, Jr.Donald L. Holmquest, Walton S. Launey, Jr.Author Affiliations Department of Nuclear Medicine Eisenhower Medical Center39000 Bob Hope Drive Palm Desert, Calif. 92260Donald L. HolmquestWalton S. Launey, Jr.Published Online:Apr 1 1974https://doi.org/10.1148/111.1.147MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In AbstractCerebral scintiangiography of 2 patients in status epilepticus showed intensive relative hyperperfusion of one hemisphere, although the static image remained normal. Following complete arrest of the seizure activity with appropriate therapy, cerebral blood flow returned to normal. This regional hyperperfusion is probably caused by increased local metabolic demands related to intense neuronal activity and should be differentiated from a neoplastic, vascular, or inflammatory lesion.Article HistoryAccepted: Oct 1973Published in print: Apr 1974 FiguresReferencesRelatedDetailsCited ByTransient computerised tomographic (CT) abnormalities following partial seizuresP. N.Jayakumar, Arun B.Taly, P. K.Mohan2009 | Acta Neurologica Scandinavica, Vol. 72, No. 1STATUS EPILEPTICUSTroy A.Payne, Thomas P.Bleck1997 | Critical Care Clinics, Vol. 13, No. 1Focal Cerebral Magnetic Resonance Changes Associated with Partial Status EpilepticusThomas R.Henry, IvoDrury, James A.Brunberg, Page B.Pennell, Paul E.McKeever, AhmadBeydoun1994 | Epilepsia, Vol. 35, No. 1Hyperdensity on CT After Seizure: A PitfallI.Hussain Bangash, Raymond S.Kandt, Bernard J.D'Souza, RalphHeinz1987 | Journal of Child Neurology, Vol. 2, No. 4Prolonged Focal Cerebral Edema Associated with Partial Status EpilepticusMicheleSammaritano, FrederickAndermann, DenisMelanson, Hanna M.Pappius, PeterCamfield, JeanAicardi, AllanSherwin1985 | Epilepsia, Vol. 26, No. 4Brain scintigraphy in the diagnosis of the sequelae of head traumaEdward B.Silberstein1983 | Seminars in Nuclear Medicine, Vol. 13, No. 2Cerebral Radionuclide AngiographyFred S.Mishkin1977 | Angiology, Vol. 28, No. 4Pediatric nuclear medicineHirschHandmaker, Jerold M.Lowenstein1975 | Current Problems in Pediatrics, Vol. 6, No. 2Todd's Paralysis: A Cerebrovascular Phenomenon?PHILIP R.YARNELL1975 | Stroke, Vol. 6, No. 3Recommended Articles RSNA Education Exhibits RSNA Case Collection Vol. 111, No. 1 Metrics Altmetric Score PDF download