Hydrogen ion buffering during complete brain ischemia

Kraig, Richard P.; Pulsinelli, William A.; Plum, Fred

doi:10.1016/0006-8993(85)91127-8

Cited by 105 publications

(74 citation statements)

References 34 publications

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“…In addition, animals were normoxic, normoglycemic, and had normal hematocrits and body temperatures. Brain physiologic variables (Table 2) (Kraig et al 1983(Kraig et al ,1985a(Kraig et al ,1985b(Kraig et al ,1986 (Siesjö 1985), should encourage others to apply similar measurements to areas of interest. Perhaps the most important aspect of the present combined electrode experiments is the speed in which changes in carbonic acid buffer species and ammonia buffer species can be measured.…”

Section: Resultsmentioning

confidence: 99%

“…al. 1983;Kraig et al 1985b) and the CO 2 semimicroelectrode (Kraig et al 1986), the electrode array was advanced so that the CO 2 electrode's active surface gently touched the pial surface. The H + -selective microelectrode was angled by about 20° from vertical and positioned so that it recorded from adjacent interstitial space 300 μm below the pial surface and immediately beneath the surface of the CO 2 electrode.…”

Section: Animal Preparation and Recordingmentioning

confidence: 99%

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Bicarbonate and ammonia changes in brain during spreading depression

Kraig¹,

Cooper²

1987

Can. J. Physiol. Pharmacol.

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An alkaline, followed by an acid-going transient, characterizes acid-base changes in the interstitial space during spreading depression in a variety of brain structures. In rat, such changes are associated with a significant rise in brain lactate content. How brain proton buffers behave during spreading depression is unknown. Techniques to significantly improve the response time of gas permeable membrane semnimicroelectrodes for carbon dioxide and ammonia are reported. Measurements with such electrodes, when coupled to measurements of hydrogen ion concentration (from microelectrodes), permit rapid changes to be determined in bicarbonate concentration or ammonia and ammonium ion concentration, respectively. Bicarbonate concentration fell from 30 ± 1 (n = 16) to 14 ± 1 mM (n = 16) during spreading depression. On the other hand, ammonia concentration rose from 2.3 ± 0.1 to 4.4 ± 0.3 μM (n = 17) while ammonium ion concentration rose from 116 ± 11 (n = 17) to 382 ± 30 μM (n = 17) during spreading depression. Bicarbonate changes probably reflect titration of brain bicarbonate stores by accumulated lactic acid. Similar physicochemical changes do not explain the rise in ammonia and ammonium ion concentrations. Instead, elevation of the latter can only result from an increase in ammonia content of the interstitial space.

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Section: Resultsmentioning

confidence: 99%

Section: Animal Preparation and Recordingmentioning

confidence: 99%

Bicarbonate and ammonia changes in brain during spreading depression

Kraig¹,

Cooper²

1987

Can. J. Physiol. Pharmacol.

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“…There is a possibility that the extracel lular space may be as acidotic as intracellular, but this situation is unlikely to occur as long as there is some blood flow. Also, studies using microelec trodes suggest an active mechanism to maintain pHE in the case of intracellular acidosis (Kraig et al, 1985;Harris et al, 1987). Therefore, acidotic pHt in acute stroke may suggest intact cell mem branes with intracellular acidosis induced by lactic acid production.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the ¹¹CO₂ Positron Emission Tomographic Method for Measuring Brain pH. II. Quantitative pH Mapping in Patients with Ischemic Cerebrovascular Diseases

Senda

Alpert²,

Mackay³

et al. 1989

J Cereb Blood Flow Metab

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Summar y : A practical method has been developed that, using II COZ and positron emission tomography (PET), computes and maps (a) "effective pH" (pH,), a weighted average of intra-and extracellular pH, and (b) "clearance" (K\), product of blood flow and llCOZ ex traction. This method, together with measurements of ce rebral blood flow (CBF) and oxygen extraction fraction (OEF), was applied to 12 patients with cerebral ischemia or stroke. The regional K\ was positively correlated with CBF (n = +0.78). The k\/CBF ratio, representing the extraction fraction ratio of llCOZ to H/50, was nega tively correlated with CBF (r = -0.54), suggesting that I leoz extraction decreases as flow increases. In five acute stroke patients within 2 days of onset, the injured cortex had lower CBF (20.6 mi/min/IOO g), higher OEF Brain pH is tightly regulated by physicochemical buffering, by metabolic breakdown and production of acids, and perhaps by active transport of H + or HC03 -. Such tight control is necessary at least in part because of the pH dependence of the activity of several enzymes involved in energy metabolism and Received March 13, 1989; revised June 5, 1989; accepted June 8, 1989 Address correspondence and reprint requests to Dr. N. M. Alpert at Division of Nuclear Medicine, Massachusetts General Hospital, Fruit Street, Boston , MA 02 114, U.S.A.Abbreviations used: ANOVA, analysis of variance; CBF, ce rebral blood flow; CBV, cerebral blood volume; CMR02 , cere bral metabolic rate of 02; CSF, cerebrospinal fluid; CT, com puted tomography; DMO, 5,5-dimethyl-2,4-oxazolidinedione; FWHM, full width at half-maximum; GLM , General Linear Model; OEF, oxygen extraction fraction; OM, orbitomeatal; PET, positron emission tomography; ROI, region of interest; TIA, transient ischemic attack. 859(78. 1 %), and lower pH, (6.96) than the contralateral cor tex (CBF = 41.4 mi/min/IOO g, OEF = 53.3%, pH, = 7.00), suggesting intracellular acidosis with intact cell membranes. In three stroke patients 5-8 days after onset, the injured cortex had higher CBF (60.9 mllmin/IOO g), lower OEF (32.0%), and higher pH, (7. 12) than the con tralateral cortex (CBF = 45.3 ml/min/IOO g, OEF = 58.0%, pH, = 7.06), which suggested an increase in ex tracellular volume compartment reflecting loss of cell membrane integrity. This method provides information on the regional tissue acid-base status and cell membrane integrity, which may be prognostic of tissue viability. Ke y Words: Brain pH-Positron emission tomography \\ COz-Stroke-Cerebral acid-base status-Hydrogen ion concentration .

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“…Indeed, the neurotoxicity of A␤ in vitro requires the presence of microglia, which are activated by this peptide [16,25,47]. In the CNS, astrocytes are important for maintaining homeostasis [6,18,21,28,37,48,49] and also have an important role in immune responses. For example, these cells can migrate in response to chemotactic stimuli and gather in areas of injury or inflammation.…”

Section: Introductionmentioning

confidence: 99%