Abstract
This study investigated the histological tissue reaction to long-term implanted cerebral open flow microperfusion (cOFM) probes in the frontal lobe of the rat brain. Most probe-based cerebral fluid sampling techniques are limited in application time due to the formation of a glial scar that hinders substance exchange between brain tissue and the probe. A glial scar not only functions as a diffusion barrier but also alters metabolism and signaling in extracellular brain fluid. cOFM is a recently developed probe-based technique to continuously sample extracellular brain fluid with an intact blood-brain barrier. After probe implantation, a 2 week healing period is needed for blood-brain barrier reestablishment. Therefore, cOFM probes need to stay in place and functional for at least 15 days after implantation to ensure functionality. Probe design and probe materials are optimized to evoke minimal tissue reaction even after a long implantation period. Qualitative and quantitative histological tissue analysis revealed no continuous glial scar formation around the cOFM probe 30 days after implantation and only a minor tissue reaction regardless of perfusion of the probe.
Highlights
Implantable microelectrodes, biosensors and sampling probes are used to investigate the metabolism and the chemical composition of the interstitial fluid in brain tissue
We found no tissue on any of the probes which would have caused underestimation of glial scarring in the remaining tissue section
Conclusion cerebral open flow microperfusion (cOFM) is a new technique for sampling the interstitial brain fluid
Summary
Implantable microelectrodes, biosensors and sampling probes are used to investigate the metabolism and the chemical composition of the interstitial fluid in brain tissue. All of these devices critically depend on substance exchange with the surrounding tissue [1]. The dense nature of the scar tissue hampers substance transport and the function of implanted probes [2]. Glial scar formation and biofouling on probe surfaces and interface membranes are major factors decreasing probe performance over time. The glial scar has a 3–5 times higher impact on decreasing transport of small substances [3]. Though all invasive techniques cause implantation stress, perfusion probes like microdialysis (MD) or push-pull perfusion have additional stress factors caused by the chemical properties of the perfusate or shear forces due to perfusate flow [8,9]
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