Brain Microdialysis as a Tool To Explore the Ionic Profile of the Brain Extracellular Space in Neurocritical Patients: A Methodological Approach and Feasibility Study

Abstract

Our aim is to determine whether the ionic concentration in brain microdialysate enables calculations of the actual Na + , K + , and Cl -concentrations in vitro and whether this method can be applied to determine the ionic concentrations in the brain extracellular fluid. We designed an experiment using CMA-71 probes (M Dialysis, Stockholm, Sweden) and the standard conditions used in a clinical setting. Nine CMA-71 probes were inserted in different matrices and perfused with mock cerebrospinal fluid containing 3% albumin at the standard infusion rate used in the clinical setting (0.3 lL/min). Microvials were replaced every 12 h, and the ionic concentrations, both in the dialysate and the matrix, were analyzed. For each ion, scatter plots were built, with [Na, and [Cl -] in the dialysate as the predictor variables and the matrix concentrations as the outcome variables. A linear regression model allowed us to calculate the true ionic concentrations in the matrix. To demonstrate the feasibility of the method, we present the calculated ionic profile of one patient with a malignant infarction and a second with a severe traumatic brain injury. Our results confirm that the ionic concentration in microdialysate can be used to calculate the true concentrations of ions in a matrix and the actual concentrations in the extracellular fluid. Microdialysis offers the unique possibility of monitoring the dynamic changes of ions in the brain over time and opens a new avenue to explore the brain's ionic profile, its changes in brain edema, and how this profile can be modified with different therapies.

Characterization of the Ionic Profile of the Extracellular Space of the Injured and Ischemic Brain: A Microdialysis Study

“…2 A method of dealing with this shortcoming is to increase the infusion speed from the standard 0.3 µL/min to 0.5 -1.0 µL/min. However, this increase reduces the ionic recovery and therefore decreases the lower limit of detection for K + in some commercial analyzers; this is clinically relevant because [K + ] o is the most relevant biomarker to define brain tissue viability.…”

“…This upper limit was similar to the upper reference levels of 3.6 -4.1 mmol/L in the CSF of controls described by others. 2,3 Is the ionic profile normal in the apparently non-damaged brain?…”

“…Under steady state, the intracellular concentration of potassium ([K + ] i ) in the CNS is typically around 145 mmol/L, and the extracellular potassium concentration ([K + ] o ) is ~3 mmol/L. [1][2][3] Transmembrane sodium gradients have the opposite orientation, and the extracellular concentration of sodium ([Na + ] o ) is much higher that its intracellular concentration ([Na + ] i ). The ATP-dependent Na + /K + -pump of intact brain cells maintains a concentration gradient between the intracellular and extracellular compartments of approximately 1:10.…”

“…2 However, the main limitation of the methodology used in our proof-of-concept study -conventional ion selective electrode based analyzer-was its low temporal resolution. Inductively coupled plasma mass spectrometry (ICP-MS) is a state-of-the art instrumental technique for the analysis of metals including ions at very low concentrations.…”

Reappraisal of the reference levels for energy metabolites in the extracellular fluid of the human brain

“…9,21 The experiments were conducted using an in vitro setup that was described by our group elsewhere. 22 In brief, the experiments involved placing each CMA-71 catheter into two different matrix solutions (MA-1 and MA-2), which had different concentrations of glucose, lactate, pyruvate, and glycerol (Sigma-Aldrich, St Louis, MO, USA). The study matrices composition is described in Table S1 in Supplementary information.…”