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PubMed2001

Ocular pharmacokinetics in rabbits using a novel dual probe microdialysis technique.

Ocular infections involve delicate internal structures of the eye that often require treatment with antimicrobial agents. A major constraint to the study of ocular drug absorption from systemic administration is the inaccessibility of the vitreous for continuous serial sampling. A novel dual probe microdialysis technique has been employed in our laboratory, which will enable the delineation of complete ocular pharmacokinetics of a drug. New Zealand albino rabbits weighing 2--2.5 kg were used. The animals were kept under anesthesia throughout the experiment. A concentric probe was implanted in the vitreous chamber about 3 mm below the corneal scleral limbus. Simultaneously a linear probe was implanted in the anterior chamber across the cornea. Intraocular pressure (IOP) was measured using Schiotz tonometer. The total protein concentrations in the aqueous and vitreous humors were determined using the Bio-Rad protein assay method. The aqueous and vitreous elimination kinetics of fluorescein were studied after intravitreal and systemic administrations over a period of 10 hr. Microdialysis technique was also compared to the conventional direct sampling technique by determining the intravitreal kinetics of fluorescein. Results suggest that IOP reverted to normal within 2 hr after the implantation of the probes. The increase in the vitreal total protein concentration was not significantly different from the baseline. The increase in the aqueous total protein concentration was less than five times the basal concentration throughout the experiment. The blood-aqueous and blood-retinal barrier integrity was delineated by determining the permeability index for fluorescein and were found to be 9.48 +/- 4.25% and 1.99 +/- 0.66% for the anterior and vitreous chamber, respectively. The rate constant of penetration of fluorescein into the anterior chamber was found to be 8.48 +/- 1.33 x 10(-2) min(-1), which was significantly higher than into the vitreous i.e. 4.34 +/- 2.82 x 10(-2) min(-1). The terminal elimination rate constant of fluorescein from the anterior chamber (1.48 +/- 0.79 x 10(-2) min(-1)) was found to be similar to that of the plasma terminal elimination rate constant (1.57 +/- 0.25 x 10(-2) min(-1)), but significantly higher than from the vitreous (3.0 +/- 0.7 x 10(-3) min(-1)). The terminal vitreal elimination rate constant of fluorescein after intravitreal administration was found to be similar by both microdialysis (3.98 +/- 0.6 x 10(-3) min(-1)) and direct sampling (4.38 +/- 1.4 x 10(-3) min(-1)) techniques. In case of direct sampling technique the area under the vitreous concentration-time curve was higher compared to that obtained by the microdialysis technique. There was no breakdown of the blood ocular barriers as shown by a very small change in the intraocular fluid protein concentrations. This was also confirmed by the fluorescein kinetics, which were in accordance with the previous studies. IOP data suggests that the intraocular fluid dynamics were not affected and the animals stabilized within 2 hr after the implantation of the probes. Fluorescein data suggests that the vitreous compartment is surrounded by a tighter barrier compared to the anterior chamber. This technique appears to be more sensitive, reproducible and requires only one animal for the determination of entire ocular pharmacokinetic profile.

Animals↗
PubMed2005

Glucose metabolism in traumatic brain injury: a combined microdialysis and [18F]-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) study.

Following traumatic brain injury, as a consequence of ionic disturbances and neurochemical cascades, glucose metabolism is affected. [18F]-2-Fluoro-2-deoxy-D-glucose (FDG) Positron Emission Tomography (FDG-PET) provides a measure of global and regional cerebral metabolic rate of glucose (rCMRglc), but only during the time of the scan. Microdialysis monitors energy metabolites over extended time periods, but only in a small focal volume of the brain. Our objective in this study is to assess the association of parameters derived from these techniques when applied to patients with traumatic brain injury. Eleven sedated, ventilated patients receiving intracranial pressure monitoring and managed using Addenbrooke's Neurosciences Critical Care Unit protocols were monitored. Dialysate values for glucose, lactate, pyruvate, and glutamate, and the lactate to glucose (L/G), lactate to pyruvate (L/P) and pyruvate to glucose (P/G) ratios were determined and correlated with rCMRglc. FDG-PET scans were performed within 24 hours (five patients), or between 1 and 4 days (two patients) or after 4 days (six patients). Two patients were rescanned 4 and 7 days after their initial scan. A 20 mm region of interest (ROI) was defined on co-registered CT scan on two contiguous slices around the microdialysis catheter. Mean (+/-sd) for rCMRglc was 19.1 +/- 5.5 micromol/100 g/min, and the corresponding microdialysis values were: glucose 1.4 +/- 1.4 mmol/ L; lactate 5.3 +/- 3.6 mmol/L; pyruvate 164.1 +/- 142.3 micromol/L; glutamate 15.0 +/- 14.7 micromol/L; L/G 11.0 +/- 16.0; L/P 27.3 +/- 7.9 and P/G 381 +/- 660. There were significant relations between rCMRglc and dialysate lactate (r = 0.58, P = 0.04); pyruvate (r = 0.57, P = 0.04), L/G (r = 0.55, P = 0.05), and the P/G (r = 0.56, P = 0.05) but not between rCMRglc and dialysate glucose, L/P or glutamate in this data set. The results suggest that increases in glucose utilization as assessed by FDG-PET in these patients albeit in mainly healthy tissue are associated with increases in dialysate lactate, pyruvate, L/G and the P/G ratio perhaps indicating a general rise in metabolism rather than a shift towards non-oxidative metabolism. Further observations are required with regions of interest (microdialysis catheters positioned) adjacent to mass lesions notably contusions.

Adolescent↗
PubMed1996

A novel microdialysis probe designed for clinical use: potential analytical and therapeutic applications.

Significant obstacles to the use of microdialysis in the clinic for diagnostic or therapeutic purposes include the production of dedicated entry port through the skull and the formation of a tract by the insertion of a probe into the parenchyma. We have developed a microdialysis probe that is minimally invasive and can be combined with an intracranial pressure probe, recording electrode, or other intracranial probe, that is minimally invasive. Yet the surface area of this probe is very high, permitting high recovery efficiencies even at relatively high flow rates. This probe design makes possible minimally invasive measurement of the peroxidation product, uric acid, and excitatory amino acids, two analytes that increase in experimental traumatic brain injury in animals. Moreover, its large surface area makes therapeutic applications of microdialysis probes in the brain potentially feasible. A pilot evaluation of the ability of microdialysis to have therapeutic benefit in limiting experimental excitotoxin lesions induced in rat striatum by N-methyl-D-aspartate (NMDA) is reported.

Animals↗
PubMed1996

Intracerebral microdialysis markedly inhibits the propagation of cortical spreading depression.

It is accepted that the ionic composition of the medium perfused through a microdialysis probe should match that of the extracellular fluid (ECF) under physiological conditions. In contrast, the possibility that control artificial cerebrospinal fluid may influence the experimental or pathological conditions under study, by buffering changes in the ECF composition, has been neglected. Spreading depression (SD) is a propagating transient suppression of electrical activity due to cellular depolarization which may contribute to neuronal damage in focal ischaemia, and underlie the migraine aura Here we report that microdialysis markedly inhibits SD propagation, by buffering the sudden increase in extracellular K+ associated with this event. This effect is independent of the microdialysis flow rate and does not result from tissue injury following probe implantation. This finding clearly illustrates that microdialysis can influence the pathological conditions under investigation.

Animals↗
PubMed1994

Continuous monitoring of lactate during exercise in humans using subcutaneous and transcutaneous microdialysis.

We have evaluated the possibility of monitoring the plasma lactate concentration in human volunteers during cycle ergometer exercise using subcutaneous and transcutaneous microdialysis. In transcutaneous microdialysis, the relative increase in dialysate lactate concentration exceeded that of plasma lactate concentration by a factor of 6 during exercise due to exercise-induced lactate secretion in sweat. During exercise the subcutaneous microdialysis dialysate lactate concentration underestimated the plasma lactate concentration possibly due to diffusion limitation or adipose tissue lactate production. While it was demonstrated that microdialysis can be used for on-line lactate monitoring, neither subcutaneous nor transcutaneous dialysate lactate concentration were linearly related to the plasma lactate concentration during exercise, and it was found therefore that it was not possible to monitor directly plasma lactate concentration during exercise.

Adult↗
PubMed2001

Human adipose tissue glucose uptake determined using [(18)F]-fluoro-deoxy-glucose ([(18)F]FDG) and PET in combination with microdialysis.

AIMS/HYPOTHESIS: To determine the lumped constant (LC), which accounts for the differences in the transport and phosphorylation between [(18)F]-2-fluoro-2-deoxy-d-glucose ([(18)F]FDG) and glucose, for [(18)F]FDG in human adipose tissue. METHODS: [(18)F]FDG-PET was combined with microdialysis. Seven non-obese (29 +/- 2 years of age, BMI 24 +/- 1 kg/m2) and seven obese (age 32 +/- 2 years of age, BMI 31 +/- 1 kg/m2) men were studied during euglycaemic hyperinsulinaemia (1 mU/kg. min-1 for 130 min). Abdominal adipose tissue [(18)F]FDG uptake (rGUFDG) and femoral muscle glucose uptake were measured using [(18)F]FDG-PET. Adipose tissue perfusion was measured using [15O]-labelled water and PET, and interstitial glucose concentration using microdialysis. Glucose uptake (by microdialysis, rGUMD) was calculated by multiplying glucose extraction by regional blood flow. The LC was determined as the ratio of rGUFDG to rGUMD. RESULTS: Rates of adipose tissue glucose uptake (rGUMD) were 36 % higher in the non-obese than in the obese patients (11.8 +/- 1.7 vs 7.6 +/- 0.8 micromol/kg. min-1, p < 0.05, respectively) and a correlation between rGUMD and rGUFDG was found (r = 0.82, p < 0.01). The LC averaged 1.14 +/- 0.11, being similar in the obese and the non-obese subjects (1.01 +/- 0.15 vs 1.26 +/- 0.15, respectively, NS). Muscle glucose uptake was fourfold to fivefold higher than adipose tissue glucose uptake in both groups. CONCLUSION/INTERPRETATION: [(18)F]FDG-PET seems a feasible tool to investigate adipose tissue glucose metabolism in human beings. Direct measurements with [(18)F]FDG-PET and microdialysis suggest a LC value of 1.14 for [(18)F]FDG in human adipose tissue during insulin stimulation and the LC does not appear to be altered in insulin resistance. Furthermore, the obese patients show insulin resistance in both adipose tissue and skeletal muscle.

Adipose Tissue↗
PubMed1999

Effect of novel environmental stimuli on rat behaviour and central noradrenaline function measured by in vivo microdialysis.

RATIONALE: Although physically aversive stimuli induce functional changes in central noradrenergic neurones, little is known about the noradrenergic response to environmentally aversive stimuli. OBJECTIVES: The first aim was to characterise environmental features that are perceived as stressful by rats. The second was to investigate whether changes in the concentration of extracellular noradrenaline are induced by these environmental features. METHODS: A light/dark shuttle-box was used to test rats' behavioural response to a range of stimuli (novelty, bright light, and the presence of an unfamiliar rat), either before or after microdialysis probe implantation. Changes in the concentration of extracellular noradrenaline in the frontal cortex and hypothalamus in vivo were then evaluated on exposure to these same test conditions. RESULTS: Naive rats spent less time in a brightly-lit test arena than a dark one. However, the behavioural response to the light arena was attenuated by the presence of an unfamiliar rat. Probe implantation intensified the response to the light arena but did not affect behaviour in the dark arena. In the microdialysis studies, there was no change in the concentration of extracellular noradrenaline on transfer of rats to the dark arena but there was an increase in both the frontal cortex (+45%) and hypothalamus (+75%) on exposure to the light arena. A similar increase was induced in both brain regions when the light arena contained an unfamiliar rat. CONCLUSIONS: Implantation of a microdialysis probe modifies the behavioural responses to certain environmental stimuli. Regardless of this, the extent to which rats perceive a novel environment as aversive is not the only determinant of the noradrenergic response to such stimuli. However, differences in stimulus controllability in the microdialysis and the behavioural experiments could influence the apparent intensity of the stress.

Animals↗
PubMed2003

Perioperative penetration of metronidazole into muscle tissue: a microdialysis study.

OBJECTIVE: To evaluate the concentration of metronidazole in muscle tissue using microdialysis and to compare it with plasma concentration and in vitro-defined MIC(90) (minimal inhibiting concentration) for the most frequent anaerobic bacteria isolated in our hospital. MATERIALS AND METHODS: Six female patients scheduled for elective gynaecological surgery were included. Exclusion criteria were active inflammatory process and being overweight (BMI more than 30). Microdialysis catheters (CMA 60 catheters with 20 kDa cut-off membrane) were placed into the m. vastus lateralis. The microdialysis perfusion rate was 2 microl/min. To assess in vivo recovery of the drug, retrodialysis with a 5-mg/l solution of metronidazole was performed. Microdialysis and blood samples were collected simultaneously 10 h after metronidazole administration. MIC(90) data were obtained from the database of the microbiology laboratory of the local hospital. RESULTS: Data from five patients were included in analysis. The metronidazole concentration in blood achieved a value of 16.5+/-4.6 mg/l at 30 min (first available data), while in muscle a maximum level of 7.8+/-1.5 mg/l was achieved at 114 min. The mean MIC(90) for the Bacteroides fragilis group was 0.25+/-0.26 mg/l. Data from mean plasma concentrations were fitted into the two-compartmental model and time over MIC(90) and time over four times MIC(90) were calculated, which were 52.1+/-13.5 h and 33.2+/-8.7 h, respectively. The C(max)/MIC(90) ratio was 65.8+/-18.5 for plasma and 31.1+/-6.2 for muscle. CONCLUSION: The present data demonstrate that metronidazole penetrates well into muscle tissue. Muscle tissue concentrations reach values far greater than MIC(90) for the Bacteroides fragilis group and persist at such high levels for at least 10 h.

Adult↗
PubMed1993

Long-term continuous glucose monitoring with microdialysis in ambulatory insulin-dependent diabetic patients.

The glucose concentration in the extracellular space of subcutaneous adipose tissue closely mirrors the blood glucose concentration. With a microdialysis technique, we undertook continuous ambulatory monitoring of adipose tissue glucose in 17 insulin-dependent diabetic patients with labile glycaemic control. The aims of the study were to investigate performance of the microdialysis device and to evaluate whether consecutive 24 h glucose profiles could be used to adjust insulin therapy. A microdialysis probe was implanted subcutaneously, perfused by a portable microinfusion pump, and dialysate fractions were collected every 1 or 2 h for 75 h. The mean (SE) tissue dialysate glucose concentration was 93 (3)% of the concentration in venous plasma, and variations in adipose tissue glucose closely paralleled changes in plasma glucose. Mean 24 h tissue glucose concentration correlated significantly with glycosylated haemoglobin (HbA1c; r = 0.62, p < 0.01). Most patients had a reproducible daily pattern of glucose swings, and in more than half the patients consecutive ambulatory glucose profiles were almost superimposed. When patients' insulin therapy was adjusted on the basis of ambulatory glucose monitoring, HbA1c decreased by almost 2% (p < 0.01), and this decrease lasted for at least 9 months. Microdialysis of adipose tissue can be used for continuous long-term monitoring of glucose concentrations in diabetic patients during ordinary daily life. Daily glucose profiles are often reproducible and the recordings may thus be used for individual tailoring of insulin therapy to improve glycaemic control.

Adipose Tissue↗
PubMed1994

Study of 5-HT release with a chronically implanted microdialysis probe in the ventral horn of the spinal cord of unrestrained rats during exercise on a treadmill.

The ventral horn of the spinal cord is profusely innervated by serotonin (5-hydroxytryptamine, 5-HT) which presumably modulates locomotor activity through motoneurons. However, direct evidence of correlation between 5-HT release and activation of motoneurons is still lacking. In order to appreciate the functional characteristics of this innervation, we have used microdialysis to monitor the release of 5-HT in the spinal cord of rats spontaneously running on a treadmill. For this purpose, we developed an original surgical procedure adapted for the chronic implantation of a microdialysis probe in the lumbar spinal cord. The probe was kept in place for 40 days, and microdialysis experiments were carried out at days 8, 16, 20 and 32. 5-HT was detected with HPLC coupled to electrochemistry. This technique demonstrated that release of 5-HT is not increased during exercise. However, a significant decrease was measured during postexercise rest. 5-HT could still be detected 32 days after probe implantation. Detailed histological and immunocytochemical analysis based on glial fibrillary acidic protein and 5-HT immunocytochemistry showed minimal gliosis and the presence of serotonergic varicose fibers, respectively, at the probe contact. It thus appears that microdialysis can be performed through a probe implanted chronically in the spinal cord of unrestrained rat during an endurance running exercise.

Animals↗
PubMed1995

In vivo microdialysis and gas chromatography/mass spectrometry for studies on release of N-acetylaspartlyglutamate and N-acetylaspartate in rat brain hypothalamus.

Microdialysis and gas chromatography/mass spectrometry was used for the measurement of extracellular N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) in rat hypothalamus. The sensitivity of the method for each of these compounds was approximately 5 pmol/30 microliters of dialysate. Baseline NAA concentrations in dialysate were estimated to be approximately 25 pmol/36 microliters, while that for NAAG was at or below the detection limit of 5 pmol/ 36 microliters. In vivo and in vitro calibrations of microdialysis probes showed that the recovery for NAA was approximately 10 percent. For NAAG, the in vitro recovery was 6.3%, and in vivo recovery, 11%. Depolarization stimulation using 100 mM KCl in the microdialysis perfusate was employed to measure extracellular NAA and NAAG concentrations. Extracellular NAA was elevated to approximately 70 pmol/36 microliters dialysate following depolarization. No significant elevation of NAAG was observed. By infusing known amounts of stable isotopically labeled NAAG-d3 via the microdialysis probe and measuring the isotopically labeled catabolic product, NAA-d3, in collected microdialysate, we were able to confirm the existence of one or more hydrolytic enzymes active towards NAAG in the hypothalamus. This finding suggest the possible involvement of active metabolic processes in the relationship between NAAG and NAA releases.

Animals↗
PubMed1996

Evaluation of the function of microdialysis probes permanently implanted into the rat CNS and coupled to an on-line HPLC system of analysis.

The aim of the microdialysis technique is to reflect as closely as possible the status and fluctuations of substances contained in the extracellular space. Most often, microdialysis is performed with repetitively implanted probes. We have recently devised an experimental set-up which allows microdialysis to be performed in the spinal cord of unrestrained rats through chronically permanently implanted probes. In the present study, we have compared the in vitro recovery of a non-biogenic amine (DHBA) and of 5-HT, and the in vivo recovery of the former. Thus, we could extrapolate the in vivo recovery of endogenous 5-HT released. Moreover, we have found that the recovery does not vary irrespective of whether the animal is at rest or performing sustained physical exercise, and that it also remains stable with time, from 8 to 36 days after permanent implantation of the probe. We conclude that this simple method can be applied to standard experiments of microdialysis, and thus allow one to measure the actual rate of recovery for a given probe. Moreover, it permits control of the stability of dialysis parameters with time for long-term permanently implanted probes.

Animals↗
PubMed1994

Neurochemical effects of prolonged treatment with remoxipride as assessed by intracerebral microdialysis in freely moving rats.

1. At three microdialysis sessions, dialysates were collected from the striatum of the same rats. 2. Microdialysis session 1. A single s.c. injection of remoxipride (40 mumol/kg), resulted in increased dialysate concentrations of dopamine, DOPAC and HVA. 3. Microdialysis session 2. Continuous administration of remoxipride (8.6 mumol/rat/day) for 14 days, using mini-osmotic pumps, produced maintained elevated levels of dopamine, DOPAC and HVA. 4. Microdialysis session 3. A challenge dose of remoxipride (40 mumol/kg s.c.), given to the rats after a 48-hour wash-out period following the continuous remoxipride treatment, increased the dialysate concentrations of dopamine, DOPAC and HVA to similar extent as at dialysis session 1. 5. It is concluded that after long-term treatment of remoxipride, an adaptation of the basal state of the DA system appears to take place, implying a lowering of basal DA release and DA metabolism. However, the capacity to respond with increased DA release and DA metabolism to renewed remoxipride treatment is retained, indicating little, if any, tolerance.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Effect of tetrodotoxin and potassium infusion on microdialysis extraction fraction and extracellular dopamine in the nucleus accumbens.

The effects of tetrodotoxin (TTX) and K+ perfusion on extracellular DA concentration (DAext) and extraction fraction (also known as relative recovery or Ed) were studied using a method for quantitative microdialysis under transient conditions. TTX administered through the microdialysis probe decreased DAext with no effect on Ed. Perfusion with high K+ increased DAext, with no initial effect on Ed. However, a decrease in Ed was observed under prolonged depolarization. These data provide further evidence that Ed may change over the course of drug administration. This method of quantitative microdialysis is a reliable means for measuring changes in DAext independently of possible changes in microdialysis probe efficiency.

Animals↗
PubMed1995

Automated analytical systems for drug development studies. Part IV. A microdialysis system to study the partitioning of lomefloxacin across an erythrocyte membrane in vitro.

An automated system utilizing microdialysis sampling, intermittent dosing, and liquid chromatographic analysis was assembled in order to study the partitioning of lomefloxacin, a fluoroquinolone antimicrobial, into human erythrocytes in vitro. The apparent erythrocyte:buffer partition coefficient was found to be approximately 2.0 with this system and by a manual method. The value was concentration-dependent; lower partition coefficients were observed at lomefloxacin concentrations less than 1 microgram ml-1. At all concentrations, values obtained by microdialysis were statistically indistinguishable from those obtained by a conventional manual method. The results indicate that erythrocyte partition coefficients can be measured successfully with the microdialysis system. Furthermore, microdialysis sampling eliminates the tedious methodology associated with traditional erythrocyte partitioning studies, including sample clean-up. Due to automated intermittent dosing and on-line LC analysis, the system operates unattended.

Adult↗
PubMed1995

Microdialysis measurement of intracerebral somatostatin in the goat.

A microdialysis sampling technique for the intracerebral measurement of somatostatin (SS) in extracellular fluid was examined in the goat. The microdialysis probe (70-mm shaft, 0.5 mm outer diameter) contained at its tip a 4-mm length of copolymer dialysis membrane (20 kDa cut-off). Artificial cerebrospinal fluid (artificial CSF) was pumped through the probe tip at a rate of 4 microliters/min with a batter-driven syringe pump, and effluent fractions of dialysate (120 microliters) were collected every 30 min. An in vitro recovery test showed that changes in the SS concentration in dialysate were highly correlated (r = 0.95, P < 0.01) with those in the external medium, and the relative recovery averaged 2.0%. As a validation for in vivo microdialysis, trails were conducted with conscious behaving goats wherein the inflow dialysate was changed transiently from artificial CSF with low potassium (2.5 mM) to a solution of 300 mM KCl. Potassium-induced depolarization around the probe tip located in the preoptic area and in the hypothalamus induced an increase in SS concentrations in dialysate at each location. In the most remarkable response, the concentrations of SS were increased 6-fold and 11-fold in the first and second 30-min fractions, respectively, compared with prepotassium concentrations. These results suggest that intracerebral SS levels in extracellular fluid could be estimated from conscious behaving goats by the use of our intracerebral microdialysis system.

Animals↗
PubMed1993

A method for estimation of extracellular concentration of compounds by microdialysis using urea as an endogenous recovery marker in vitro validation.

A new, practical method called microdialysis has been developed for the estimation of free, unbound drug concentrations in the interstitial fluid. This method is based on the use of urea as an endogenous recovery marker. Urea freely distributes throughout the body water compartment, and its plasma concentration can be used as an accurate measure of its interstitial levels. Microdialysis exploits the relationship between the relative recoveries of urea and the recoveries of an analyte that are established during calibration. The calibration is carried out using different probes, varying perfusion rates, membrane surface areas, temperatures, and tissue models. After obtaining a broad range of recoveries, an empirical mathematical model of the relationship between the recovery of the respective analyte and that of urea is formed. During in vivo experiments, a microdialysis probe is placed into a tissue or fluid of interest, and the urea recovery is monitored by comparing the corresponding dialysate and plasma urea levels. From the calculated urea recoveries, correlation equation, and analyte dialysate concentrations, the extracellular concentration of the unbound analyte in the tissue or fluid can be estimated at any given time point. The purpose of this study is to describe the method of microdialysis and demonstrate its applicability in vitro using two model compounds, theophylline and 3'-azido-3'-deoxythymidine (AZT), in the rat plasma.

Animals↗
PubMed2006

[Microdialysis and brain injury: importance of animal study].

Brain microdialysis allows the exploration of brain extracellular medium. This review discusses the main contribution of brain microdialysis for the knowledge of the pathophysiology of brain ischemia and trauma. We describe fundamental principle of microdialysis, limits, and validated metabolic parameters as the lactate/pyruvate ratio or glycerol. The interest to use microdialysis for testing metabolic hypothesis and potential scientific research ways will also be discussed.

Animals↗