On-line continuous intraoperative monitoring of human brain function during a neurosurgical aneurysm procedure

S35 frequency-dependent inhibition (FDI), a reflection of one aspect of this circuit, is reduced following HFS. Here we examined whether this type of plasticity is affected by aging. Young (up to 12 months) and old ( > 18 months) rats were prepared for acute recording of field potentials in the dentate gyrus. FDI was measured before and 45 min after HFS. There was no difference in the magnitude of LTP but only in the young rats was a significant reduction in FDI obtained. The results indicate that this type of local circuit plasticity is compromised in aging. EFFECT OF PRENATAL STRESS ON SYMPATHOADRENAL ACTIVITY IN RATS AT REST AND IN RESPONSE TO FOOTSHOCK R. McCarty1, D. Men1, T. Poltyrev2, D. Schorer-Apelbaum2 and M. Weinstock2 Dept. of Psychology1, University of Virginia, Charlottesville, Virginia, USA and Dept. of Pharmacology2, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel The effect of prenatal stress was investigated on the sympathoadrenal response to novelty and footshock by measuring the time course of the changes in circulating corticosterone (COR) catecholamines and their metabolites. Pregnant rats were subjected to noise stress, 3 times weekly on an unpredictable basis throughout gestation. Their male offspring (PS) and that of unstressed mothers (C) aged 4.5–5 months were prepared with indwelling catheters in the tail artery, 24 h before the experiment. Resting levels of plasma COR, noradrenaline (NA), adrenaline (AD), dihydroxyphenglycol (DHPG), dihydroxyphenylacetic acid (DOPAC) and dihydroxy phenylalanine (DOPA) were measured. Further blood samples were taken within 3 min after their transfer to the shock box, 1–2, 5, 15 and 45 min after footshock. Plasma COR was significantly higher in PS than in C rats at rest, but that of AD and NA did not differ. Transfer of the rats to the shock box increased plasma COR, NA, AD and DHPG in both groups. These catechols, DOPAC and DOPA increased further immediately after footshock. The increments in plasma NA and DHPG and DOPAC were significantly higher in PS than in C rats. The findings are indicative of greater activation of tyrosine hydroxylase in the sympathetic nerves and adrenal of PS rats. The results demonstrate for the first time that prenatal stress can induce longterm changes in the sensitivity of the sympathoadrenal system to stress. Since similar effects on plasma catecholamines are seen after injections of corticotropin releasing hormone into the amygdala, they may result from higher levels and activity of the peptide in PS rats. ON-LINE CONTINUOUS INTRAOPERATIVE MONITORING OF HUMAN BRAIN FUNCTION DURING A NEUROSURGICAL ANEURYSM PROCEDURE S. Meilin1, E. Ornstein3, N. Razon2, G.E. Ouaknine2 and A. Mayevsky1 1 Dept. of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel; 2 Dept. of Neurosurgery, Tel-Aviv Med. Center, Tel-Aviv, Israel; 3 Dept. of Anesthesiology, Columbia Presbyterian Medical Center, New York, USA Many attempts were made to monitor a single parameter in the OR (EEG, evoked potentials, CBF). Those approaches did not provide enough real-time interpretive data to follow the complicated multifactorial pathophysiology of the brain. After modifications and adjustments of the multiparametric monitoring system (Mayevsky et al., J. Basic and Clin. Physiol. Pharmacol. 1: 207–220, 1990) we developed the Brain Viability Probe – BVP – which enabled routine monitoring of the following parameters from the cerebral cortex of the human brain: CBF, mitochondrial NADH redox state, ECoG and brain temperature. The Brain Viability Probe (BVP) was sterilized and used during 34 operation procedures (tumor removal, aneurysm). Preliminary results accumulated in the OR in response to changes in the end-tidal CO2 were published (Mayevsky et al., J. CBF Metabol. 17 Suppl. 1 S591,

1997). The evaluation of five patients who underwent aneurysm surgery are presented in this study. These patients exhibited different levels of ischemia-like responses during the surgical procedure, which were expressed in the decrease in CBF followed by an immediate increase in NADH. This study demonstrates that the BVP can be used successfully for concomitant monitoring of different brain parameters during neurosurgery and that aneurysm surgery itself may induce different degrees of transient ischemia. This monitoring device may be used as an alarm system for avoiding irreversible brain damage due to ischemia. Supported by the Chief Scientist’s Office, Ministry of Health, Israel. FUSION OF PRION PROTEIN TO GREEN FLUORESCENT PROTEIN FACILITATES SUBCELLULAR LOCALIZATION Z. Meiner, Y. Rosental, M. Vey, S. Pilkuhn, and S.B. Prusiner Depts. of Neurology, Hadassah University Hospital, Jerusalem, Israel, and University of California, San Francisco, CA, USA PrPc, the normal isoform of the prion protein, plays a key role in the pathogenesis of prion diseases. Defining the subcellular localization and trafficking of PrPC is likely to be important for elucidating the function of PrPC and the mechanism by which it is converted into PrPSc, the pathological isoform. To localize PrPC in normal (N2a) and scrapie-infected (ScN2a) neuroblastoma cells, we created fusion proteins consisting of PrP and the fluorescent marker, Green Fluorescent Protein (GFP). The fusion proteins (GFP-PrPs) were transiently expressed in both N2a and ScN2a cells, and analyzed in living and fixed cells using fluorescence and confocal microscopy and FACS analysis. The fluorescent fusion proteins were detected on the plasma membrane of the cell soma, neurites, and in perinuclear compartments in both N2a and ScN2a cells. Immunofluorescent detection of endogenous PrP demonstrated a similar intracellular localization which was localized to the trans-Golgi network (TGN) by comparison with other markers of the TGN including TGN38 and furin. Like endogenous PrPC, phosphoinositol-specific phospholipase-C treatment released the majority of the fusion proteins from the cell surface. Therefore, these fusion proteins traffic in a manner similar to that of endogenous PrPC, making them useful for studying PrP metabolism. In addition to the known localization on the plasma membrane, GFP-PrP was found in the axonodendritic tree and the TGN. These findings may be important for understanding the function of PrP and the mechanism of conversion of PrPC into PrPSc. Using the fusion protein we investigated whether mutations in PrP cause differences in subcellular localization of the protein. Data regarding the mutant PrP, PrPE200K will be presented. RESPONSES OF HEMODYNAMIC, METABOLIC, IONIC AND ELECTRICAL ACTIVITIES IN THE CEREBRAL CORTEX TO INTRACRANIAL PRESSURE ELEVATION IN A RAT MODEL E. Michaely, A. Mayevsky Dept. of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel Intracranial hypertension occurring in most patients exposed to traumatic head injury, is a major cause of morbidity and mortality in such patients. Previous studies showed that an increase in intracranial pressure (ICP) is associated with a decrease in microvascular blood flow and in some cases a decrease in high energy compounds measured in brain tissue or blood samples. Earlier brain monitoring under increased ICP didn’t include mitochondrial NADH redox state or extracellular ion concentration. In the present study we used the MPA Multiprobe Assembly, developed in our laboratory, which enabled in situ and real-time measurement of mitochondrial NADH (using a fiberoptic fluorometer), blood flow (Laser Doppler Flowmeter), ICP (Camino probe), ECoG, brain temperature and K+, Ca2+ and H+ extracellular concentration. Male rats (230–250 g) were operated upon; after brain exposure and dura removal, the MPA was located on the brain surface and cemented with dental acrylic. The femoral artery was can-