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. even after a long implantation period. Qualitative and quantitative histological Cycloheximide pontent inhibitor tissue analysis revealed no continuous glial scar formation around the cOFM probe 30 days after implantation and only a minor tissue reaction regardless of Cycloheximide pontent inhibitor perfusion of the probe. Introduction 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]. Histological studies have frequently reported a glial scar, a tissue reaction that surrounds long-term implanted probes. The dense nature of the scar tissue hampers substance transport and therefore 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. Compared to biofouling, the glial scar has a 3C5 times higher impact on decreasing transport of small substances [3]. The precise mechanisms that Cycloheximide pontent inhibitor influence the extent of tissue response to artificial implants are not completely understood [2], [4]C[7]. 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]. Cerebral open flow microperfusion (cOFM) is a relatively new sampling technique based on conventional open flow microperfusion [10]C[13] that allows sampling of large and lipophilic substances in brain interstitial fluid with an intact blood-brain barrier (BBB) to measure substance transport across the BBB. All materials used in the design of cOFM probes are chosen in order to minimize tissue reaction and glial scar formation. Compared to MD Cycloheximide pontent inhibitor sampling, cOFM sampling is not based on a membrane and allows direct, unfiltered mixing of perfusate and interstitial brain fluid. Avoiding a membrane also minimizes adhesion of cells and substances to PLCG2 the probe’s surface, avoids cell migration into a membrane, and reduces continuous irritation of surrounding tissue that is caused by the jagged MD membrane surface [14], [15]. The functional principle of cOFM is very similar to that of push-pull perfusion which was one of the first techniques developed to sample in brain tissue. A major drawback of push-pull perfusion is severe tissue damage around the probe [16], [17]. In the present study we aimed to evaluate the long-term effect of cOFM probe materials and design in regard to brain tissue reaction with a focus on day 15 after cOFM probe implantation, at which time BBB is reestablished [18]. We compared the histology of brain tissue around the cOFM probe with na? ve frontal lobe tissue of the contralateral hemisphere and studied the effects of probe implantation and perfusion. Materials and Methods Animals All animal protocols used in this study were approved by the Austrian Ministry of Science and Research (Ref.II/10b, Vienna). A total of 36 adult male Sprague Dawley rats (Harlan Laboratories, Udine, Italy) with a weight of 300C450 g were used in this study. Animals were allowed to acclimatize to the environment for at least one week after transportation before any surgical procedures were carried out. After probe implantation animals were housed individually in acrylic glass cages with a 1212 h lightdark cycle, and food and water were available em ad libitum /em . Appropriate animal care was provided by the staff at the animal care facility (Institute for Biomedical Research, Medical University of Graz, Austria). cOFM probe The cOFM probe (Fig. 1) consists of a 20 Ga fluorinated ethylene propylene (FEP) guide cannula that is inserted into the brain tissue and a healing dummy that provides mechanical stability during implantation. The healing dummy also prevents tissue ingrowth into the guide cannula during the healing period. The space between healing dummy and guide cannula that is needed for insertion and extraction of the dummy also allows the flexible guide.