Aminadav Mendelowitsch

Extracellular antioxidants and amino acids in the cortex of the rat: monitoring by microdialysis of early ischemic changes.

Extracellular concentrations of ascorbic acid, glutathione, cysteine, uric acid, tyrosine, and tryptophan were monitored using intracerebral microdialysis in the left frontoparietal cortex of spontaneous hypertensive rats before, and for 3 h after, either focal ischemia [left middle cerebral artery occlusion (MCAO)] or sham operation. The size of the ischemic area and the position of the microdialysis probe were checked using the enzyme histotopochemical acid phosphatase reaction. The probe was always located in the cortex inside the stained area. Ascorbic acid levels rose immediately after MCAO and remained at about 12-fold for 3 h. There was a transient release of glutathione during 1–1.5 h. Uric acid concentrations were also increased but the differences did not reach significance. The levels of the amino acids tyrosine and tryptophan increased steadily after MCAO. The increases in cysteine were variable but significant. In some experiments, the pH of the dialysate was measured online. The parameters ascorbic acid, glutathione, cysteine, and pH are suitable for the early detection of cortical ischemic events by microdialysis.

Experimental and clinical monitoring of glucose by microdialysis

The aim of this investigation was to assess the use of cerebral extracellular glucose as a parameter for microdialytic monitoring in neurosurgical critical care patients. Samples were collected from four patients with severe head injury and one with subarachnoid haemorrhage for periods of 4.5-67 h. Glucose and lactate were analysed in the dialysates. The ratios of glucose to lactate were calculated to partially allow for changes in microdialytic conditions over time. On-line pH was measured for up to 3 days in three patients. In experiments with spontaneous hypertensive rats we found that extracellular glucose became unmeasurable in the ischemic zone after middle cerebral artery occlusion. Similarly, in 3 patients glucose became undetectable for several hours, and glucose/lactate tended to decrease during measurement. This was accompanied by high ICP in one patient, and by a hypoxic episode in another. In the two other patients glucose/lactate ratios showed a rising trend. Findings indicate that glucose, and the glucose/lactate ratio show some correlations with clinical course and are promising parameters for cerebral monitoring and therapeutic decision making.

Microdialytic monitoring during cerebrovascular surgery

Using microdialysis, levels of metabolites in the extracellular fluid of the cerebral cortex were monitored during neurovascular surgery (9 aneurysm and 5 extra-intracranial bypass operations). Our aim was to use microdialysis to detect any local ischemia which might be caused by brain retraction or temporary clipping. Parameters were therefore quantified whose levels in the dialysate are known to be influenced by ischemia (on-line pH, ascorbic acid, uric acid, glutathione, cysteine, glucose, lactate, glucose:lactate ratio). In the aneurysm series, on-line pH fell after introduction of the retractor, and in the majority of cases the other parameters also showed changes in accordance with ischemic conditions in the region of the probe. These changes disappeared at the end of retraction, or sometimes even before. During the bypass operations, there were no marked changes in on-line pH or in any of the measured parameters. However, in some of these patients values for the glucose:lactate ratio, ascorbic acid and uric acid lay outside the suggested basal levels for minimally disturbed cortex, indicating possible changes in metabolism caused by inadequate perfusion (carotid artery occlusion). We conclude that microdialysis is a sensitive method of detecting intraoperative changes in cerebral metabolism.

Extracellular levels of glucose and lactate measured by quantitative microdialysis in the human brain

Abstract The aim of this study was to use quantitative microdialysis to estimate the true extracellular concentrations of glucose and lactate in minimally disturbed human brain. These values are important as criteria for microdialytical monitoring in critical care patients and for determining therapy. Microdialysis procedures were carried out during tumor operations, the probe being inserted distant from the site of manipulation in minimally disturbed tissue. Two methods were used: 1. The zero net flux method of Lönnroth. 2. The low flow method (10 mm membrane length, flow rate 0.3 µl min-1, high in vivo recovery). Both methods gave similar values of about 2000 µM for lactate and slightly less for glucose (1700 µM). Glucose levels correspond with those measured by other methods in humans, allowing for the fact that our patients were anesthetised. Extracellular glucose levels were positively correlated with blood glucose values measured before the operation, and with extracellular lactate. Results confirm that extracellular glucose is zero when blood glucose is about 2 mM. [Neurol Res 2001; 23: 531-536]

Acute treatment with red wine polyphenols protects from ischemia-induced excitotoxicity, energy failure and oxidative stress in rats

Red wine polyphenolic compounds (RWPC) possess numerous neuroprotective activities that may be beneficial for treating cerebral ischemia. To investigate the in vivo effects of an acute treatment with RWPC during stroke, male Wistar rats were subjected to transient ischemia for 90 min and immediately treated with RWPC. The extracellular concentrations of excitatory amino acids, free radical scavengers and energy metabolites during occlusion and reperfusion were monitored using microdialysis. The brain lesions were measured 24 h after reperfusion using immunohistological staining. We found that acute treatment with RWPC significantly reduced the burst of amino acids glutamate, aspartate and taurine in response to ischemia and increased the levels of free radical scavengers ascorbic and uric acids during occlusion or at early reperfusion, respectively. The concentration of glucose was improved during occlusion whereas the level of lactate strongly decreased during reperfusion in RWPC treated animals, suggesting an increased use of this substrate by surviving neurons. RWPC also significantly improved blood flow during reperfusion and brain tissue preservation as observed 24 h after MCAO in treated animals. These findings strongly suggest that RWPC are agents able to fight against the excitotoxic, oxidative pathways and metabolic dysfunction induced by cerebral ischemia.

EC-IC bypass improves chronic ischemia in a patient with moyamoya disease secondary to sickle cell disease:An in vivo microdialysis study

Patients with sickle cell disease may develop intracranial vascular disease, with the occlusion or obstruction of the large or small arteries, which may lead to the secondary development of moyamoya disease. In this report, we describe the neurochemical changes in the brain before, during, and after an extracranial-intracranial bypass procedure on a patient with sickle cell disease and a moyamoya disease like pattern on angiography. We used the in vivo microdialysis technique to measure the on-line pH, lactate and amino acid concentrations in the extracellular fluid. There were relatively high resting glutamate levels and a lower-than-normal pH in the extracellular fluid prior to the bypass, associated with chronic ischemia. During the bypass there was a short-lived increase in the glutamate levels. After revascularization, there was a rapid decrease in the glutamate levels and an increase in the pH value. The patients preoperative neurological deficit improved post-operatively, corresponding to the biochemical changes towards normal values. These changes after revascularization suggest that chronic biochemical abnormalities due to brain ischemia may improve after cerebral revascularization.

EFFECTS OF ISOFLURANE ON GLUTAMATE AND TAURINE RELEASES, BRAIN SWELLING AND INJURY DURING TRANSIENT ISCHEMIA AND REPERFUSION

The volatile anesthetic agent isoflurane was thought to provide neuroprotection against ischemic damage; however, this effect remains controversial. Using the middle cerebral artery occlusion model and intracerebral microdialysis, the authors monitored the variations of glutamate and taurine concentrations in the extra-cellular space in male rats anesthetized with pentobarbital or isoflurane. Brain injury and edema were evaluated 24 h after ischemia. Isoflurane prevented the ischemia-induced efflux of glutamate and reduced the release of taurine. No difference in the size of the brain lesions was observed with both anesthetics, and isoflurane induced the formation of a bigger brain edema and reduced taurine release. These results suggest that inhibiting glutamate release during ischemia may not be sufficient to improve brain outcome after transient ischemia.

Intraoperative on-line monitoring of cerebral pH by microdialysis in neurosurgical procedures

The objective of this study was to improve the ability to detect cerebrovascular complications in patients undergoing complicated neurosurgical procedures using on-line monitoring of cerebral pH with in vivo microdialysis. We employed on-line pH monitoring in patients with a variety of neurosurgical procedures including high-flow bypass surgery, aneurysm clipping, and temporal resection in epilepsy treatment. The pH was monitored with a microdialysis probe, usually inserted into the frontal cortex and pH of the dialysate was measured on-line with a pH electrode. We monitored 17 cases: 12 high-flow extracranial-intracranial (EC-IC) bypass procedures, 3 surgeries to clip large basilar tip aneurysms under protection of hypothermic circulatory arrest, and 2 surgeries for intractable seizure disorders. In the patients undergoing high-flow bypass, the pH remained stable in 5 patients and all had an uneventful outcome. In 3 patients, the pH decreased during surgery. One patient had a severe hemiparesis on awaking from anesthesia. The fall in pH in another patient was corrected when the blood pressure was raised during surgery. The pH was also responsive to changes in intraoperative ventilation and probably also to brain edema with elevation of pH values. In the three patients undergoing basilar tip aneurysm clipping under hypothermic circulatory arrest, the pH fell to 6.41 in one patient. This patient awoke with a mild hemiparesis. In the other two patients, the pH was stable during the hypothermia and neither patient had complications. In the patients undergoing temporal lobectomy and hippocampectomy, the pH fell rapidly with the onset of ischemia. We conclude that it is possible to monitor the cerebral extracellular pH with on-line microdialysis. The information obtained may alert the surgeon to the possibility of impending cerebral ischemia or other complications. However, further experience is needed before the technique can be recommended for general use.

Current therapeutic methods of dural arteriovenous malformation: Are there any alternatives? Two case reports of infratentorial AVM's

We describe two cases of infratentorial dural AVM, in which a successful surgical intervention was performed. This procedure was chosen as the repeated treatment by embolization proved to be ineffective.Theories as to the pathogenesis of dural AVM, the current treatment as well as options for new therapies are presented.

Clinical Aspects of Microdialysis

Basic Science and Methodology.- Possible Glial Contribution of Rat Hippocampus Lactate as Assessed with Microdialysis and Stress.- Application of Glutamate in the Cortex of Rats: A Microdialysis Study.- Clinical Microdialysis: The Role of On-line Measurement and Quantitative Microdialysis.- Intracerebral Microdialysis Markedly Inhibits the Propagation of Cortical Spreading Depression.- Delayed Neuronal Damage Following Focal Ischemic Injury in Stroke-Prone Spontaneously Hypertensive Rats.- The Measurement of Extracellular Inorganic Phosphate Gives a More Reliable Indication for Severe Impairment of Cerebral Cell Function and Cell Death than the Measurement of Extracellular Lactate.- Clinical Investigations.- A Concept for the Introduction of Cerebral Microdialysis in Neurointensive Care.- Lactic Acid and Amino Acid Fluctuations Measured Using Microdialysis Reflect Physiological Derangements in Head Injury.- Glutamate Release and Cerebral Blood Flow After Severe Human Head Injury.- Increased Levels of Glutamate in Patients with Subarachnoid Haemorrhage as Measured by Intracerebral Microdialysis.- Microdialytic Monitoring of the Cortex During Neurovascular Surgery.- In vivo Microdialysis Study of Extracellular Glutamate Response to Temperature Variance in Subarachnoid Hemorrhage.- Antiepileptic Drug Pharmacokinetics in Patients with Epilepsy Using a New Microdialysis Probe: Preliminary Observations.- A New Screwing Device for Fixing a Microdialysis Probe in Critical Care Patients.- A Novel Microdialysis Probe Designed for Clinical Use: Potential Analytical and Therapeutic Applications.- Microdialytic Monitoring During a Cardiovascular Operation.- Index of Keywords.