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Biomedical subjects

R Griebel

Publications and source records attributed to R Griebel.

12 recordsLinked to original sources

Glucose-induced decrease in glutamate levels in ischemic human brain by in-vivo microdialysis.

Glutamate is one of the principal neurotoxins in the pathogenesis of ischemic neuronal injury. Elevated glutamate levels in ischemia have been well documented in many animal stroke models. Recent work in humans also shows a similar trend. We have used our acute focal ischemic model of the human brain to study the response of glutamate levels by in vivo microdialysis during ischemia using two different perfusates. The addition of 30 mM of glucose to the perfusate attenuated the percentages of dialysate glutamate levels from 4.27 +/- 1.7 to 1.34 +/- 0.47 (P < 0.001) during partial ischemia and from 21.42 +/- 6.05 to 7.25 +/- 1.43 (P < 0.05) with total ischemia. The pre-ischemic values of glutamate were similar with the two perfusates. These results indicate that the ischemia-induced rise in glutamate is attenuated by exogenous glucose delivery in the human stroke model.

Amino Acids

In-vivo microdialysis study of extracellular glutamate response to temperature variance in subarachnoid hemorrhage.

Neurochemical changes may precede the development of clinical signs in neurological disease. Early identification of such changes may offer an opportunity to avoid or treat complications. Under experimental conditions, extracellular levels of glutamate and other amino acids can be monitored by in-vivo microdialysis in cerebral ischemia, head trauma and epilepsy. Data on the release of glutamate under ischemic conditions in humans are limited. There is no published data on the effects of temperature variation or other manipulations on the extracellular glutamate levels in humans. We report for the first time, the effects of changes in temperature on the extracellular cerebral glutamate levels as measured by in-vivo microdialysis, the dialysate being collected before, during and after cooling in four patients with subarachnoid hemorrhage. Three of the patients had in-vivo microdialysis carried out postoperatively. One patient underwent microdialysis three days prior to the surgical clipping of the aneurysm. In all patients, mild head cooling resulted in a significant decrease in extracellular glutamate levels. The effect of cooling was most apparent when the extracellular glutamate concentrations were high. In two patients, the extracellular glutamate levels increased sharply with fever but returned to normal once the temperature normalized. In vivo microdialysis can be used to measure extracellular glutamate and other neurotransmitters with minimal discomfort in awake humans. This technique offers a unique opportunity to monitor the neurochemistry in critically ill patients and it may aid in developing therapeutic intervention strategies to minimize undesired chemical responses.

Cold Temperature

Evaluation of monoaminergic neurotransmitters in the acute focal ischemic human brain model by intracerebral in vivo microdialysis.

The release of neurotransmitters principally glutamate during cerebral ischemia has been extensively studied. It is well recognized that ischemia induced release of glutamate plays a key role in "excitotoxic" neuronal death. The role of monoaminergic neurotransmitters is however unclear. The purpose of this study was to evaluate the extracellular norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA) and serotonin (5-HT) under varied degrees of ischemia in the acute focal ischemic model of the human brain by in-vivo microdialysis. The ischemic response of these amines was correlated with the glutamate levels. Our study concludes that these amines and metabolites can be detected in the human "stroke" model. No marked fluctuations were noted in the levels of norepinephrine and DOPAC. However, significant changes to partial and total ischemia were noted in the extracellular levels of 5-HIAA and 5-HT. These compounds showed a dramatic increase with the onset of ischemia with higher detectable levels in the partial ischemic state in comparison to the total ischemic dialysate levels. The exact role played by the differential increase in the levels of 5-HT to the other catecholamines in the pathogenesis of ischemic neuronal damage remains unclear and warrants further study.

3,4-Dihydroxyphenylacetic Acid

Intracerebral human microdialysis. In vivo study of an acute focal ischemic model of the human brain.

BACKGROUND AND PURPOSE: In vivo microdialysis was introduced in 1982 as a technique to study cerebral neurochemistry in awake, freely moving animals. In small animals, bilateral carotid occlusion produces a 7- to 10-fold increase in extracellular glutamate concentrations. This rapidly falls with reperfusion. Increase in extracellular glutamate is currently believed to be a major factor in initiating neuronal injury. Glutamate antagonists are currently undergoing clinical trials in acute stroke. Human data on the extracellular levels of glutamate and other amino acids in the normal or ischemic brain are limited. In this communication we wish to report the extracellular concentrations of glutamate, serine, glutamine, glycine, taurine, alanine, and gamma-aminobutyric acid, as monitored by in vivo microdialysis, in the simulated ischemic model of the temporal lobe of the human brain. METHODS: Intracerebral microdialysis was carried out in five patients who underwent resection of the temporal lobe for intractable epilepsy. Surgical excision leads to an acute (from partial to total, ie, from incomplete to complete) ischemic state of the resected brain. This was our model to study the changes in human extracellular fluid during acute focal ischemic conditions. RESULTS: Extracellular glutamate concentrations were 15 to 30 mumol/L in the preischemic samples. This increased to 380.69 +/- 42.14 mumol/L with partial (incomplete) ischemia and reached a peak of 1781.67 +/- 292.34 mumol/L (> 100-fold) with total isolation of the temporal pole (complete ischemia). The levels fell to 394.52 +/- 72.93 mumol/L 20 minutes after resection. Similar trends were observed with the onset of ischemia in the dialysate levels of serine, glutamine, glycine, alanine, taurine, and gamma-aminobutyric acid. CONCLUSIONS: Our results show that there is a significant increase in extracellular glutamate and other neurotransmitters with ischemia in the temporal lobe model of the human brain. This increase is of a higher magnitude than that in small animals.

Amino Acids

Cerebral malignant tumors with ependymal and choroidal differentiation in two siblings.

Two siblings in a family without a history of phacomatosis or cerebral tumors developed malignant tumors in the posterior fossa at age 28 months and in the left cerebral hemisphere at age 15 months, respectively. Dual ependymal and choroid plexus epithelium differentiation was established by histological, ultrastructural, and immunocytochemical studies. The development of this rare tumor in siblings suggests an inherited predisposition, a common environmental insult, or both.

Brain Neoplasms

CSF shunt complications: an analysis of contributory factors.

The complications arising from 195 shunting procedures are described and correlated with patient and operative variables. Neither the patient's age, sex, type of hydrocephalus, length of surgery, nor the use of prophylactic antibiotics correlated significantly with subsequent shunt complications. However, the surgeon performing the procedure and the type of shunt used were highly significant correlates.

Adolescent

Hemorrhagic changes in experimental spinal cord injury models.

Early hemorrhagic changes in the spinal cord were compared in three experimental spinal cord injury models in the rat in order to determine the nature and consistency of spinal cord hemorrhage following specific and quantitated forces of injury. The spinal cords were injured by weight-dropping, aneurysm clip and extradural balloon compression techniques. Hemorrhagic changes were assessed quantitatively by the image analyser at 1 and 3 hours after injury. Tissue damage was assessed by determining the percentage of total cross sectional area containing hemorrhage. The extent of hemorrhage at site of injury in the clip and balloon preparations was equal, but several times lower in the weight-drop induced injury. Within each experimental group no appreciable differences were observed at the site of injury between the 1 and 3 hours preparations. The variability of damage within experimental groups was most in the weight-dropping and balloon and least in the clip preparations. Differences were also indicated with respect to the distribution of hemorrhage in grey versus white matter. These findings may be of significance when functional recovery is considered in various experimental acute spinal cord injury models.

Animals

Subdural empyema: a retrospective study of 15 patients.

Subdural empyema is a surgical emergency, which, if not recognized and managed promptly, is rapidly fatal. The clinical features, diagnosis, infecting organisms, treatment and results in 15 patients with subdural empyema admitted to the University and Saskatoon City hospitals between 1956 and 1982 are evaluated. There were 11 males and 4 females; 80% were under 50 years of age. Paranasal sinusitis in six patients was the most common cause of the condition. The most frequent presenting features were fever, headache, vomiting, seizures and motor deficit. Preoperative diagnostic methods included skull roentgenography, cerebrospinal fluid studies, electroencephalography, cerebral angiography and computerized tomography. Cultures of the pus were positive for bacteria in 13 of the 15 patients. Drainage of the empyema was accomplished through multiple burr holes, craniotomy and craniectomy. Follow-up ranged from 1 month to 15 years. Eleven patients recovered with minimal or no neurologic deficit, 2 patients had permanent major deficits and 2 died. Successful management of subdural empyema depends on early diagnosis, prompt evacuation of the pus and appropriate antibiotic therapy.

Adolescent

Acute spinal cord injury in the rat: comparison of three experimental techniques.

Three techniques to produce experimental spinal cord injuries in the rat are compared; 1) the weight dropping method, 2) the aneurysm clip compression method and 3) the extradural balloon compression method. In principle, different forces were used in technique one, while a constant force for different durations is maintained in techniques two and three. The relationship between these different types of injuries and subsequent clinical recovery was assessed quantitatively by the inclined plane method of Rivlin and Tator. The weight dropping technique was found unreliable for experimental spinal cord injury in the rat while the aneurysm clip compression technique resulted in consistent cord injuries with respect to subsequent clinical recovery. The extradural balloon compression method invariably resulted in complete recovery after three and five minutes but no recovery after seven minutes of 0.1 cc air inflated balloon compression of the cord indicating a steep dose--response curve. However, using a 0.2 cc air inflated balloon, no recovery was noted after one minute compression. The major factor in the pathogenesis of spinal cord injury produced by the weight dropping technique is believed to be mechanical, while both mechanical and vascular factors seem to operate in the clip and balloon compression techniques.

Animals