Pharmacological mitigation of tissue damage during brain microdialysis.
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.
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Kathryn M
KM
Nesbitt
Andrea
A
Jaquins-Gerstl
Erin M
EM
Skoda
Peter
P
Wipf
Adrian C
AC
Michael
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D003497:Cyclic N-Oxides / Q000008:administration & dosage*; D003907:Dexamethasone / Q000008:administration & dosage*; D004298:Dopamine / Q000032:analysis; D020197:Head Injuries, Penetrating / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D017551:Microdialysis / Q000009:adverse effects* / Q000295:instrumentation; D051381:Rats
D003497:Cyclic N-Oxides; C523959:XJB-5-131; D003907:Dexamethasone; D004298:Dopamine