Acute Depression of Energy Metabolism after Microdialysis Probe Implantation is Distinct from Ischemia-Induced Changes in Mouse Brain

Abstract

The current study used measurements of metabolites and markers of membrane integrity to determine the most suitable time point for microdialysis experiments following probe implantation. Leakage of Evans blue and sodium fluorescein indicated increased BBB permeability only immediately (15 min), but not 1.5 and 24 h following probe implantation. Acute implantation decreased glucose and lactate levels relative to the levels after 24 h (to 13-37% and 25-60%, respectively). No change in extracellular levels of glutamate or glycerol was seen. In comparison to acute probe implantation, the pattern of damage under brain ischemia (middle cerebral artery occlusion) differed: While glucose levels dropped, lactate levels rose after ischemia, and glutamate (tenfold) and glycerol (eightfold) increased sharply. In conclusion, acute implantation of a microdialysis probe causes transient depression of the energy metabolites, glucose and lactate, likely due to injury-induced hypermetabolism. However, no massive tissue damage or severe ischemic conditions around the probe occur.

Post-traumatic hypoxia exacerbates neurological deficit, neuroinflammation and cerebral metabolism in rats with diffuse traumatic brain injury

“…We expected post-TAI hypoxia to aggravate the metabolic disarray caused by diffuse axonal injury and employed the microdialysis technique to monitor changes of various metabolites over 4 days. Due to the detection of significant alterations in brain metabolites following the implantation of microdialysis probe in uninjured sham animals as reported by others [63], we chose to discard samples over the first 20 h following probe implantation to reduce the artifact from the needle injury. In this study we were only present data of glucose, lactate and glutamate from the microdialysates, since pyruvate is known to become unstable after prolonged storage time (CMA Microdialysis).…”

“…We therefore allowed the rats to recover for 4 hours after TAI before implanting the microdialysis probe. In accordance with others [63], our study has shown that in sham rats energy metabolism is altered during the first 24 h following microdialysis probe implantation, therefore we chose to examine only the data from 20 h onwards to reduce the "probe effect".…”

Pathophysiology, treatment, and animal and cellular models of human ischemic stroke

“…Both oxygen-derived free radicals and reactive nitrogen species are involved in activating several pathways involved in cell death following stroke, such as apoptosis and inflammation [37-39]. A reduction of oxygen supply also leads to the accumulation of lactate via anaerobic glycolysis and so to acidosis [40-43]. …”

In vivo cerebral microdialysis validation of the acute central glutamate response in a translational rat model of concussion combining force and rotation

“…However, the absence of any distinguishable difference in implanted hippocampal tissue visualized under cresyl violet-photomicrograph across concussion and sham groups as well as the stability of ECF GABA levels throughout all dialysate sampling times suggest that only slight, if any, additional damage to hippocampal tissue could be attributed to leaving the microdialysis probe inserted during impact 27 . Alternatively, having kept the probe inserted throughout the entire experimental procedure significantly reduced the likelihood of inducing repeated damage associated with microdialysis probe insertion, including damage to the mTBI-sensitive blood-brain barrier 28 . Interestingly, a one-time probe insertion into healthy brain tissue has been shown to leave the blood-brain barrier intact 28 .…”

“…Alternatively, having kept the probe inserted throughout the entire experimental procedure significantly reduced the likelihood of inducing repeated damage associated with microdialysis probe insertion, including damage to the mTBI-sensitive blood-brain barrier 28 . Interestingly, a one-time probe insertion into healthy brain tissue has been shown to leave the blood-brain barrier intact 28 . Perhaps most importantly, uninterrupted dialysate collection throughout the entire experimental procedure allowed us to include a gold standard tissue recovery and equilibration period before beginning sample collection 29 .…”