Mechanisms of peritumoural brain dysfunction: metabolic and neuroreceptor findings in striatal C6 glioma.
The aetiology of the peritumoural brain dysfunction that is rectified by steroids is unknown. To determine potential aspects of its pathophysiological basis we performed metabolic, histochemical and neuroreceptor studies in rodents with striatal C6 glioma. This model is known to cause focal neurobehavioural and electrophysiological dysfunction. The fully quantitative [(14)C]-2-deoxyglucose autoradiographic technique of measuring local cerebral metabolism of glucose (LCMRglu) showed raised LCMRglu (22-29%) in the pallidum, substantia nigra and endopeduncular nucleus. Acetylcholinesterase (AChE) histochemistry and a range of ligand binding studies for dopamine type 1 and 2, and serotonergic 5-HT(2)receptors were negative in the tumour and normal in peritumoural brain. 5-HT uptake sites and strong peripheral benzodiazepine receptor expression were present in the tumour. There was extensive up-regulation of peripheral benzodiazepine receptor expression in the peritumoural brain. These studies show there is metabolic dysregulation in brain regions functionally connected to, but anatomically distant from the striatum. There is also a peritumoural region of up-regulated receptors that have many, predominantly inhibitory, functions. The relationship of these findings to peritumoural brain dysfunction is discussed.
Whittle
I R
IR
Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, UK. irw@skull.dcn.ed.ac.uk
Kelly
P A
PA
D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D001345:Autoradiography; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D003847:Deoxyglucose / Q000493:pharmacokinetics; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism*; D014316:Tritium
D002250:Carbon Radioisotopes; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A; D011985:Receptors, Serotonin; D014316:Tritium; D003847:Deoxyglucose; D000110:Acetylcholinesterase