Neuro-inflammatory Sequelae of Minimal Trauma in the Non-traumatized Human Brain: A Microdialysis Study

Abstract

Cytokine measurement directly from the brain parenchyma by means of microdialysis has documented the activation of certain procedures in vivo, after brain trauma in humans. However, the intercalation of the micro-catheter insertion with the phenomena triggered by the head trauma renders the assessment of the findings problematic. The present study attempts to elucidate the pure effect of minimal trauma, represented by the insertion of the micro-catheter, on the non-traumatized human brain. Microdialysis catheters were implanted to twelve patients with drug-resistant epilepsy, subjected to invasive electroencephalogram recording with intracranial electrodes. Samples were collected during the first 5 days of monitoring. The dialysate was analyzed using bead flow cytometry, and the concentrations of IL-1, IL-6, IL-8, IL-10, IL-12, and TNFa were measured. The levels of IL-1 and IL-8 were found raised until 48 hours post-implantation and thereafter they reached a plateau of presumably basic values. The temporal profile of the IL-6 variation was different, the raise being much prolonged, as its concentration had not returned to basic levels at the fifth day post-insertion. TNFa was found significantly raised only 2 hours after the implantation. Interleukins 10 and 12 did not present any significant response to micro-trauma. These findings, probably more clearly detected in an environment disengaged by the sequelae of severe brain injury, imply that the reaction of the neuro-inflammatory mechanisms of the brain exists even after minimal trauma and is unexpectedly intense concerning IL-6. This response concerns also IL-1, IL-8 and TNFa, while IL-10 and IL-12 may necessitate more severe injuries to be activated. An approach to the question of basic cytokine levels in the normal brain parenchyma is attempted. Finally, questions may rise regarding the objectivity of findings attributed by some studies to inflammatory perturbation after head injury.

Update: Microdialysis for Monitoring Cerebral Metabolic Dysfunction after Subarachnoid Hemorrhage

“…Hence, it is crucial to understand how each of these variables affects the extraction fraction while interpreting the CMD data to avoid underestimation. Moreover, probe implementation can cause an inflammatory response by damaging the brain tissue surrounding it [ 76 ]. Accordingly, ISF samples collected within a short period of time after probe implementation may not accurately reflect the metabolic changes, only acute inflammation, and should be discarded.…”

Electroosmotic Perfusion, External Microdialysis: Simulation and Experiment

“…Thus, only very slow reactions are accessible with these devices. In addition, the diameter of these devices at ∼350 μm inhibits application to small brain regions and creates significant insertion trauma. − Iontophoresis has been used sparingly for analogous work. Qualitative evaluation of peptide hydrolysis following iontophoretic delivery into skin has been investigated for Tyr-Phe, LHRH, and delta sleep-inducing peptide .…”