The Cerebral Extracellular Release of Glycerol, Glutamate, and FGF2 Is Increased in Older Patients following Severe Traumatic Brain Injury

Abstract

Old age is associated with a poor recovery from traumatic brain injury (TBI). In a retrospective study we investigated if the biochemical response following TBI is age dependent. Extracellular fluids were continuously sampled by microdialysis in 69 patients admitted to our NSICU following severe TBI. The concentrations of glycerol, glutamate, lactate, pyruvate, and eight different cytokines (IL-1b, IL-6, IL-10, IL-8, MIP-1b, RANTES, FGF2, and VEGF) were determined by fluorescence multiplex bead technology. Patients in the oldest age group ( ‡ 65 years) had significantly higher microdialysate concentrations of glycerol and glutamate compared to younger patients: the mean microdialysate concentration of glycerol increased from 55.9 lmol/L (25-44 year) to 252 lmol/L ( ‡ 65 years; p < 0.0001); similarly glutamate increased from 15.8 mmol/L to 92.2 mmol/L ( p < 0.0001). The lactate-pyruvate ratio was also significantly higher in the patients ‡ 65 years of age (63.9) compared with all the other age groups. The patterns of cytokine responses varied. For some cytokines (IL-1b, IL-10, and IL-8) there were no differences between age groups, while for others (MIP-1b, RANTES, VEGF, and IL-6) some differences were observed, but with no clear correlation with increasing age. For FGF2 the mean microdialysate concentration was 43 pg/mL in patients ‡ 65 years old, significantly higher compared to all other age groups ( p < 0.0001). Increased concentrations of glycerol and glutamate would indicate more extensive damaging processes in the elderly. An increase in concentration of FGF2 could serve a protective function, but could also be related to a dysregulation of the timing in the cellular response in elderly patients.

Cerebrospinal Fluid and Microdialysis Cytokines in Severe Traumatic Brain Injury: A Scoping Systematic Review

“…Of the 19 articles included in the CMD cytokine portion of the systematic review (11–19), 15 were formal manuscript publications (14–24, 26–29) and 4 were meeting abstract publications (11–13, 25). There were 13 prospective studies (13–16, 18–21, 25–29), with 12 prospective observational studies (13–15, 18–21, 25–29) and 1 prospective randomized control trial (16).…”

“…Four studies were retrospective case series or database reviews (11, 20, 22, 23). Finally, two studies were of “unknown” study design given a lack of information available within the methods (12, 24). …”

FGF-2 released from degenerating neurons exerts microglial-induced neuroprotection via FGFR3-ERK signaling pathway

“…The brain concentration of FGF2 is reported to be around 30 to 120 ng/mg [46]; however, some reports show that the concentration is around 50 pg/ml [47,48]. In a future study, we will attempt to clarify the effect of 100 ng/ml FGF2 in vivo .…”

Creating a “Prosurvival Phenotype” Through Histone Deacetylase Inhibition

“…In a study that used cerebral microdialysis in pigs undergoing TBI and HS, we found that treatment with FFP + VPA infusion led to a decrease in cerebral lactate and pyruvate compared with the FFP alone group, implying superior glucose utilization for ATP production. We also noted a decrease in concentrations of glutamate in the brains of the FFP+ VPA animals, a known excitotoxic neurotransmitter implicated as the final common pathway in neuronal injury and death (86), and glycerol, a well-established marker of membrane-phospholipid damage after TBI (87, 88). These findings suggest an overall decrease in excitotoxicity and brain damage.…”