scholarly journals Intracellular pH in the Brain following Transient Ischemia

1983 ◽  
Vol 3 (1) ◽  
pp. 109-114 ◽  
Author(s):  
Hideo Mabe ◽  
Photjanee Blomqvist ◽  
Bo K. Siesjö
Keyword(s):  
Creatine Kinase ◽  
Lactic Acid ◽  
Intracellular Ph ◽  
Adenine Nucleotides ◽  
Recovery Period ◽  
Transient Ischemia ◽  
Vessel Occlusion ◽  
Atp Production ◽  
Creatine Kinase Reaction ◽  
The Brain

The objective of the present study was to discover whether or not intracellular alkalosis develops in the brain in the recovery period following transient ischemia. Forebrain ischemia of 15-min duration was induced by four-vessel occlusion in rats, with recovery periods of 15, 60, and 180 min. Intracellular pH was derived both by the HCO3−–H2CO3 method and from the creatine kinase equilibrium. The ischemia was associated with energy failure and marked accumulation of lactic acid in the cerebral cortex. Recirculation brought about rapid rephosphorylation of adenine nucleotides and gradual normalization of lactic acid levels. After 15 min of recovery, the HCO3−–H2CO3 method indicated persisting acidosis, but the creatine kinase reaction did not. After 60 min, a shift of pH in the alkaline direction was demonstrated in both methods. This alkalosis had disappeared after 3 h of recovery. It is concluded that resumption of ATP production after ischemia is followed by a rapid rise in intracellular pH, which transiently increases above normal.

scholarly journals Extra- and Intracellular pH in the Brain during Seizures and in the Recovery Period following the Arrest of Seizure Activity

1985 ◽  
Vol 5 (1) ◽  
pp. 47-57 ◽  
Author(s):  
Bo K. Siesjö ◽  
Roger von Hanwehr ◽  
Görel Nergelius ◽  
Gunilla Nevander ◽  
Martin Ingvar
Keyword(s):  
Lactic Acid ◽  
Intracellular Ph ◽  
Seizure Activity ◽  
Lactic Acid Production ◽  
Recovery Period ◽  
Extracellular Fluid ◽  
The Difference ◽  
Lactate Levels ◽  
The Brain ◽  
Ph Microelectrodes

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 ∼ 10 and 15 μmol g−1 during seizures in normoxic and hypoxic animals, respectively). However, the gradual fall in pHe attributable 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.

scholarly journals Possible mechanisms underlying slow component of V̇o2 on-kinetics in skeletal muscle

2015 ◽  
Vol 118 (10) ◽  
pp. 1240-1249 ◽  
Author(s):  
Bernard Korzeniewski ◽  
Jerzy A. Zoladz
Keyword(s):  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Gradual Increase ◽  
Slow Component ◽  
Anaerobic Glycolysis ◽  
Atp Production ◽  
Slow Decrease ◽  
Muscle Ph ◽  
Creatine Kinase Reaction ◽  
Atp Supply

A computer model of a skeletal muscle bioenergetic system is used to study the background of the slow component of oxygen consumption V̇o2 on-kinetics in skeletal muscle. Two possible mechanisms are analyzed: inhibition of ATP production by anaerobic glycolysis by progressive cytosol acidification (together with a slow decrease in ATP supply by creatine kinase) and gradual increase of ATP usage during exercise of constant power output. It is demonstrated that the former novel mechanism is potent to generate the slow component. The latter mechanism further increases the size of the slow component; it also moderately decreases metabolite stability and has a small impact on muscle pH. An increase in anaerobic glycolysis intensity increases the slow component, elevates cytosol acidification during exercise, and decreases phosphocreatine and Pi stability, although slightly increases ADP stability. A decrease in the P/O ratio (ATP molecules/O2 molecules) during exercise cannot also be excluded as a relevant mechanism, although this issue requires further study. It is postulated that both the progressive inhibition of anaerobic glycolysis by accumulating protons (together with a slow decrease of the net creatine kinase reaction rate) and gradual increase of ATP usage during exercise, and perhaps a decrease in P/O, contribute to the generation of the slow component of the V̇o2 on-kinetics in skeletal muscle.

scholarly journals Changes in Extra- and Intracellular pH in the Brain during and following Ischemia in Hyperglycemic and in Moderately Hypoglycemic Rats

1986 ◽  
Vol 6 (5) ◽  
pp. 574-583 ◽  
Author(s):  
M. -L. Smith ◽  
R. von Hanwehr ◽  
B. K. Siesjö
Keyword(s):  
Lactic Acid ◽  
Intracellular Ph ◽  
Extracellular Ph ◽  
Forebrain Ischemia ◽  
Extracellular Acidosis ◽  
The Brain ◽  
Tissue Metabolites

Incomplete forebrain ischemia of 15-min duration was induced in rats made hyperglycemic or moderately hypoglycemic prior to ischemia. Tissue CO2 tension, CO2 content, labile tissue metabolites, and extracellular pH (pHe) were measured, and intracellular pH (pHi) was derived by calculation on the assumption that cerebral intracellular fluids can be lumped into one space. In hypoglycemic animals, mean tissue lactate content increased from 2 to 10 μmol g−1. Tissue CO2 content was virtually unchanged and the CO2 tension increased from ∼50 to ∼145 mm Hg. In hyperglycemic animals, tissue lactate content rose to 20 μmol g−1, and the CO2 content decreased by 25%, demonstrating that some CO2 was lost to the blood supplied by the remaining perfusion. Accordingly, tissue CO2 tension did not rise above 200 mm Hg. pHe was reduced in proportion to the amount of lactate accumulated, the values obtained in hypo- and hyperglycemic animals showing relatively little scatter (6.76 ± 0.03 and 6.25 ± 0.04, respectively). In hypoglycemic animals the extracellular HCO−3 concentration was virtually unchanged, demonstrating that any influx of lactic acid from the cells must have been accompanied by H+ efflux and/or HCO−3 influx via independent routes. In hyperglycemic animals [HCO−3]e fell by >10 μmol ml−1. In both groups [HCO−3]e was reduced during the first 5 min of recovery. Recovery of pHe was slower in hyper- than in hypoglycemic animals. During ischemia calculated pHi fell to 6.37 ± 0.04 and 5.95 ± 0.06 in hypo- and hyperglycemic animals, respectively. Differences in pHi were maintained for the first 15 min of recovery, but in both hypo- and hyperglycemic animals pHi had normalized after 30 min. It is concluded that preischemic hyperglycemia leads to a more pronounced intra- and extracellular acidosis than normo- and hypoglycemia, an acidosis that also resolves more slowly during recirculation.

scholarly journals Probable Causes of Alzheimer’s Disease

Sci ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 16
Author(s):  
James David Adams
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lactic Acid ◽  
Blood Brain Barrier ◽  
Transient Receptor Potential ◽  
Brain Barrier ◽  
Folate Intake ◽  
Blood Brain ◽  
Age Related ◽  
The Brain

A three-part mechanism is proposed for the induction of Alzheimer’s disease: (1) decreased blood lactic acid; (2) increased blood ceramide and adipokines; (3) decreased blood folic acid. The age-related nature of these mechanisms comes from age-associated decreased muscle mass, increased visceral fat and changes in diet. This mechanism also explains why many people do not develop Alzheimer’s disease. Simple changes in lifestyle and diet can prevent Alzheimer’s disease. Alzheimer’s disease is caused by a cascade of events that culminates in damage to the blood–brain barrier and damage to neurons. The blood–brain barrier keeps toxic molecules out of the brain and retains essential molecules in the brain. Lactic acid is a nutrient to the brain and is produced by exercise. Damage to endothelial cells and pericytes by inadequate lactic acid leads to blood–brain barrier damage and brain damage. Inadequate folate intake and oxidative stress induced by activation of transient receptor potential cation channels and endothelial nitric oxide synthase damage the blood–brain barrier. NAD depletion due to inadequate intake of nicotinamide and alterations in the kynurenine pathway damages neurons. Changes in microRNA levels may be the terminal events that cause neuronal death leading to Alzheimer’s disease. A new mechanism of Alzheimer’s disease induction is presented involving lactic acid, ceramide, IL-1β, tumor necrosis factor α, folate, nicotinamide, kynurenine metabolites and microRNA.

H+-linked transport of salicylic acid, an NSAID, in the human trophoblast cell line BeWo

2002 ◽  
Vol 282 (5) ◽  
pp. C1064-C1075 ◽  
Author(s):  
Akiko Emoto ◽  
Fumihiko Ushigome ◽  
Noriko Koyabu ◽  
Hiroshi Kajiya ◽  
Koji Okabe ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
Lactic Acid ◽  
Cell Line ◽  
Intracellular Ph ◽  
Trophoblast Cell ◽  
Monocarboxylate Transporter ◽  
Human Trophoblast ◽  
Inflammatory Drugs ◽  
Ph Dependent ◽  
Trophoblast Cell Line

We investigated the transport of salicylic acid and l-lactic acid across the placenta using the human trophoblast cell line BeWo. We performed uptake experiments and measured the change in intracellular pH (pHi). The uptakes of [14C]salicylic acid andl-[14C]lactic acid were temperature- and extracellular pH-dependent and saturable at higher concentrations. Both uptakes were also reduced by FCCP, nigericin, and NaN3. Various nonsteroidal anti-inflammatory drugs (NSAIDs) strongly inhibited the uptake of l-[14C]lactic acid. Salicylic acid and ibuprofen noncompetitively inhibited the uptake ofl-[14C]lactic acid. α-Cyano-4-hydroxycinnamate (CHC), a monocarboxylate transporter inhibitor, suppressed the uptake ofl-[14C]lactic acid but not that of [14C]salicylic acid. CHC also suppressed the decrease of pHi induced by l-lactic acid but had little effect on that induced by salicylic acid or diclofenac. These results suggest that NSAIDs are potent inhibitors of lactate transporters, although they are transported mainly by a transport system distinct from that for l-lactic acid.

Anoxia and adenosine induce increased cerebral blood flow rate in crucian carp

1994 ◽  
Vol 267 (2) ◽  
pp. R590-R595 ◽  
Author(s):  
G. E. Nilsson ◽  
P. Hylland ◽  
C. O. Lofman
Keyword(s):  
Blood Flow ◽  
Flow Rate ◽  
Crucian Carp ◽  
Blood Flow Rate ◽  
Fold Increase ◽  
Liver Glycogen ◽  
Glycolytic Flux ◽  
Brain Blood Flow ◽  
Atp Production ◽  
The Brain

The crucian carp (Carassius carassius) has the rare ability to survive prolonged anoxia, indicating an extraordinary capacity for glycolytic ATP production, especially in a highly energy-consuming organ like the brain. For the brain to be able to increase its glycolytic flux during anoxia and profit from the large liver glycogen store, an increased glucose delivery from the blood would be expected. Nevertheless, the effect of anoxia on brain blood flow in crucian carp has never been studied previously. We have used epireflection microscopy to directly observe and measure blood flow rate on the brain surface (optic lobes) during normoxia and anoxia in crucian carp. We have also examined the possibility that adenosine participates in the regulation of brain blood flow rate in crucian carp. The results showed a 2.16-fold increase in brain blood flow rate during anoxia. A similar increase was seen after topical application of adenosine during normoxia, while adenosine was without effect during anoxia. Moreover, superfusing the brain with the adenosine receptor blocker aminophylline inhibited the effect of anoxia on brain blood flow rate, clearly suggesting a mediatory role of adenosine in the anoxia-induced increase in brain blood flow rate.

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