Real-time monitoring of brain energy metabolism in vivo using microelectrochemical sensors: the effects of anesthesia

Abstract

Ž. Ž Rats were implanted in the striatum with a PtrIr electrode for measurement of regional cerebral blood flow rCBF H clearance 2 . technique , a carbon paste electrode for monitoring tissue oxygen and a glucose biosensor for monitoring extracellular glucose. Changes Ž . Ž in all three parameters were recorded in response to the intraperitoneal i.p. administration of the anesthetics chloral hydrate 350 . Ž . Ž . mgrkg , sodium pentobarbitone 60 mgrkg and ketamine 200 mgrkg . An i.p. injection of normal saline, given as a control for the injection of the anesthetics, produced a parallel increase in rCBF and tissue oxygen accompanied by a brief decrease in extracellular glucose. Changes in tissue oxygen reflected the changes in rCBF; there was a decrease in both after sodium pentobarbitone, a decrease followed by a rebound after ketamine and a transient increase after chloral hydrate. All three anesthetics produced a decrease in extracellular glucose. The disparity between the changes in glucose and the changes in rCBF and oxygen suggests that during anesthesia, the reduction in extracellular glucose is not due to a reduction in the direct delivery of glucose from the blood vascular system. These results also indicate that levels of enzymatic substrates and mediators, which are intrinsic to the design and operation of amperometric biosensors, are clearly altered in a complex manner by anesthesia and suggest that caution should be exercised in extrapolating data from acute anesthetized experiments to normal physiology. q

Simultaneous recording of hippocampal oxygen and glucose in real time using constant potential amperometry in the freely-moving rat

“…The suppression of neural activity by anaesthesia and its effects on glucose in the brain has been previously demonstrated using a number of different anaesthetic agents, including chloral hydrate (Fellows et al, 1992;Fillenz and Lowry, 1998b;Lowry et al, 1998a;Lowry and Fillenz, 2001;Uematsu et al, 2009;Horn and Klein, 2010). Our data for hippocampal oxygen follows the same patterns observed in the striatum during chloral hydrate anaesthesia, namely an increase in tissue levels of oxygen during the period of anaesthesia with a return to baseline levels following the return to consciousness (Bolger and Lowry, 2005).…”

“…Using implantable sensors allows for stable, long-term recording of a number of common analytes in the extracellular fluid (ECF) of the brain including oxygen (Lowry et al, 1996Lowry and Fillenz, 2001;Bolger and Lowry, 2005), glucose (Hu and Wilson, 1997;Fillenz and Lowry, 1998a;Lowry et al, 1998a,b,c;Lowry and Fillenz, 2001;Dixon et al, 2002), nitric oxide (Brown et al, 2009) and glutamate (Kulagina et al, 1999;McMahon et al, 2006aMcMahon et al, , 2006bMcMahon et al, , 2007Qin et al, 2008;Tian et al, 2009). Unlike other methods implanted into the brain tissue (Clark et al, 1958;Krolicki and Leniger-Follert, 1980;Doppenberg et al, 1998;Gupta et al, 1999).…”

Brain nitric oxide: Regional characterisation of a real-time microelectrochemical sensor

“…We have previously reported a significant but short lived change (22 ± 3 pA, p < 0.001, n = 9) from baseline levels in NO sensor's implanted in the striatum of Wistar rats following saline injection (Finnerty et al, 2012). Similar initial and brief injection effects have also been observed for tissue O 2 (Bolger et al, 2011) and regional cerebral blood flow (rCBF) (Lowry and Fillenz, 2001) during the injection of saline, with a comparable return to baseline levels. A significant increase in the recorded current (13 ± 3 pA, p < 0.001, n = 17) was observed in the prefrontal cortex, reaching a maximum level after 5 ± 1 min (n = 17) and returning to a baseline level after 12 ± 2 min.…”

Characterization in vitro and in vivo of the oxygen dependence of an enzyme/polymer biosensor for monitoring brain glucose

“…3A demonstrates a high O 2 sensitivity even at moderate glucose levels, the question remained whether Pt/PPD/GOx electrodes might be suitable for monitoring brain glucose, where the estimated level is much lower than in blood. ECF glucose in rat striatum has been determined by both quantitative microdialysis: 3509/20 mM (Fray et al, 1997), 3509/16 mM (Lowry et al, 1998a) and 710 mM (McNay et al, 2001) and biosensor data: 300 Á/400 mM (Lowry and Fillenz, 2001) in the awake rat.…”

“…Anaesthetic doses of Ketamine have been shown recently to cause biphasic changes in brain ECF pO 2 (Lowry and Fillenz, 2001), and so we used this drug to investigate further the O 2 interference question. Ketamine (200 mg/kg, i.p., see Fig.…”