Table 7. Glucose utilization increases 5–6-fold and greatly exceeds lactate utilization after electrical stimulation of hippocampal dentate gyrus in vivoa.

Experimental interval	Glucose	Lactate
Concentration in extracellular fluid (ECF), resting rat brain (μmol/mL)b	2.6	0.75
Resting glucose utilization rate (CMRglc) in dentate gyrus in vivo (μmol/g per min)c	0.66
12 seconds interval following the first 5 seconds electrical stimulation
Percentage decrease in ECF concentration after stimulationd	20	7
Amount consumed from ECF (μmol/mL)d	0.52	0.05
Glc delivered to the resting brain from blood during 12 seconds (μmol/mL)c	0.13	–
Total Glc consumed from ECF + minimum Glc delivered; lac lost from ECF (all as Glc equivalents, μmol/mL)e	0.65	0.025
Calculated utilization rate during 12 seconds (all as glucose equivalents, μmol/g per min)	3.25	0.13
Minimum relative increase in CMRglc after first stimulus compared with rest in vivo	4.9-fold
Maximal lactate utilization as percentage of total lactate + glucose utilization	4%
12 seconds interval following subsequent 5 seconds electrical stimuli
Interinterval extracellular fluid concentration (μmol/mL)f	2.08	1.28
Percentage decrease in ECF concentration after stimulationf	10–20	28
Amount consumed from ECF (μmol/mL)d	0.21–0.42	0.36
Glc delivered to the resting brain from blood during 12 seconds (μmol/mL)c	0.13	–
Glc equivalent of net interinterval increase in ECF lactate level (μmol/mL) (i.e., glucose consumed that is converted to lactate and released to ECF)f	0.26	–
Total Glc consumed=(ECF loss + minimum Glc delivered + Lac accumulated in ECF); Lac consumed=loss from ECF (all as Glc equivalents, μmol/mL)f	0.60–0.81	0.18
Calculated utilization rate during 12 seconds (all as glucose equivalents, μmol/g per min)f	3.0–4.05	0.9
Minimum relative increase CMRglc after subsequent stimuli compared with rest in vivof	4.5–6.1-fold
Maximal lactate utilization as percentage of total lactate + glucose utilizatione	22–30%

^aHu and Wilson (1997b) implanted glucose (Glc) and lactate (Lac) sensors into the dentate gyrus of the rat hippocampus, gave single or repeated electrical stimuli of 5-second duration, and measured temporal changes in extracellular glucose and lactate levels that were reported as percentage of the respective control values; actual concentrations were not stated. Shorter stimuli (1, 2, 3 seconds) did not produce detectable changes in lactate level, and those after 4 seconds were minor and variable.

^bExtracellular fluid (ECF) brain glucose level is from Hu and Wilson (1997a) who used the same glucose sensor and experimental paradigm as did Hu and Wilson (1997b); absolute values for extracellular lactate were estimated as follows. Values for total brain tissue lactate level in various regions of normal resting rat brain range from ∼0.2 to 0.6 μmol/g in our laboratory (Dienel et al, 2002, 2007a; Cruz and Dienel, 2002); similar percentage increases also occur in the human brain (Mangia et al, 2007b). To allow for higher interlaboratory values up to ∼1 μmol/g, an intermediate value for resting brain [lac]=0.75 was used for calculations in this table. For simplicity, extracellular and intracellular Glc and Lac levels are taken to be equivalent, with the caveat that extracellular Glc would be somewhat higher than intracellular Glc, whereas the converse would be true for Lac. All ECF lactate is assumed to be derived from metabolism of brain glucose. Where stated, lactate (Lac) concentration is divided by 2 to obtain glucose (Glc) equivalents of lactate.

^cGlucose utilization rate is the average of mean values from four subregions of the dentate gyrus of conscious rats from the study of Wree et al, 1993. Glucose delivery to the resting brain is equal to glucose utilization rate at steady state; glucose delivered during a 12-second interval is (0.66 μmol/g per min)(0.2 minutes)=0.13 μmol/g. This value does not include the additional stimulus-induced increases in delivery and metabolism of blood-borne glucose and of any brain glycogen consumed; calculated Glc utilization rates (CMR_glc) are, therefore, minimal values.

^dPercentage changes in ECF concentrations at ∼12 seconds after the 5-seconds electrical stimulus are from Hu and Wilson, 1997b. Derived values were calculated from estimated initial concentrations and % changes.

^eMinimal glucose utilization rate over a 12-second interval after a 5-second electrical stimulus was estimated as total Glc equivalents consumed (i.e., for the first stimulus: net decrease in extracellular Glc + Glc delivered to the resting brain; for subsequent stimuli: net Glc decrease + Glc delivered + Glc equivalents of Lac accumulated) divided by 0.2 minutes. It must be noted that minimal CMR_glc values after the first or subsequent stimuli are about 5–6-fold higher than normal resting rate. As this increase greatly exceeds values generally observed after very strong physiological stimuli (approximately 50–100%), the 5-second electrical stimulus may have induced local seizure activity. Calculated lactate utilization rate was based only on the net fall in lactate level, which may not be due only to metabolism, i.e., some lactate release to blood and lactate diffusion beyond the range of the sensor can contribute to a decrease in concentration; lactate utilization estimates are, therefore, maximal rates. Thus, calculated lactate utilization rates expressed as percentages of the calculated glucose plus lactate utilization rates are overestimates.

^fThe increase in extracellular lactate level during subsequent stimuli ranged from 140 to 200% of the basal level (Hu and Wilson, 1997b), and a mean of 170% was used to calculate the higher level after repeated stimuli; new basal ECF glucose level was set at 20% below the initial resting value, and transient decrements were set at 10–20% of the lower basal glucose level. The increase in basal lactate level is attributed to glucose metabolism to lactate and release to ECF. Calculations were made as described for the first stimulus, except that the glucose equivalent to the increase in ECF lactate is included in the CMR_glc total. This calculation also does not include the likelihood that CMR_glc increased between the subsequent stimuli, because interinterval ECF glucose level fell by 0.52 μmol/mL from 2.6 to 2.08 μmol/mL even though blood flow and glucose delivery probably also increased.