Assessment of Global Ischemia - Animal Models of Acute Neurological Injuries: Injury and Mechanistic Assessments - page 360

A carrier solution (physiological solution called perfusate) is
continuously circulating in the probe and substances present in the
interstitial space diffuse into the perfusate making its chemical
composition similar to that of the cerebral environment. As the
solution exits the probe (now called dialysate), it is collected and
analyzed for its components.
This technique is often used to detect cerebral ischemia in ani-
mals ( 23, 26-30 ) and in humans ( 31-34 ), after SAH. It does so by
measuring the markers of glucose metabolism (energy-related
metabolites) and of excitotoxicity. Since during ischemia there is an
increase in anaerobic glucose metabolism (glycolysis) leading to
rise in lactate and fall in pyruvate and glucose, the concentration of
these metabolites in dialysate is used to detect ischemic
cerebral environment. In addition, lactate to pyruvate ratio (L/P)
and lactate to glucose (L/G) ratios are used to refl ect the intracel-
lular redox state, and hypoxic/ischemic glycolysis; respectively.
Glutamate rise is considered an index of cerebral ischemia and
excitotoxicity; especially in animals. Table 1 lists normal concentra-
tion of energy-related cerebral metabolites in rat.
Using this technique, in animals, decrease in cerebral glucose,
increased in lactate/pyruvate ratio and glutamate is noted within
minutes after SAH (Fig. 2 ) ( 23, 26 ). In patients, increased cerebral
lactate/pyruvate ratio, and glutamate is found 24-48 h after SAH
( 31-34 ).
Advantages of cerebral microdialysis are: (1) it is a simple way
of sampling cerebral environment, (2) it does not require removal
of body fl uids and hence allows repeated sampling on same animal.
Thereby, animal requirement is decreased and measurements are
not tainted by changes in fl uid balance or disturbance in blood
homeostasis, (3) it allows sampling in anesthetize and in awake
freely moving animals (chronic sampling), and (4) since dialysate

Table 1
Normal concentrations of energy-related cerebral metabo-
lites and glutamate in microdialysis samples from rat
collected at the perfusate fl ow rate of 2 m l/min ( 39, 40, 48 )

Analyte Concentration

Glucose (mM) 2-3

Pyruvate ( μ M) 8-15

Lactate (mM) 0.6-0.8

Lactate:pyruvate ratio 15-30

Glutamate ( μ M) 2-6