Biomedical subjects

A Baethmann

Publications and source records attributed to A Baethmann.

At least 55 records · Page 3Linked to original sources

PubMed1999

Influence of platelet-activating factor on cerebral microcirculation in rats: part 2. Local application.

BACKGROUND AND PURPOSE: Platelet-activating factor (PAF) is involved in the development of secondary brain damage after ischemic and traumatic brain injury. On the basis of data from studies in peripheral organs, we hypothesized that PAF-mediated effects after cerebral injury could be secondary to alterations in cerebral microcirculation. METHODS: Changes in cerebral microcirculation focusing on leukocyte-endothelium interactions were quantified with the use of a closed cranial window model in Sprague-Dawley rats (n=33) by means of intravital fluorescence microscopy. The brain surface was superfused with PAF in concentrations from 10(-3) (n=3) to 10(-12) mol/L (n=6) for 20 minutes (5 mL/h). RESULTS: PAF 10(-4) mol/L (n=4) increased the number of rolling and adherent leukocytes in venules from 9.7+/-0.4 to 19.7+/-2.3 cells/100 mm. min (P=NS versus control) and from 2.2+/-0.5 to 4.3+/-0.7 cells/100 mm. min (P<0.05 versus control), respectively. Lower concentrations did not elicit leukocyte-endothelium interactions. Vessel diameters remained unchanged except for a transient increase of arteriolar diameters during superfusion with PAF 10(-4) and 10(-6) mol/L (n=6). Although only a limited area of the brain surface was exposed to PAF, the mediator induced a significant dose-dependent transitory arterial hypotension and caused irreversible circulatory shock at the high concentration (PAF 10(-3) mol/L). Arterial hypotension after administration of PAF 10(-3) mol/L could be attenuated by the intravenous pretreatment with the PAF antagonist WEB 2170BS. CONCLUSIONS: PAF, when locally released after brain injury, can penetrate the blood-brain barrier and induce systemic effects, including arterial hypotension. Its role as a mediator in the development of secondary brain damage seems, at least in the initial phase, not to be associated with disturbances of cerebral microcirculation or activation of leukocytes.

Animals↗

PubMed1999

Combination drug therapy and mild hypothermia: a promising treatment strategy for reversible, focal cerebral ischemia.

BACKGROUND AND PURPOSE: Hypothermia has been suggested to be the most potent therapeutic approach to reduce experimental ischemic brain injury identified to date, and mild hypothermia is increasingly used for neuroprotection during neurovascular surgery. We have recently demonstrated that combined administration of tirilazad mesylate and magnesium provides for an overall enhanced neuroprotective effect. The present study was designed to determine whether the efficacy of mild hypothermia (33 degrees C) can be increased by combination pharmacotherapy with tirilazad and magnesium (MgCl(2)). METHODS: Forty Sprague-Dawley rats were subjected to transient, middle cerebral artery occlusion and were randomly assigned to 1 of 4 treatment arms (n=10 each): (1) normothermia+vehicle, (2) normothermia+tirilazad+MgCl(2), (3) hypothermia+vehicle, or (4) hypothermia+tirilazad+MgCl(2). Cortical blood flow was monitored by a bilateral laser-Doppler flowmeter, and the electroencephalogram was continuously recorded. Functional deficits were quantified by daily neurological examinations. Infarct volume was assessed after 7 days. RESULTS: Tirilazad+MgCl(2), hypothermia, and hypothermia+tirilazad+MgCl(2) reduced total infarct volume by 56%, 63%, and 77%, respectively, relative to controls. In animals treated with both hypothermia and combination pharmacotherapy, cortical infarction was almost completely abolished (-99%), and infarct volume in the basal ganglia was significantly reduced by 55%. In addition, this treatment provided for the best electrophysiological recovery and functional outcome. CONCLUSIONS: The neuroprotective efficacy of hypothermia can be increased by pharmacological antagonism of excitatory amino acids and free radicals by using clinically available drugs. This treatment strategy could be of great benefit when applied during temporary artery occlusion in cerebrovascular surgery.

Animals↗

PubMed1999

Why have recent trials of neuroprotective agents in head injury failed to show convincing efficacy? A pragmatic analysis and theoretical considerations

An overview of the results of recent trials of neuroprotective agents in head injury is presented. None of the trials showed efficacy in the general population of patients with a severe head injury. A critical analysis of the possible reasons for this failure is given. Specific attention is focused on the heterogeneity of the patient population, the importance of baseline prognostic indicators, and the problems caused by the distribution of outcome and the dichotomization of these outcomes in the Glasgow Outcome Scale. Recommendations are presented for consideration in the design and analysis of future trials in head injury.

Journal Article↗

PubMed1998

Prospective analysis of patient management in severe head injury.

Severe head injury with and without peripheral trauma is the most frequent cause of death and of severe disability up to 45 years. Outcome is determined by two major factors, the extent and nature of the irreversible primary brain damage, and the evolving secondary sequelae, which contrary to the former are responsive in principle to therapeutic intervention. An improvement of outcome from severe head injury can be expected only from an increased efficiency of the measures to prevent secondary brain damage. A research consortium "Neurotrauma" was formed by the University of Munich in collaboration with almost all city hospitals in Munich, Augsburg, Murnau, Ingolstadt, Vogtareuth and Southern Bavaria, providing care for neurotrauma patients. These hospitals together with the associated organizations carry out a system analysis on the management, logistics, organization, patient referral, etc. In severe head injury. Data acquisition is e.g. also concerned with outcome-relevant time periods of emergency care measures in the pre-clinical phase until hospital admission, conclusion of diagnostic procedure, and of the initial clinical care. Current results and experiences with establishment of this comprehensive research organization are presented, where no less than 31 hospitals. Institutions and organizations, and a study group of more than 40 physicians, students and statisticians are collaborating. Emerging data appear to be suitable to further improve pertinent aspects of the patient management as a basis to lower the incidence of secondary brain damage from severe head injury.

Adult↗

PubMed1998

Relevance of calcium homeostasis in glial cell swelling from acidosis.

Tissue acidosis from trauma or ischemia induces cytotoxic brain edema, mainly affecting astrocytes. In vitro, lactacidosis induces a dose-dependent swelling of glial cells. Activation of membrane transporters and channels, also involved in regulation of intracellular pH (pHi), has been identified as underlying mechanism, although details are poorly understood. We have currently studied whether Ca(2+)-ions play a role in acidosis-induced glial swelling and the associated intracellular acidification. The medium pH of a cell suspension (C6 glioma) was lowered from control (7.4) to 6.2 by lactic acid. Cell volume (CV) and pHi were assessed by flow cytometry. During acidosis in normal medium (2.2 mM Ca2+) CV reached a maximum of 125.1%. In a calcium-free medium swelling from acidosis was inhibited by 74%, while additional buffering of intracellular calcium (Ca2+i) by BAPTA-AM had no further effect. Buffering of Ca2+i alone did not affect the CV increase from acidosis at all. pHi which is decreasing during acidosis was not influenced by the above modifications. The present experiments indicate that lactacidosis-induced glial swelling depends on the presence of extracellular Ca(2+)-ions, while alterations of Ca2+i do not seem to be involved.

Acid-Base Equilibrium↗

PubMed1998

Resolution of experimental vasogenic brain edema at different intracranial pressures.

Resolution of vasogenic brain edema was examined using the infusion edema model in rabbits. Texas Red-albumin (MW 66,000 D) and sodium fluorescein (MW 376 D) dissolved in artificial cerebrospinal fluid (aCSF) were infused into the white matter of the left frontal lobe of the brain. To quantify the edema fluid cleared by the ventricular system, ventriculo-cisternal perfusion was performed with aCSF. A closed cranial window, implanted above the left parietal brain, served for studying resolution of the artificial edema fluid via the subarachnoid space. CSF-samples were collected in 30 minutes-intervals and analysed with a spectrophotometer. Clearance of edema fluid was examined under low (2-5 mm Hg), medium (9-12 mm Hg), or high (14-17 mm Hg) intracranial pressures (ICP). In the low pressure-group, both edema fluid markers were found in the ventriculo-cisternal and subarachnoid perfusate at 60 and 90 min, in the group with moderately increased ICP at 90 and 120 min, respectively. In the high ICP-group both fluorescence dyes appeared not less than 90 min in the ventricular system, while no increase at all could be found in the subarachnoid space. Our results imply that resolution of edema fluid via both the ventricular system and the subarachnoid space depends on the actual ICP level.

Animals↗

PubMed1998

Monotherapy with dextromethorphan or tirilazad--but not a combination of both--improves outcome after transient focal cerebral ischemia in rats.

Cell death after cerebral ischemia is mediated by a massive release of excitatory amino acids, generation of free radicals, and - a crucial step - calcium influx into cells. We examined the hypothesis that concurrent administration of drugs ameliorating brain damage via different mechanisms would result in a synergistic neuroprotective effect. The neuroprotective efficacy of two clinically available drugs - the N-methyl-D-aspartate and calcium-channel antagonist dextromethorphan (DM) and the antioxidant tirilazad - were studied in monotherapy and in combination in a rat model of transient focal ischemia. Male Sprague-Dawley rats were subjected to 90 min of middle-cerebral-artery occlusion by an intraluminal filament technique. The animals were randomly assigned to one of four treatments (n=10 each): (1) vehicle-treated controls, (2) DM, (3) tirilazad, (4) DM+tirilazad. Drugs or vehicles were administered 15 min before ischemia and at reperfusion. Local cerebral blood flow (LCBF) was bilaterally recorded by continuous laser Doppler flowmetry. Functional deficits were quantified by daily neurological examinations. Infarct volume was assessed planimetrically after 7 days. DM prevented post-ischemic hypoperfusion. Tirilazad did not influence LCBF. Monotherapy with DM or tirilazad improved neurological function and reduced infarct volume by 45% and 48%, respectively. Combination therapy failed to influence neurological recovery and infarct volume. Although, from pharmacological point of view, a synergistic neuroprotective effect is expected, combination of dextromethorphan and tirilazad may lead to mutual inhibition or potentiate adverse effects.

Animals↗

PubMed1998

Special aspects of severe head injury: recent developments.

Trauma in general, and head injury in particular, is the most frequent cause of mortality and morbidity in those aged up to 45 years. Outcome from severe head injury depends on the nature and severity of the primary lesion, and the manifestations of secondary brain damage of extra- and intracranial origin. The most important sequela is cerebral ischaemia resulting from intracranial hypertension caused by, for example, traumatic brain swelling or intracranial haemorrhage and/or systemic complications, of which arterial hypotension is the most significant. Because treatment so far is limited in principle to general symptomatic measures, continuing improvements in patient management is required on a comprehensive basis. In this context, major efforts are being made all over the world, not only to assess the current efficacy of, for example, logistics, organization and patient management in severe head injury, but also towards development of a consensus aimed at standardizing management and treatment procedures. With regard to the predominant influence of secondary ischaemia of the brain, recent experimental and clinical pathophysiological studies focus on the quality of cerebral blood flow, including the intriguing phenomenon of post-traumatic vasospasm. Other research objectives are concerned with the role of cytokines, leucocyte-endothelial interactions and molecular genetics in severe head injury (e.g. illuminated by the emerging role of the apolipoprotein E gene). Finally, the formation of international organizations, the American and European Brain Injury Consortium, is noteworthy. Although their primary objective is the development of guidelines for clinical trials, future objectives are conceivably more far spread and influential. It can be hoped, therefore, that the unacceptably poor outcome from severe head injury until now can be improved. Moreover, alleged management discrepancies between up-to-date trauma centres and rural hospitals may be eliminated.

Journal Article↗

PubMed1998

A critical reevaluation of the intraluminal thread model of focal cerebral ischemia: evidence of inadvertent premature reperfusion and subarachnoid hemorrhage in rats by laser-Doppler flowmetry.

BACKGROUND AND PURPOSE: The intraluminal thread model for middle cerebral artery occlusion (MCAO) has gained increasing acceptance. Numerous modifications have been reported in the literature, indicating that the technique has not been standardized. The present study was performed to evaluate and optimize the reliability of this model. METHODS: One hundred Sprague-Dawley rats were subjected to MCAO by 2 different intraluminal filaments. Cortical blood flow was continuously monitored over both hemispheres by laser-Doppler flowmetry (LDF). In part I (3-0 filament), we evaluated the incidence of adequate MCAO, subarachnoid hemorrhage (SAH), intraluminal thrombus formation, and the effects of heparinization. In part II (silicone-coated 4-0 filament), we also determined the influence of insufficient MCAO on morphological and functional outcome and the incidence of postischemic hyperthermia. RESULTS: In part I, SAH occurred in 30% and premature reperfusion in 24%. All animals with a decrease in contralateral flow had suffered SAH. Thrombus formation was not observed in any group. In part II, SAH occurred in 8% and premature reperfusion in 26%. There was no difference in outcome between rats with primary MCAO and rats with filament correction. Animals with uncorrected premature reperfusion had significantly smaller infarct volumes and fewer neurological deficits. CONCLUSIONS: SAH and insufficient MCAO may be more common in the intraluminal thread model than previously reported. Inadvertent premature reperfusion contributes to the interanimal variability associated with this model. The incidence of valid experiments increases with the use of a silicone-coated 4-0 filament. Continuous bilateral LDF is indispensable to monitor adequate MCAO and is highly sensitive to recognize SAH.

Animals↗

PubMed1997

Swelling and damage of glial cells by lactacidosis and glutamate: effect of alpha-trinositol.

The therapeutical efficacy of alpha-trinositol (D-myo-inositol-1,2,6-trisphosphate), an isomer of the intracellular messenger IP3, was analyzed on cytotoxic swelling and damage of glial cells in vitro from lactacidosis or glutamate. C6 glioma cells suspended in a physiological medium were either exposed to pH 5.0 by administration of lactic acid, or to 1 mM glutamate. Cell swelling and viability were quantified by flow cytometry. Lactacidosis of pH 5.0 led to an increase in cell volume to 139.7 +/- 1.3% within 20 min whereas alpha-trinositol was reducing the swelling response by approximately 25% (P < 0.01). In addition, at pH 5.0 the fraction of viable cells was lowered from 94.3 +/- 0.2% (control) to only 53.8 +/- 3.1% after 60 min. Alpha-trinositol was found to protect also cell viability; at 60 min of lactacidosis 70.2 +/- 1.6% of the cells still were viable (P < 0.01). The addition of glutamate (1 mM) to the cell suspension led to a steady increase in cell size, reaching 110% of control at 120 min, irrespectively of whether alpha-trinositol was added or not.

Acidosis, Lactic↗

PubMed1997

Leukocyte-endothelium interactions in global cerebral ischemia.

A closed cranial window was implanted in male Mongolian Gerbils to investigate leukocyte-endothelium interactions (LEI) at the brain surface in global cerebral ischemia (GCI) by intravital fluorescence microscopy. Four days after 15 min of bilateral common carotid artery occlusion the ischemic tissue damage was histologically analysed in selectively vulnerable areas of the brain. The frequency of Rhodamine 6G labeled leukocytes rolling along ("roller") and firmly attached ("sticker") to postcapillary endothelium was assessed before and up to 180 min after GCI. As compared to the sham operated control animals induction of LEI was found in animals with GCI, following a steady increase up to a significant level attained at 60 min (rollers) or at 120 min of reperfusion (sticker), respectively (p < 0.05). In animals with cerebral ischemia histological assessment revealed a significant decrease of viable neurons in the CA1-sector of hippocampus (neurons/mm2 +/- SEM: 1308 +/- 71 vs. 829 +/- 106), in parietal neocortex (727 +/- 17 vs. 542 +/- 49), and in striatum (547 +/- 26 vs. 352 +/- 49; p < 0.01), respectively. A significant correlation between the extent of irreversible neuronal damage and the frequency of leukocyte adherence to the endothelium could not be established. Nevertheless a direct correlation between the number of surviving neurons and of rolling leukocytes was observed, which may be suggestive of a protective potential of leukocyte rolling.

Animals↗

PubMed1997

The penumbra zone of a traumatic cortical lesion: a microdialysis study of excitatory amino acid release.

A cortical tissue necrosis from focal trauma expands to 150% of its initial volume within 24 hrs. It is currently unknown, whether this phenomenon is part of the primary traumatic lesion or if it involves secondary mechanisms such as the release of excitatory amino acids into the traumatic penumbra zone. A microdialysis probe was inserted for that purpose in an oblique angle into the cortex of Sprague-Dawley rats, approximately 2 mm below the brain surface. One day later a highly standardized cortical freezing lesion was induced at the brain cortex above the microdialysis probe. Dialysate was collected prior to, during, and after trauma in 10 min intervals. In each animal, it was confirmed histologically, that the tip of the microdialysis probe was localized in the grey matter in close vicinity to the primary lesion. Following induction of the trauma a statistically significant increase of the dialysate level of aspartate, glutamate, glycine, and serine was observed, whereas that of alanine was not altered throughout the experiment. The posttraumatic increase of the excitatory neurotransmitters aspartate and glutamate indicates that these amino acids are involved in the secondary lesion growth after trauma. Confirmation of this hypothesis would require that specific antagonization of these excitotoxic amino acids is inhibiting growth of the lesion.

Animals↗

PubMed1997

Assessment of regional cortical blood flow following traumatic lesion of the brain.

A brain tissue necrosis from trauma gradually expands during the subsequent 24 h. Among others, deterioration of perifocal blood flow could be involved in the secondary extinction of initially viable brain tissue. A highly standardized freezing lesion was made in cerebral cortex of rats for frequent measurements of regional cortical blood flow with high spatial resolution by laser Doppler scanning flowmetry. Following trauma a profound decrease in cerebral blood flow was found, not only in the lesion proper but also in the perifocal and distant brain areas, which would support a role of ischemia in the secondary lesion growth. Further studies, however, are required, particularly on whether therapeutic improvement of perifocal flow is affecting expansion of the traumatic tissue necrosis.

Animals↗

PubMed1997

Role of calcium ions in acidosis-induced glial swelling.

Tissue acidosis occurring in cerebral ischemia and traumatic brain injury is a mediator of cytotoxic brain edema. In vitro, extracellular lactacidosis induces swelling of glial cells in a dose dependent manner. pH-regulatory membrane transporters and channels have been identified which are involved in the increase of the glial cell volume. Underlying mechanisms of their activation are poorly understood, however. We have, therefore, addressed the question, whether and how Ca(2+)-ions play a role in acidosis-induced glial swelling and intracellular acidification. For that purpose C6 glioma cells were suspended and the pH in the medium was lowered from 7.4 (baseline) to 6.2 by isotonic lactic acid. Cell volume and intracellular pH (pHi) were assessed by flow cytometry. In the presence of Ca(2+)-ions the cell volume reached a maximum of 125.1% from acidosis. In experiments using a calcium-free suspension medium, cell swelling from acidosis was inhibited by 74%. Additional buffering of intracellular calcium (Ca2+i) had no further inhibitory effect on acidosis-induced cell swelling, while buffering of Ca2+i by BAPTA-AM alone did not affect the glial volume increase secondary to administration of lactic acid. pHi which was decreasing from acidosis was not affected by the experimental modifications of the Ca(2+)-concentration in the medium or cytosol. The present data indicate that lactacidosis-induced glial swelling depends on the presence of extracellular Ca(2+)-ions, while release of Ca(2+)-ions from intracellular stores does not seem to be involved.

Acidosis↗

PubMed1997

Neuroprotective properties of a novel antioxidant (U-101033E) with improved blood-brain barrier permeability in focal cerebral ischemia.

Many efforts have been undertaken to develop antioxidants against free radical induced brain damage, 21-aminosteroids, although accumulating in the cell membrane, thus protecting vascular endothelium from peroxidative damage hardly penetrate the blood-brain barrier. A novel group of antioxidants, the pyrrolopyrimidines, has a markedly improved ability to enter the brain parenchyma. In our current study the neuroprotective potential of the 21-aminosteroid U-74389G was compared with that of the pyrrolopyrimidine U-101033E in a rat model of reversible focal cerebral ischemia. Sprague-Dawley rats were subjected to unilateral occlusion of the middle cerebral artery with assignment to one of three treatment arms (n = 10 each), receiving either vehicle, U-74389G, or U-101033E. Regional CBF was recorded bilaterally by laser Doppler flowmetry. In addition, neurological examination was performed daily, with assessment of infarct volume at day seven. U-101033E reduced the infarct volume significantly by 51%, whereas U-74389G afforded non-significant attenuation only. U-101033E was found to improve neurological recovery promptly; animals with U-74389G began to recover only at the end of the experimental observation period. Differences in the regional CBF were not found in the contralateral hemispheres for either treatment group. We conclude that antioxidative compounds which cross the blood-brain barrier are more effective in focal cerebral ischemia than agents which predominantly act on the endothelium of cerebral microvessels.

Animals↗

PubMed1997

Effect of alpha-trinositol on swelling and damage of glial cells by lactacidosis and glutamate.

The therapeutic efficacy of alpha-trinositol (D-myo-inositol-1,2,6-trisphosphate), an isomer of the intracellular messenger IP3, was analyzed for cytotoxic swelling and damage of glial cells in vitro from lactacidosis or glutamate. Lactacidosis and the interstitial accumulation of glutamate are prominent sequelae in ischemic or traumatic brain tissue. C6 glioma cells harvested from culture and suspended in a physiological medium were either exposed to pH 5.0 by administration of lactic acid, or to 1 mM glutamate at normal pH. Cell swelling and viability were quantified by blood flow cytometry. Addition of alpha-trinositol (3 mM) under control conditions at pH 7.4 resulted in transient cell shrinking to 96.5 +/- 1.3% of control within 3 min (p < 0.05). Lactacidosis of pH 5.0 led to an increase in cell volume to 139.7 +/- 1.3% within 20 min, whereas alpha-trinositol reduced the swelling response by approximately 25% (p < 0.01). In addition, cell viability was severely affected at pH 5.0 amounting to only 53.8 +/- 3.1% after 60 min. alpha-Trinositol was found to markedly improve cell viability; at 60 min 70.2 +/- 1.6% of the cells were still viable (p < 0.01). Addition of glutamate (1 mM) led to a steady increase in cell size, reaching 110% of control after 120 min, irrespective of wether alpha-trinositol was present or not. The attenuation of cell swelling may be attributed to an interference with pH-regulatory mechanisms, such as the Na+/H(+)-antiporter, while protection of cell viability might be caused be effects of alpha-trinositol on Ca(2+)-overload. On the other hand, the increase in cell volume by glutamate associated with its intracellular uptake was not influenced by alpha-trinositol.

Acidosis, Lactic↗

PubMed1997

Role of protein kinase C in acidosis induced glial swelling--current understanding.

A major factor in secondary brain injury following cerebral trauma is accumulation of lactic acid resulting in glial swelling. Further, evidence obtained in this context demonstrates activation of protein kinase C (PKC) under these circumstances. Glial swelling from acidosis is attributable to activation of the Na+/H(+)-exchanger, mediating influx of Na(+)-ions in exchange for the extrusion of H+ ions. The antiporter is activated following phosphorylation by PKC. The current study was made to elucidate the role of PKC activation in acidosis-induced glial swelling. For that purpose, suspended C6 glioma cells were used to examine changes of the cell volume and intracellular pH (pHi). Acidosis was induced by administration of isotonic lactic acid. Stimulation of PKC by the phorbol-ester PMA was significantly enhancing glial swelling from severe acidosis (pH 6.2), whereas the decrease of pHi was somewhat attenuated. On the other side, inhibition of PKC by staurosporine did not affect cell swelling nor the decrease of pHi from acidosis. The results indicate that activation of PKC in cerebral trauma or ischemia may enhance glial swelling from lactacidosis.

Acidosis, Lactic↗

PubMed1997

Effect of mild and moderate hypothermia on the acidosis-induced swelling of glial cells.

The effect of mild (32 degrees C) and moderate (27 degrees C) hypothermia was analyzed on the cell volume and intracellular pH (pHi) of C6 glioma cells at normal pH and during lactacidosis at pH 6.2 in vitro. The cells were suspended in an incubation chamber under continuous control of pH, PO2 and temperature. Cell swelling was quantified by an advanced Coulter-system. pHi was measured by flow cytometry using the fluorescent dye bis-carboxyethyl carboxyfluorescein (BCECF). Following a control period at 37 degrees C, the ambient temperature was decreased to 32 degrees C for 30 min, and subsequently to 27 degrees C for another 30 min. Hypothermia alone led to an immediate and significant cell volume increase of 107.3 +/- 0.4% (mean +/- SEM) of control after 30 min at 32 degrees C, and further swelling to 110.5 +/- 0.9% after 30 min at 27 degrees C. Yet, hypothermia (27 degrees C) afforded partial protection against the acidosis-induced cell swelling at pH 6.2, which was reaching to 120.4 +/- 0.9% in the normothermic control group after 60 min, while only to 111.3 +/- 0.9% at 27 degrees C. Hypothermia, however, was associated with a more pronounced decrease of the pHi during acidosis (6.3 +/- 0.04) as compared to that of the normothermic control falling then to 6.5 +/- 0.03. The results demonstrate that mild and moderate hypothermia induce glial cell swelling, but simultaneously inhibit cell swelling from acidosis. The protection against cell swelling, however, has its price as indicated by the enhancement of the intracellular acidification.

Acidosis, Lactic↗