ph der Gehirnrinde vom Kaninchen in situ w�hrend perakuter, totaler Isch�mie, reiner Anoxie und in der Erholung

Thorn, W.; Heitmann, R.

doi:10.1007/bf00363713

Cited by 56 publications

(13 citation statements)

References 20 publications

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“…Early work suggested that metabolic acidosis, caused by continued glycolysis, was responsible for the severe tissue disruption seen in the postmortem brain (Friede and van Houten, 1961). Descriptions of this phenomenon were supported by correlative evidence showing that, during cerebral ischemia, tissue pH drops and lactate concentrations soar (Thorn and Heitmann, 1954; Crowell and Kaufmann, 196 1 ;Ljunggren et al, 1974).These early findings made intuitive sense in that the brain, with its high metabolic rate, is a fertile territory for anaerobic acidosis. Oxygen lack in the brain triggers the Pasteur effect, stimulating glycolysis to keep Address correspondence and reprint requests to Dr. G. C. Siesjo, 1978).…”

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confidence: 90%

Evolving Concepts About the Role of Acidosis in Ischemic Neuropathology

Tombaugh

Sapolsky

1993

Journal of Neurochemistry

187

109

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Cerebral ischemia is one of the most common neurological insults. Many pathological events are undoubtedly triggered by ischemia, but only recently has it become accepted that ischemic cell injury arises from a complex interaction between multiple biochemical cascades. Tissue acidosis is a well established feature of ischemic brain tissue, but its role in ischemic neuropathology is still not fully understood. Within the last few years, new evidence has challenged the historically negative view of acidosis and suggests that it may play more of a beneficial role than previously thought. This review reintroduces the concept of acidosis to ischemic brain injury and presents some new perspectives on its neuroprotective potential. Key Words: Ischemia-infarction-Lactic acidosis-Excitotoxicity-Hippocampus-Selective neuronal necrosis -Energy metabolism. Experimental work aimed at understanding ischemic brain injury has highlighted numerous biochemical events that may mediate cell damage. Among these, tissue acidosis has received considerable attention. The history of the acidotic concept in ischemia research forms somewhat of an arch. A number of decades ago, cerebral acidosis was shown first to be a correlate of gross ischemic brain damage and was viewed later as a cause. At the height of interest in this topic, acidosis was considered among the principal mechanisms by which ischemic damage occurs (Myers, 1979;Siesjo, 1988~). Even so, it was clear that "cerebral ischemia" was not a single disease but any insult that involved a partial or complete reduction in cerebral blood flow. Various animal models of both focal and global ischemia have been widely used to study ischemic injury, but the question of whether tissue acidosis satisfactorily explains or even contributes to all forms of ischemic brain injury has never been formally addressed.Though acidosis is generally believed to underlie cerebral infarction, mounting evidence has suggested that acidosis does not contribute to the selective neuronal necrosis that occurs after transient ischemia or in the penumbra of developing infarcts. Not surprisingly, the earlier bias toward acidosis as a neurotoxic mechanism has waned. In this review, we briefly examine the evolution of the acidosis concept. We then focus on a recent and surprising series of in vitro observations suggesting that moderate acidosis may actually play a neuroprotective role during ischemia. We then discuss a striking and paradoxical implication of these data regarding the time course and possible mediators of selective neuronal injury following ischemia. THE TRADITIONAL BELIEF IN THE ACIDOTIC ROUTE OF ISCHEMIC DAMAGESupported by varying degrees of experimental evidence, many distinct mechanisms have been proposed to explain ischemic brain injury; of these, the concept of acidotic damage is perhaps the oldest. Early work suggested that metabolic acidosis, caused by continued glycolysis, was responsible for the severe tissue disruption seen in the postmortem brain (Friede and van Houten, 1961). D...

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confidence: 90%

Evolving Concepts About the Role of Acidosis in Ischemic Neuropathology

Tombaugh

Sapolsky

1993

Journal of Neurochemistry

187

109

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“…Changes in the extra-and intracellular H+ activity may alter ionic conductances, cell-to-cell coupling and the metabolic activity of brain cells (Siesjo & Sorensen, 1971;Roos & Boron, 1981; Moody, 1984;Hansen, 1985). In pathological states such as hypoxia, ischaemia and seizures, or even during prolonged activity, an acidosis is produced in the brain cells and in the interstitial fluid (Thorn & Heitmann, 1954;Siesjo, 1978;Ahmad & Loeschke, 1982;Kraig, Ferreira-Filho & Nicholson, 1983). This pH change in the various compartments ofthe brain may have an effect on the metabolic activity and the performance of nerve and glial cells.…”

Section: Introductionmentioning

confidence: 99%

The regulation of intracellular pH by identified glial cells and neurones in the central nervous system of the leech.

Deitmer

Schlue

1987

The Journal of Physiology

135

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SUMMARY1. Double-barrelled, neutral-carrier pH-sensitive micro-electrodes were used to measure the intracellular pH (pHi) and the pHi regulation of neuropile glial (n.g.) cells and of identified neurones of the leech Hirudo medicinalis.2. The distribution of H+ in the n.g. cells and in the neurones was found not to be in electrical equilibrium. The mean pHi ofthe n.g. cells was 6-87 + 0 13 (mean + S.D.of mean here and for all following data n = 27) in HEPES-buffered leech saline (pHo = 7 4) and 7418 + 0-19 (n = 13) in 2 % C02-11 mM-HC03--saline. The mean pHi was 7'28+0-1 (n = 20) in Retzius neurones and 7-32+0415 (n = 12) in noxious neurones in HEPES-buffered leech saline, and 7-20+0415 (n = 10) and 7-27 +016 (n = 6) in 2 % C02-1 1 mM-HC03--buffered saline in these two types of neurones, respectively.3. The cytoplasmic buffering power, as calculated by the change in pHi following the change from 2 % C02-11 mM-HC03-to 5 % C02-22 mM-HCO.-in the leech saline, was 20-30 mM/pH unit in the n.g. cells and between 12 and 33 mM/pH unit in the neurones.4. The recovery of pHi in n.g. cells from an experimentally induced acidification (addition and removal of 20 mm-NH4Cl) was dependent on the presence of external Na+. Independent of the buffer system used, pHi recovery was inhibited when external Na+ was exchanged by N-methyl-D-glucamine. Amiloride (2-3 mM) reduced the rate of pHi recovery by about 50 % in these n.g. cells.5. In CO2-HCO3--free saline, or in the presence of the anion exchange blocker 4-acetamido-4'-isothiocyanostilbene-2, 2'-disulphonic acid (SITS, 0 5 mM), pHi recovery from an acid load was often slowed by up to 50 % in n.g. cells. This suggests that there is a significant contribution of a HC03--dependent membrane transport to pHi regulation in n.g. cells.6. When a HEPES-buffered saline was exchanged by a 2 % C02-11 mM-HCO3-buffered saline, the pHi of n.g. cells increased by 0-31 pH units. This alkaline shift was reversible upon removal of the CO2-HC03-and was absent in the Na+-free saline. It was not inhibited by 1 mM-furosemide or by 0 5 mM-SITS. Successive addition of first Na+ and then CO2-HCO3-to an Na+-free HEPES-buffered saline produced two separate phases of intracellular alkalization, suggesting two different pHi regulation transport systems.J. W. DEITMER AND W.-R. SCHLUE 7. In sensory and Retzius neurones pHi recovery from acidification was also dependent on external Na+, both in the presence and in the absence of CO2-HC03-.The rate of pHi recovery was reversibly reduced by 2 mM-amiloride by up to 90 % in these neurones.8. In conclusion, bicarbonate buffer affects n.g. cell pHi differently from the way in which it affects neuronal pHi. The regulation of pHi depends on the presence of external Na+ in both n.g. cells and neurones. The experiments suggest the presence of an Na+-H+ exchange and a SITS-sensitive HCO3--and Na+-dependent acid extrusion mechanism across n.g. (and nerve cell) membranes and another, SITSinsensitive HC03-and Na+-dependent transport system only in n.g. cells.

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“…The subject of this case died of CO poisoning in a car: There was a hole in the floor of the car and the exhaust gas invaded the car through the broken muffler. The value of pH was 6.35 in the parietal, 6.32 in the frontal, 6.17 in the temporal lobes and 6.11 in the cerebellum. The brain showed macroscopical swelling and an increase of weight.…”

Section: Resultsmentioning

confidence: 88%

“…The curve for anoxic animals showed a more rapid rise than that for normal ones, and the acid production during oxygen deprivation was five times as great as that during sufficient supply of oxygen.5 Under the condition of ischemia, the pH went down rapidly during the first three minutes and the concentration of lactic acid increased. 6 It has been confirmed that the change of pH in the brain tissue is due to lactic acid produced. The important factors contributing to the final lactic acid concentration after death are the excessive acid in the brain at the time of death and the elevated blood sugar level.…”

Section: Discussionmentioning

confidence: 94%

Relationship between Acidity and Swelling in the Brain

Takahashi¹

1966

Tohoku J. Exp. Med.

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ph der Gehirnrinde vom Kaninchen in situ w�hrend perakuter, totaler Isch�mie, reiner Anoxie und in der Erholung

Cited by 56 publications

References 20 publications

Evolving Concepts About the Role of Acidosis in Ischemic Neuropathology

Evolving Concepts About the Role of Acidosis in Ischemic Neuropathology

The regulation of intracellular pH by identified glial cells and neurones in the central nervous system of the leech.

Relationship between Acidity and Swelling in the Brain

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