Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury

Restricted access

✓ An increase in extracellular K+ concentration ([K+]e) of the rat hippocampus following fluid-percussion concussive brain injury was demonstrated with microdialysis. The role of neuronal discharge was examined with in situ administration of 0.1 mM tetrodotoxin, a potent depressant of neuronal discharges, and of 0.5 to 20 mM cobalt, a blocker of Ca++ channels. While a small short-lasting [K+]e increase (1.40- to 2.15-fold) was observed after a mild insult, a more pronounced longer-lasting increase (4.28- to 5.90-fold) was induced without overt morphological damage as the severity of injury rose above a certain threshold (unconscious for 200 to 250 seconds). The small short-lasting increase was reduced with prior administration of tetrodotoxin but not with cobalt, indicating that neuronal discharges are the source of this increase. In contrast, the larger longer-lasting increase was resistant to tetrodotoxin and partially dependent on Ca++, suggesting that neurotransmitter release is involved. In order to test the hypothesis that the release of the excitatory amino acid neurotransmitter glutamate mediates this increase in [K+]e, the extracellular concentration of glutamate ([Glu]e) was measured along with [K+]e. The results indicate that a relatively specific increase in [Glu]e (as compared with other amino acids) was induced concomitantly with the increase in [K+]e. Furthermore, the in situ administration of 1 to 25 mM kynurenic acid, an excitatory amino acid antagonist, effectively attenuated the increase in [K+]e. A dose-response curve suggested that a maximum effect of kynurenic acid is obtained at a concentration that substantially blocks all receptor subtypes of excitatory amino acids. These data suggest that concussive brain injury causes a massive K+ flux which is likely to be related to an indiscriminate release of excitatory amino acids occurring immediately after brain injury.

Article Information

Dr. Katayama is a Visiting Professor in Continuum on leave from the Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.

Address reprint requests to: David A. Hovda, Ph.D., Division of Neurosurgery, UCLA School of Medicine, CHS 74-140, University of California, Los Angeles, California 90024.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    A: Relationship between the injury severity and maximum levels of [K+]d after concussive brain injury in Group I rats that completely recovered from apnea within a short period of respiratory support. Results for control rats subjected to sham injury are also plotted. The [K+]d is expressed by a ratio (mean ± standard error of the mean) to baseline (average for 5-minute preinjury period). The curve represents a power analysis of best fit. B: Changes in [K+]d following concussive brain injury in Group Ia (lower graph) and Ib (upper graph) animals. The injury was administered at time zero. Each symbol represents the [K+]d of a 1-minute fraction located at a midpoint of the period in which the fraction was collected. Perfusion rate: 5.0 µl/min. A delay in response for the initial 1 minute is due to 5.0 µl of dead space in the dialysis system.

  • View in gallery

    Changes in [K+]d after concussive brain injury. A: Results in 24 Group I rats (filled circles) that completely recovered from apnea within a short period of respiratory support. Results for nine rats with a small [K+]d increase (Group Ia, see Fig. 1) and 15 rats with a larger [K+]d increase (Group Ib, see Fig. 1) are plotted separately. A response observed in five rats with sham injury (open circles) is shown for comparison. * = p < 0.01, comparison with sham-injured rats, unpaired t-test. B: Results for three Group II rats (filled circles) that suffered fatal apnea outlasting the period of respiratory support. The response observed in the 15 Group Ia animals (open circles) is plotted for comparison. The injury was administered at time zero. See legend for Fig. 1.

  • View in gallery

    Effects of tetrodotoxin (0.1 mM) administered in situ through the dialysis probe on the increase in [K+]d after concussive brain injury (filled circles). A response observed with a control probe placed in the hippocampus of the same animal and perfused without tetrodotoxin (open circles) is plotted for comparison. A: A small [K+]d increase (subthreshold response) is induced by a relatively mild insult in five Group Ia rats (see Fig. 1). * = p < 0.01, paired t-test. B: A larger [K+]d increase (suprathreshold response) is induced by a relatively severe insult in seven Group Ib rats (see Fig. 1).

  • View in gallery

    Effects of cobalt chloride (10 mM) administered in situ through the dialysis probe on the increase in [K+]d after concussive brain injury (filled circles). A response observed with a control probe placed in the hippocampus of the same animal and perfused without tetrodotoxin (open circles) is plotted for comparison. A: The effect on the small [K+]d increase (subthreshold response) induced by a relatively mild insult in four Group Ia rats (see Fig. 1). B: The effect on larger [K+]d increase (suprathreshold response) is induced by a relatively severe insult in eight Group Ib rats (see Fig. 1). C: A dose-relationship of cobalt concentration and the suprathreshold response of [K+]d to the injury. A minimum of four animals was used for each concentration. The [K+]d response (net increase in [K+]d) in the presence of cobalt is expressed as a percentage of the control response in each animal (mean ± standard error of the mean). * = p < 0.01, paired t-test.

  • View in gallery

    Changes in [K+]d (A) and [Glu]d (B) after concussive brain injury in four rats that completely recovered from apnea within a short period of respiratory support (Group Ia). Changes in the extracellular concentration of serine are also shown for comparison. The injury is administered at time zero. The [K+]d and [Glu]d are expressed by a ratio (mean ± standard error of the mean) to a 5-minute preinjury baseline measurement (see Table 4 and text). Each symbol and bar represents [K+]d and [Glu]d, respectively, for the 1-minute period at the midpoint in time during which the fraction was taken. The perfusion rate is 5.0 µl/min. A delay in response for the initial 1 minute is due to a dead space (5.0 µl) in the dialysis system. * = p < 0.05, as compared to the preinjury baseline, paired t-test.

  • View in gallery

    A: Effects of kynurenic acid (KYN) administered in situ through the dialysis probe on the increase in [K+]d after concussive brain injury in nine rats. Filled circles represent the test probe perfused with kynurenic acid (10 mM), open circles represent the control probe perfused with vehicle alone. [K+]d is expressed by a ratio (mean ± standard error of the mean) to the 5-minute preinjury baseline (see legend for Fig. 5 also). B: A dose-response relationship of concentration of kynurenic acid and the response of [K+]d to the injury. A minimum of four animals was used for each concentration. The [K+]d response (net increase in [K+]d) in the presence of kynurenic acid is expressed as a percentage of the control response observed in each animal (mean ± standard error of the mean). * = p < 0.01, paired t-test.

References

1.

Astrup JRehncrona SSiesjo BK: The increase in extracellular potassium concentration in the ischemic brain in relation to the preischemic functional activity and cerebral metabolic rate. Brain Res 199:1611741980Astrup J Rehncrona S Siesjo BK: The increase in extracellular potassium concentration in the ischemic brain in relation to the preischemic functional activity and cerebral metabolic rate. Brain Res 199:161–174 1980

2.

Ballanyi KGrafe PBruggenlate GT: Ion activities and potassium uptake mechanisms of glial cells in guinea-pig olfactory cortex slices. J Physiol 382:1591741987Ballanyi K Grafe P Bruggenlate GT: Ion activities and potassium uptake mechanisms of glial cells in guinea-pig olfactory cortex slices. J Physiol 382:159–174 1987

3.

Becker DP: Brain acidosis in head injury: a clinical trial in Becker DPPovlishock JT (eds): Central Nervous System Trauma Status Report. Richmond: Byrd Press1985 pp 229242Becker DP: Brain acidosis in head injury: a clinical trial in Becker DP Povlishock JT (eds): Central Nervous System Trauma Status Report. Richmond: Byrd Press 1985 pp 229–242

4.

Becker DP: Injury to the head and spine in Wyngarden JBSmith LHPlum F (eds): Cesil Textbook of Medicineed 18. Philadelphia: WB Saunders1985 pp 21702177Becker DP: Injury to the head and spine in Wyngarden JB Smith LH Plum F (eds): Cesil Textbook of Medicine ed 18. Philadelphia: WB Saunders 1985 pp 2170–2177

5.

Becker DPJenkins LWRabow L: The pathophysiology of head trauma in Miller TARowlands BJ (eds): The Physiological Basis of Modern Surgical Care. St Louis: CV Mosby1987 pp 763788Becker DP Jenkins LW Rabow L: The pathophysiology of head trauma in Miller TA Rowlands BJ (eds): The Physiological Basis of Modern Surgical Care. St Louis: CV Mosby 1987 pp 763–788

6.

Benveniste HDrejer JSchousboe Aet al: Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem 43:136913741984Benveniste H Drejer J Schousboe A et al: Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem 43:1369–1374 1984

7.

Choi DW: Ionic dependence of glutamate neurotoxicity. J Neurosci 7:3693791987Choi DW: Ionic dependence of glutamate neurotoxicity. J Neurosci 7:369–379 1987

8.

Choi DWKoh JYPeters S: Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonist. J Neurosci 8:1851961988Choi DW Koh JY Peters S: Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonist. J Neurosci 8:185–196 1988

9.

Collins RC: Selective vulnerability of brain. New insights from the excitatory synapse. Metab Brain Dis 1:2312401986Collins RC: Selective vulnerability of brain. New insights from the excitatory synapse. Metab Brain Dis 1:231–240 1986

10.

Cotman CWInverson LL: Excitatory amino acids in the brain — focus on NMDA receptors. Trends Neurosci 10:2632651987Cotman CW Inverson LL: Excitatory amino acids in the brain — focus on NMDA receptors. Trends Neurosci 10:263–265 1987

11.

Delgado JMRDefeudis FVRoth RHet al: Dialytrode for long-term intracerebral perfusion in awake monkeys. Arch Int Pharmacodyn Ther 198:9121971Delgado JMR Defeudis FV Roth RH et al: Dialytrode for long-term intracerebral perfusion in awake monkeys. Arch Int Pharmacodyn Ther 198:9–12 1971

12.

Denny-Brown DRussell WR: Experimental cerebral concussion. Brain 64:931641941Denny-Brown D Russell WR: Experimental cerebral concussion. Brain 64:93–164 1941

13.

DeSalles AAFJenkins LWAnderson RLet al: Extracellular potassium activity following concussion. A microelectrode study in the cat. Soc Neurosci Abstr 12:9671986DeSalles AAF Jenkins LW Anderson RL et al: Extracellular potassium activity following concussion. A microelectrode study in the cat. Soc Neurosci Abstr 12:967 1986

14.

DeWitt DSJenkins LWWei EPet al: The effects of fluid-percussion brain injury on regional cerebral blood flow and pial arteriolar diameter. J Neurosurg 64:7877941986DeWitt DS Jenkins LW Wei EP et al: The effects of fluid-percussion brain injury on regional cerebral blood flow and pial arteriolar diameter. J Neurosurg 64:787–794 1986

15.

Dixon CELyeth BGPovlishock JTet al: A fluid percussion model of experimental brain injury in the rat. J Neurosurg 67:1101191987Dixon CE Lyeth BG Povlishock JT et al: A fluid percussion model of experimental brain injury in the rat. J Neurosurg 67:110–119 1987

16.

Drejer JBenveniste HDiemer NHet al: Cellular origin of ischemia-induced glutamate release from brain tissue in vivo and in vitro. J Neurochem 45:1451511985Drejer J Benveniste H Diemer NH et al: Cellular origin of ischemia-induced glutamate release from brain tissue in vivo and in vitro. J Neurochem 45:145–151 1985

17.

Duckrow RBLaManna JCRosenthal Met al: Oxidative metabolic activity of cerebral cortex after fluid-percussion head injury in the cat. J Neurosurg 54:6076141981Duckrow RB LaManna JC Rosenthal M et al: Oxidative metabolic activity of cerebral cortex after fluid-percussion head injury in the cat. J Neurosurg 54:607–614 1981

18.

Faden AIDemediuk PPanter SSet al: The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 244:7988001989Faden AI Demediuk P Panter SS et al: The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 244:798–800 1989

19.

Faden AILemke MSimon RPet al: N-methyl-D-aspartate antagonist MK801 improves outcome following traumatic spinal cord injury in rats: behavioral, anatomic and neurochemical studies. J Neurotrauma 5:33461988Faden AI Lemke M Simon RP et al: N-methyl-D-aspartate antagonist MK801 improves outcome following traumatic spinal cord injury in rats: behavioral anatomic and neurochemical studies. J Neurotrauma 5:33–46 1988

20.

Fisher RSPedley TAMoody WJet al: The role of extracellular potassium in hippocampal epilepsy. Arch Neurol 33:76831976Fisher RS Pedley TA Moody WJ et al: The role of extracellular potassium in hippocampal epilepsy. Arch Neurol 33:76–83 1976

21.

Ganong AHCotman CW: Kynurenic acid and quinolinic acid act at N-methyl-D-aspartate receptors in the rat hippocampus. J Pharmacol Exp Ther 236:2932991986Ganong AH Cotman CW: Kynurenic acid and quinolinic acid act at N-methyl-D-aspartate receptors in the rat hippocampus. J Pharmacol Exp Ther 236:293–299 1986

22.

Ganong AHLanthorn THCotman CW: Kynurenic acid inhibits synaptic and acidic amino acid-induced responses in the rat hippocampus and spinal cord. Brain Res 273:1701741983Ganong AH Lanthorn TH Cotman CW: Kynurenic acid inhibits synaptic and acidic amino acid-induced responses in the rat hippocampus and spinal cord. Brain Res 273:170–174 1983

23.

Habiltz JJLangmoen IA: Excitation of hippocampal pyramidal cells by glutamate in the guinea-pig and rat. J Physiol (Lond) 325:3173311982Habiltz JJ Langmoen IA: Excitation of hippocampal pyramidal cells by glutamate in the guinea-pig and rat. J Physiol (Lond) 325:317–331 1982

24.

Hansen AJ: Effect of anoxia on ion distribution in the brain. Physiol Rev 65:1011481985Hansen AJ: Effect of anoxia on ion distribution in the brain. Physiol Rev 65:101–148 1985

25.

Hansen AJ: The extracellular potassium concentration in brain cortex following ischemia in hypo- and hyperglycemic rats. Acta Physiol Scand 102:3243291978Hansen AJ: The extracellular potassium concentration in brain cortex following ischemia in hypo- and hyperglycemic rats. Acta Physiol Scand 102:324–329 1978

26.

Hansen AJ: Extracellular potassium concentration in juvenile and adult rat brain cortex during anoxia. Acta Physiol Scand 99:4124201977Hansen AJ: Extracellular potassium concentration in juvenile and adult rat brain cortex during anoxia. Acta Physiol Scand 99:412–420 1977

27.

Harris RJRichards PGSymon Let al: pH, K+, and PO2 of the extracellular space during ischaemia of primate cerebral cortex. J Cereb Blood Flow Metab 7:5996041987Harris RJ Richards PG Symon L et al: pH K+ and PO2 of the extracellular space during ischaemia of primate cerebral cortex. J Cereb Blood Flow Metab 7:599–604 1987

28.

Hayes RLKatayama YYoung HFet al: Coma associated with flaccidity produced by fluid percussion concussion in the cat. Part 1: Is it due to depression of activity within the brainstem reticular formation? Brain Injury 2:31491988Hayes RL Katayama Y Young HF et al: Coma associated with flaccidity produced by fluid percussion concussion in the cat. Part 1: Is it due to depression of activity within the brainstem reticular formation? Brain Injury 2:31–49 1988

29.

Hayes RLLyeth BGJenkins LW: Neurochemical mechanisms of mild and moderate head injury: implications for treatment in Levin HSEisenberg HMBenton AL (eds): Mild Head Injury. New York: Oxford University Press1989 pp 5479Hayes RL Lyeth BG Jenkins LW: Neurochemical mechanisms of mild and moderate head injury: implications for treatment in Levin HS Eisenberg HM Benton AL (eds): Mild Head Injury. New York: Oxford University Press 1989 pp 54–79

30.

Heinemann ULux HD: Ceiling of stimulus induced rises in extracellular potassium concentration in the cerebral cortex of cat. Brain Res 120:2312491977Heinemann U Lux HD: Ceiling of stimulus induced rises in extracellular potassium concentration in the cerebral cortex of cat. Brain Res 120:231–249 1977

31.

Hotson JRSypert GWWard AA Jr: Extracellular potassium concentration changes during propagated seizures in neocortex. Exp Neurol 34:20261973Hotson JR Sypert GW Ward AA Jr: Extracellular potassium concentration changes during propagated seizures in neocortex. Exp Neurol 34:20–26 1973

32.

Hubschmann ORKornhauser D: Effects of intraparenchymal hemorrhage on extracellular cortical potassium in experimental head trauma. J Neurosurg 59:2892931983Hubschmann OR Kornhauser D: Effects of intraparenchymal hemorrhage on extracellular cortical potassium in experimental head trauma. J Neurosurg 59:289–293 1983

33.

Jenkins LWMoszynski KLyeth BGet al: The effect of serum hyperglycemia on the phenomenon of increased post-traumatic ischemic vulnerability. Soc Neurosci Abstr 14:6211988Jenkins LW Moszynski K Lyeth BG et al: The effect of serum hyperglycemia on the phenomenon of increased post-traumatic ischemic vulnerability. Soc Neurosci Abstr 14:621 1988

34.

Jenkins LWMoszynski KLyeth BGet al: Increased vulnerability of the mildly traumatized brain to cerebral ischemia. The use of controlled secondary ischemia as a research tool to identify common or different mechanisms contributing to mechanical and ischemic brain injury. Brain Res 477:2122241989Jenkins LW Moszynski K Lyeth BG et al: Increased vulnerability of the mildly traumatized brain to cerebral ischemia. The use of controlled secondary ischemia as a research tool to identify common or different mechanisms contributing to mechanical and ischemic brain injury. Brain Res 477:212–224 1989

35.

Jones BNGilligan JP: O-phthaldialdehyde precolumn derivatization and reversed phase high-performance liquid chromatography of polypeptide hydrolysates and physiological fluids. J Chromatogr 226:4714821983Jones BN Gilligan JP: O-phthaldialdehyde precolumn derivatization and reversed phase high-performance liquid chromatography of polypeptide hydrolysates and physiological fluids. J Chromatogr 226:471–482 1983

36.

Julian FJGoldman DE: The effects of mechanical stimulation on some electrical properties of axons. J Gen Physiol 46:2973131962Julian FJ Goldman DE: The effects of mechanical stimulation on some electrical properties of axons. J Gen Physiol 46:297–313 1962

37.

Katayama YCheung MKAlves Aet al: Ion fluxes and cell swelling after experimental traumatic brain injury: the role of excitatory amino acids in Hoff JTBetz AL (eds): Intracranial Pressure VII. New York: Springer-Verlag1989 pp 584588Katayama Y Cheung MK Alves A et al: Ion fluxes and cell swelling after experimental traumatic brain injury: the role of excitatory amino acids in Hoff JT Betz AL (eds): Intracranial Pressure VII. New York: Springer-Verlag 1989 pp 584–588

38.

Katayama YCheung MKGorman Let al: Increase in extracellular glutamate and associated massive ionic fluxes following concussive brain injury. Soc Neurosci Abstr 14:11541988Katayama Y Cheung MK Gorman L et al: Increase in extracellular glutamate and associated massive ionic fluxes following concussive brain injury. Soc Neurosci Abstr 14:1154 1988

39.

Katayama YGlisson JDBecker DPet al: Concussive head injury producing suppression of sensory transmission within the spinal cord in cats. J Neurosurg 63:971051985Katayama Y Glisson JD Becker DP et al: Concussive head injury producing suppression of sensory transmission within the spinal cord in cats. J Neurosurg 63:97–105 1985

40.

Katayama YTamura TKawamata Tet al: Concomitance and dependence of massive potassium flux to early glutamate release during cerebral ischemia in vivo. Soc Neurosci Abstr 15:3581989Katayama Y Tamura T Kawamata T et al: Concomitance and dependence of massive potassium flux to early glutamate release during cerebral ischemia in vivo. Soc Neurosci Abstr 15:358 1989

41.

Katzman R: Maintenance of a constant brain extracellular potassium. Fed Proc 35:124412471976Katzman R: Maintenance of a constant brain extracellular potassium. Fed Proc 35:1244–1247 1976

42.

Kubota MNakamura TSunami Ket al: [Changes in local cerebral glucose utilization, DC potential and potassium in various degrees of experimental head injury.] Neurotraumatology 10:2252311987 (Jpn)Kubota M Nakamura T Sunami K et al: [Changes in local cerebral glucose utilization DC potential and potassium in various degrees of experimental head injury.] Neurotraumatology 10:225–231 1987 (Jpn)

43.

Kuffler SW: Neuroglia cells: physiological properties and a potassium mediated effect of neuronal activity on the glial membrane potential. Proc R Soc Lond (B) 168:1201967Kuffler SW: Neuroglia cells: physiological properties and a potassium mediated effect of neuronal activity on the glial membrane potential. Proc R Soc Lond (B) 168:1–20 1967

44.

Leao AAP: Spreading depression of activity in the cerebral cortex. J Neurophysiol 7:3593901944Leao AAP: Spreading depression of activity in the cerebral cortex. J Neurophysiol 7:359–390 1944

45.

Lewis DVSchuete WH: NADH fluorescence and (K+) changes during hippocampal stimulation. J Neurophysiol 38:4054171975Lewis DV Schuete WH: NADH fluorescence and (K+) changes during hippocampal stimulation. J Neurophysiol 38:405–417 1975

46.

Lyeth BGDixon CHamm RJet al: Effects of anticholinergic treatment on transient behavioral suppression and physiological responses following concussive brain injury to the rat. Brain Res 448:88971988Lyeth BG Dixon C Hamm RJ et al: Effects of anticholinergic treatment on transient behavioral suppression and physiological responses following concussive brain injury to the rat. Brain Res 448:88–97 1988

47.

Lyeth BGJenkins LWHamm RJet al: Enduring short-term memory deficits in the absence of hippocampal cell death following moderate head injury in the rat. Soc Neurosci Abstr 13:12531987Lyeth BG Jenkins LW Hamm RJ et al: Enduring short-term memory deficits in the absence of hippocampal cell death following moderate head injury in the rat. Soc Neurosci Abstr 13:1253 1987

48.

Martins-Ferreira HDe Oliviera-Castro GStruchiner CJet al: Circulating spreading depression in isolated retina. J Neurophysiol 34:7737841974Martins-Ferreira H De Oliviera-Castro G Struchiner CJ et al: Circulating spreading depression in isolated retina. J Neurophysiol 34:773–784 1974

49.

Mayer MLWestbrook GL: Cellular mechanisms underlying excitotoxicity. Trends Neurosci 10:59611987Mayer ML Westbrook GL: Cellular mechanisms underlying excitotoxicity. Trends Neurosci 10:59–61 1987

50.

Mayevsky AChance B: Repetitive patterns of metabolic changes during cortical spreading depression of the awake rat. Brain Res 65:5295331974Mayevsky A Chance B: Repetitive patterns of metabolic changes during cortical spreading depression of the awake rat. Brain Res 65:529–533 1974

51.

Meyer JSKondo ANomura Fet al: Cerebral hemodynamics and metabolism following experimental head injury. J Neurosurg 32:3043191970Meyer JS Kondo A Nomura F et al: Cerebral hemodynamics and metabolism following experimental head injury. J Neurosurg 32:304–319 1970

52.

Miyazaki SNewlon PGGoldberg SJet al: Cerebral concussion suppresses hippocampal long-term potentiation (LTP) in rats in Hoff JTBetz AL (eds): Intracranial Pressure VII. New York: Springer-Verlag1989 pp 651653Miyazaki S Newlon PG Goldberg SJ et al: Cerebral concussion suppresses hippocampal long-term potentiation (LTP) in rats in Hoff JT Betz AL (eds): Intracranial Pressure VII. New York: Springer-Verlag 1989 pp 651–653

53.

Moghaddam BSchenk JOStewart WBet al: Temporal relationship between neurotransmitter release and ion flux during spreading depression and anoxia. Can J Physiol Pharmacol 54:110511101987Moghaddam B Schenk JO Stewart WB et al: Temporal relationship between neurotransmitter release and ion flux during spreading depression and anoxia. Can J Physiol Pharmacol 54:1105–1110 1987

54.

Moody WFutamachi KJPrince DA: Extracellular potassium activity during epileptogenesis. Exp Neurol 42:2482631974Moody W Futamachi KJ Prince DA: Extracellular potassium activity during epileptogenesis. Exp Neurol 42:248–263 1974

55.

Narahashi TMorore JWScott WR: Tetrodotoxin blockage of sodium conductance increase in lobster giant axons. J Gen Physiol 47:9659741964Narahashi T Morore JW Scott WR: Tetrodotoxin blockage of sodium conductance increase in lobster giant axons. J Gen Physiol 47:965–974 1964

56.

Nelson SRLowry OHPassonneau JV: Changes in energy reserves in mouse brain associated with compressive head injury in Caveness WFWalker AE (eds): Head Injury. Philadelphia: JB Lippincott1966 pp 444447Nelson SR Lowry OH Passonneau JV: Changes in energy reserves in mouse brain associated with compressive head injury in Caveness WF Walker AE (eds): Head Injury. Philadelphia: JB Lippincott 1966 pp 444–447

57.

Nicholls DGSihra TS: Synaptosomes process an exocytotic pool of glutamate. Nature 321:7727731986Nicholls DG Sihra TS: Synaptosomes process an exocytotic pool of glutamate. Nature 321:772–773 1986

58.

Nicholson CKraig RP: The behavior of extracellular ions during spreading depression in Zeuthen T (ed): The Application of Ion-Selective Electrodes. New York: Elsevier North-Holland1981 pp 217238Nicholson C Kraig RP: The behavior of extracellular ions during spreading depression in Zeuthen T (ed): The Application of Ion-Selective Electrodes. New York: Elsevier North-Holland 1981 pp 217–238

59.

Nilsson BNordström CH: Experimental head injury in the rat. Part 3: Cerebral blood flow and oxygen consumption after concussive impact acceleration. J Neurosurg 47:2622731977Nilsson B Nordström CH: Experimental head injury in the rat. Part 3: Cerebral blood flow and oxygen consumption after concussive impact acceleration. J Neurosurg 47:262–273 1977

60.

Nilsson BNordström CH: Rate of cerebral energy consumption in concussive head injury in the rat. J Neurosurg 47:2742811977Nilsson B Nordström CH: Rate of cerebral energy consumption in concussive head injury in the rat. J Neurosurg 47:274–281 1977

61.

Nilsson BPontén U: Experimental head injury in the rat. Part 2: Regional brain energy metabolism in concussive trauma. J Neurosurg 47:2522611977Nilsson B Pontén U: Experimental head injury in the rat. Part 2: Regional brain energy metabolism in concussive trauma. J Neurosurg 47:252–261 1977

62.

Olney JWPrice MTSamson Let al: The role of specific ions in glutamate neurotoxicity. Neurosci Lett 65:65711986Olney JW Price MT Samson L et al: The role of specific ions in glutamate neurotoxicity. Neurosci Lett 65:65–71 1986

63.

Orkand RK: Functional consequences of ionic changes resulting from electrical activity. Fed Proc 39:151515181980Orkand RK: Functional consequences of ionic changes resulting from electrical activity. Fed Proc 39:1515–1518 1980

64.

Paulson OBNewman EA: Does the release of potassium from astrocyte endfeet regulate cerebral blood flow. Science 237:8968981987Paulson OB Newman EA: Does the release of potassium from astrocyte endfeet regulate cerebral blood flow. Science 237:896–898 1987

65.

Perkins MNStone TW: An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid. Brain Res 247:1841871982Perkins MN Stone TW: An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid. Brain Res 247:184–187 1982

66.

Prince DALux HDNeher E: Measurements of extracellular potassium activity in cat cortex. Brain Res 50:4894951973Prince DA Lux HD Neher E: Measurements of extracellular potassium activity in cat cortex. Brain Res 50:489–495 1973

67.

Rosenthal MDuckrow RBLaManna JCet al: Consequences of cerebral injury on oxidative energy metabolism measured in situ in Grossman RGGildenberg PL (eds): Head Injury: Basic and Clinical Aspects. New York: Raven Press1982 pp 6978Rosenthal M Duckrow RB LaManna JC et al: Consequences of cerebral injury on oxidative energy metabolism measured in situ in Grossman RG Gildenberg PL (eds): Head Injury: Basic and Clinical Aspects. New York: Raven Press 1982 pp 69–78

68.

Rosenthal MSomjen G: Spreading depression, sustained potential shifts and metabolic activity of cerebral cortex of cats. J Neurophysiol 36:7397491973Rosenthal M Somjen G: Spreading depression sustained potential shifts and metabolic activity of cerebral cortex of cats. J Neurophysiol 36:739–749 1973

69.

Rothman SMOlney JW: Excitotoxicity and the NMDA receptor. Trends Neurosci 10:2993021987Rothman SM Olney JW: Excitotoxicity and the NMDA receptor. Trends Neurosci 10:299–302 1987

70.

Sanchez-Prieto JSihra TSNicholls DG: Characterization of the exocytotic release of glutamate from guineapig cerebral cortical synaptosomes. J Neurochem 49:58641987Sanchez-Prieto J Sihra TS Nicholls DG: Characterization of the exocytotic release of glutamate from guineapig cerebral cortical synaptosomes. J Neurochem 49:58–64 1987

71.

Somjen GGGiacchino JL: Potassium and calcium concentrations in interstitial fluid of hippocampal formation during paroxysmal responses. J Neurophysiol 53:109811081985Somjen GG Giacchino JL: Potassium and calcium concentrations in interstitial fluid of hippocampal formation during paroxysmal responses. J Neurophysiol 53:1098–1108 1985

72.

Sugaya ETakato MNoda Y: Neuronal and glia activity during spreading depression in cerebral cortex of cat. J Neurophysiol 38:8228411975Sugaya E Takato M Noda Y: Neuronal and glia activity during spreading depression in cerebral cortex of cat. J Neurophysiol 38:822–841 1975

73.

Sypert GWWard AA Jr: Changes in extracellular potassium activity during neocortical propagated seizures. Exp Neurol 45:19411974Sypert GW Ward AA Jr: Changes in extracellular potassium activity during neocortical propagated seizures. Exp Neurol 45:19–41 1974

74.

Takahashi HManaka SSano K: Changes in extracellular potassium concentration in cortex and brain stem during the acute phase of experimental closed head injury. J Neurosurg 55:7087171981Takahashi H Manaka S Sano K: Changes in extracellular potassium concentration in cortex and brain stem during the acute phase of experimental closed head injury. J Neurosurg 55:708–717 1981

75.

Tobiasz CNicholson C: Tetrodotoxin resistant propagation and extracellular sodium changes during spreading depression in rat cerebellum. Brain Res 241:3293331982Tobiasz C Nicholson C: Tetrodotoxin resistant propagation and extracellular sodium changes during spreading depression in rat cerebellum. Brain Res 241:329–333 1982

76.

Tossman UJonsson GUngerstedt U: Regional distribution and extracellular levels of amino acids in rat central nervous system. Acta Physiol Scand 127:5335451986Tossman U Jonsson G Ungerstedt U: Regional distribution and extracellular levels of amino acids in rat central nervous system. Acta Physiol Scand 127:533–545 1986

77.

Tsubokawa T: [The alternative of cerebral circulation and metabolism in concussion.] Neurol Surg 11:5635731983 Tsubokawa T: [The alternative of cerebral circulation and metabolism in concussion.] Neurol Surg 11:563–573 1983 (Jpn)(Jpn)

78.

Ungerstedt UHerrera-Manschitz MJungnelius Uet al: Dopamine synaptic mechanisms reflected in studies combining behavioral recordings and brain dialysis. Adv Dopamine Res 7:2192311982Ungerstedt U Herrera-Manschitz M Jungnelius U et al: Dopamine synaptic mechanisms reflected in studies combining behavioral recordings and brain dialysis. Adv Dopamine Res 7:219–231 1982

79.

Van Harreveld A: Two mechanisms for spreading depression in chicken retina. J Neurobiol 9:4194311978Van Harreveld A: Two mechanisms for spreading depression in chicken retina. J Neurobiol 9:419–431 1978

80.

Vyscocil FKriz NBures J: Potassium selective microelectrodes used for measuring the extracellular brain potassium during spreading depression and anoxic depolarization in rats. Brain Res 39:2552591973Vyscocil F Kriz N Bures J: Potassium selective microelectrodes used for measuring the extracellular brain potassium during spreading depression and anoxic depolarization in rats. Brain Res 39:255–259 1973

81.

Walker AEKolloros JJCase TJ: The physiological basis of concussion. J Neurosurg 1:1031661944Walker AE Kolloros JJ Case TJ: The physiological basis of concussion. J Neurosurg 1:103–166 1944

82.

Ward AA Jr: The physiology of concussion. Clin Neurosurg 12:951111966Ward AA Jr: The physiology of concussion. Clin Neurosurg 12:95–111 1966

83.

Westernink BHCDamsma GRollema Het al: Scope and limitations of in vivo brain dialysis: a comparison of its application to various neurotransmitter systems. Life Sci 41:176317761987Westernink BHC Damsma G Rollema H et al: Scope and limitations of in vivo brain dialysis: a comparison of its application to various neurotransmitter systems. Life Sci 41:1763–1776 1987

84.

Yang MSDeWitt DSBecker DPet al: Regional brain metabolite levels following mild experimental head injury in the cat. J Neurosurg 63:6176211985Yang MS DeWitt DS Becker DP et al: Regional brain metabolite levels following mild experimental head injury in the cat. J Neurosurg 63:617–621 1985

85.

Young WKoreh IYen V: Effects of sympathectomy on extracellular potassium activity and blood flow in experimental spinal cord contusion. Brain Res 253:1151251982Young W Koreh I Yen V: Effects of sympathectomy on extracellular potassium activity and blood flow in experimental spinal cord contusion. Brain Res 253:115–125 1982

TrendMD

Cited By

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 106 106 97
Full Text Views 230 230 71
PDF Downloads 83 83 25
EPUB Downloads 0 0 0

PubMed

Google Scholar