Cyst Fluid From Cystic, Malignant Brain Tumors: A Reservoir of Nutrients, Including Growth Factor-Like Nutrients, for Tumor Cells

Neurosurgery 80:917–924, 2017

Brain tumors may have cysts, whose content of nutrients could influence tumor cell microenvironment and growth.

OBJECTIVE: To measure nutrients in cyst fluid from glioblastoma multiforme (GBM) and metastatic brain tumors.

METHODS: Quantification of nutrients in cyst fluid from 12 to 18 GBMs and 4 to 10 metastatic brain tumors.

RESULTS: GBM cysts contained glucose at 2.2 mmol/L (median value; range <0.8-3.5) and glutamine at 1.04 mmol/L (0.17-4.2). Lactate was 7.1 mmol/L (2.4-12.5) and correlated inversely with glucose level (r = –0.77; P < .001). Amino acids, including glutamate, varied greatly, but median values were similar to previously published serum values. Ammonia was 75 μmol/L (11-241). B vitamins were present at previously published serum values, and riboflavin, nicotinamide, pyridoxal 5 -phosphate, and cobalamin were higher in cyst fluid than in cerebrospinal fluid. Inorganic phosphate was 1.25 mmol/L (0.34-3.44), which was >3 times higher than in ventricular cerebrospinal fluid: 0.35 mmol/L (0.22-0.66; P < .001). Tricarboxylic acid cycle intermediates were in the low micromolar range, except for citrate, which was 240 μmol/L (140-590). In cystic metastatic malignant melanomas and lung tumors values were similar to those in GBMs.

CONCLUSION: Tumor cysts may be a nutrient reservoir for brain tumors, securing tumor energy metabolism and synthesis of cell constituents. Serum is one likely source of cyst fluid nutrients. Nutrient levels in tumor cyst fluid are highly variable, which could differentially stimulate tumor growth. Cyst fluid glutamate, lactate, and phosphate may act as tumor growth factors; these compounds have previously been shown to stimulate tumor growth at concentrations found in tumor cyst fluid.

 

Relationship between intracranial hemodynamics and microdialysis markers of energy metabolism and glutamate-glutamine turnover in patients with subarachnoid hemorrhage

J Neurosurg 111:910–915, 2009.DOI: 10.3171/2008.8.JNS0889

The aim of this study was to explore the relationship between hemodynamics (intracranial and systemic) and brain tissue energy metabolism, and between hemodynamics and glutamate (Glt)-glutamine (Gln) cycle activity.

Methods. Brain interstitial levels of lactate, pyruvate, Glt, and Gln were prospectively monitored in the neurointensive care unit for more than 3600 hours using intracerebral microdialysis in 33 patients with subarachnoid hemorrhage (SAH). Intracranial pressure (ICP), mean arterial blood pressure, and cerebral perfusion pressure (CPP) were recorded using a digitalized system.

Results. Interstitial Gln and pyruvate correlated with CPP (r = 0.25 and 0.24, respectively). Intracranial pressure negatively correlated with Gln (r = −0.29) and the Gln/Glt ratio (r = –0.40). Levels of Gln and pyruvate and the Gln/Glt ratio were higher and levels of Glt and lactate and the lactate/pyruvate ratio were lower during periods of decreased ICP (≤ 10 mm Hg) as compared with values in periods of elevated ICP (> 10 mm Hg). In 3 patients, a poor clinical condition was attributed to high ICP levels (range 15–25 mm Hg). When CSF drainage was increased and the ICP was lowered to 10 mm Hg, there was an instantaneous sharp increase in interstitial Glt and pyruvate in these 3 patients.

Conclusions. Increasing interstitial Gln and pyruvate levels appear to be favorable signs associated with improved CPP and low ICP. The authors suggest that this pattern indicates an energy metabolic situation allowing augmented astrocytic energy metabolism with accelerated Glt uptake and Gln synthesis. Moreover, their data raised the question of whether patients with SAH and moderately elevated ICP (15–20 mm Hg) would benefit from CSF drainage at lower pressure levels than what is usually indicated in current clinical protocols.