Pharmacological Mitigation of Tissue Damage during Brain Microdialysis

Abstract

Microdialysis sampling in the brain is employed frequently in the chemical analysis of neurological function and disease. But, implanting the probes, which are substantially larger than the size and spacing of brain cells and blood vessels, is injurious and triggers ischemia, gliosis, and cell death at the sampling site. The nature of the interface between the brain and the microdialysis probe is critical to the use of microdialysis as a neurochemical analysis technique. The objective of the work reported here was to investigate the potential of two compounds, dexamethasone, a glucocorticoid anti-inflammatory agent, and XJB-5-131, a mitochondrially-targeted reactive oxygen species scavenger, to mitigate the penetration injury. Measurements were performed in the rat brain striatum, which is densely innervated by axons that release dopamine, an electroactive neurotransmitter. We used voltammetry to measure electrically evoked dopamine release next to microdialysis probes during the retrodialysis of dexamethasone or XJB-5-131. After the in vivo measurements, the brain tissue containing the microdialysis probe tracks was examined by fluorescence microscopy using markers for ischemia, neuronal nuclei, macrophages, and dopamine axons and terminals. Dexamethasone and XJB-5-131 each diminished the loss of evoked dopamine activity, diminished ischemia, diminished the loss of neuronal nuclei, diminished the appearance of extravasated macrophages, and diminished the loss of dopamine axons and terminals next to the probes. Our findings confirm the ability of dexamethasone and XJB-5-131 to mitigate, but not eliminate, the effects of the penetration injury caused by implanting microdialysis probes into brain tissue.

Enhancing Continuous Online Microdialysis Using Dexamethasone: Measurement of Dynamic Neurometabolic Changes during Spreading Depolarization

“…Recent work on the microdialysis of dopamine in the rat striatum shows that DEX reduces ischemia, suppresses glial activation, protects neurons and neuronal terminals, and reinstates normal dopamine activity in the tissues surrounding microdialysis probes. [32][33][34][35][36] Here, we report that DEX also offers substantial benefits to the microdialysis of SDassociated glucose and K + transients in the rat cortex. We inserted microdialysis probes into the cortex of rats and monitored glucose and K + 2 hrs, 5 days, or 10 days later.…”

“…The insertion SD supports prior conclusions that probe insertion causes a penetration injury. [28][29][30][31][32][33][34][35][36][37][38][39][40][41] Two additional examples of complete recordings of K + and glucose from single animals are provided in the Supplementary Information document. Figure S1 is an example with needle pricks that produced neither a K + spike nor a glucose dip.…”

“…Previous studies from the rat striatum have established that probe insertion triggers ischemia in the vicinity of the probe and that a glial barrier eventually surrounds and engulfs the probe, thereby hindering long-term sampling. [28][29][30][31][32][33][34][35][36] Adding DEX to the perfusion fluid reduces ischemia and suppresses gliosis. Consistent with these prior reports, the present study confirms that DEX retrodialysis enhances the performance of microdialysis monitoring also in the rat cortex.…”

“…Figure 8 extends our previous reports that DEX prevents ischemia and gliosis. [32][33] Figure 8 is our first report that DEX prevents ischemia and gliosis near probes inserted into the rat cortex, that the benefits of DEX last for 10 days after insertion, and that the benefits of DEX retrodialysis long outlast the DEX retrodialysis itself.…”

“…[26][27] Nevertheless, inserting the probe into brain tissue causes a penetration injury. [28][29][30][31][32][33][34][35] In response, the host tissue engulfs the probe in a glial barrier that, once formed, impairs further microdialysis sampling. 32,[36][37][38][39][40][41] This is a limitation for clinical microdialysis, as TBI patients often remain under intensive care for 10 days or more.…”