Brain Research 881 (2000) 121–127 www.elsevier.com / locate / bres Research report In vivo study of tumor metabolism: an application of new multi-probe microdialysis system in the striatum of freely moving rats grafted with C6 cells a b, c e b b * O. Darbin , M. Lonjon , M.H. Quentien , J.F. Michiels , P. Grellier , J. Negrin , a d J.C. Rostain , J.J. Risso a ´ ´ ´ Universite de la Mediterranee, Laboratoire de barobiologie et de neurochimie des interactions cellulaires, Institut J. Roche, ´ ´ Faculte de medecine Nord. 13916 Marseille Cedex 20 France b Service de neurochirurgie, CHU Pasteur, 30 Avenue de la voie Romaine, 06002 Nice Cedex 01, France c ´ ´ ICNE, Institut J.Roche, Faculte de medecine Nord, 13916 Marseille Cedex 20 France d ´ IMNSSA, Unite de neurochimie, HIA St Anne 83800 Toulon Naval France e Service d’ anatomo-pathologie, CHU Pasteur, 30 Avenue de la voie Romaine, 06002 Nice Cedex 01 France Accepted 20 June 2000 Abstract The purpose of this study is to investigate the in vivo tumoral brain metabolism in free moving rats using microdialysis. Cells from C6 glioma cell line were inoculated in one striatum 15 days before the microdialysis experimentation. Then, using a new system allowing perfusion of several microdialysis probes in free moving rat, normalised dialysate levels of glucose, lactate and pyruvate were monitored in both glioma and control striatum. At the end of the procedure, animals were sacrificed for histological study. Data shows that probe functioning is similar in both tissues. The results for normalised glucose level were in striatum control: 2.14 mM, in tumoral striatum: 1.71 mM (P.0.1); for lactate, respectively, 0.86 and 1.65 mM (P,0.05) and for pyruvate, respectively, 65.56 and 140.94 mM(P,0.05). This data clearly shows a significant increase of pyruvate and lactate in tumoral striatum compared to normal striatum, correlating previous in vitro studies on glioma metabolism. We conclude that this microdialysis technique is of value in tumoral brain and could constitute an interesting tool for a better understanding of glioma metabolism.  2000 Elsevier Science B.V. All rights reserved. Keywords: Glucose; Lactate; Pyruvate; Glioma; Model 1. Introduction tions of extracellular space content in glioma results of indirect data obtained in vivo by the use of techniques such Glioblastoma prognosis is poor, with a median survival as nuclear magnetic resonance (NMR) or Positron Emis- of 50 weeks and 3% survival after 3 years [19]. Therapeu- sion tomography (PET-SCAN) [8,21]. The use of simpler tic improvements requires a better knowledge of tumoral techniques to especially investigate the extracellular con- metabolism. These challenges are linked, at least for a part, tent in trophic or neuromediating agents is relevant in to the development of an in vivo model to study physiolog- neuro-oncology. Microdialysis is a well-established tech- ical characteristics of brain tumoral tissue. nique allowing the analysis of brain extra-cellular fluid in It is now established that allograft or xenograft models laboratory animals. As other in vivo monitoring techniques of brain tumor are relevant to investigate metabolic activity (i.e. voltammetry), the analysis of fluid content can be alterations [12], to test antitumoral agents [17] or to performed in anaesthetised or in free moving subjects. This research abnormal gene expressions [10,16]. Despite these technique is successfully used in several models of brain research strategies, knowledge on modifications of ex- injury [7] and provides the analysis of various compounds tracellular content in tumoral brain remains poorly docu- [3] and especially of energetic metabolites. mented. To date, major knowledge concerning the altera- The brain tissue, under physiological conditions, uses glucose as its major source for energy. Its catabolism takes *Corresponding author. two metabolic ways: (1) glycolysis and (2) oxidative 0006-8993 / 00 / $ – see front matter  2000 Elsevier Science B.V. All rights reserved. PII: S0006-8993(00)02633-0