Influence of probe flexibility and gelatin embedding on neuronal density and glial responses to brain implants.

To develop long-term high quality communication between brain and computer, a key issue is how to reduce the adverse foreign body responses. Here, the impact of probe flexibility and gelatine embedding on long-term (6w) tissue responses, was analyzed. Probes of same polymer material, size and shape, flexible mainly in one direction, were implanted in rat cerebral cortex (nimplants = 3 x 8) in two orientations with respect to the major movement direction of the brain relative to the skull: parallel to (flex mode) or transverse to (rigid mode). Flex mode implants were either embedded in gelatin or non-embedded. Neurons, activated microglia and astrocytes were visualized using immunohistochemistry. The astrocytic reactivity, but not microglial response, was significantly lower to probes implanted in flex mode as compared to rigid mode. The microglial response, but not astrocytic reactivity, was significantly smaller to gelatin embedded probes (flex mode) than non-embedded. Interestingly, the neuronal density was preserved in the inner zone surrounding gelatin embedded probes. This contrasts to the common reports of reduced neuronal density close to implanted probes. In conclusion, sheer stress appears to be an important factor for astrocytic reactivity to implanted probes. Moreover, gelatin embedding can improve the neuronal density and reduce the microglial response close to the probe

Nanowire biocompatibility in the brain - Looking for a needle in a 3D stack

We investigated the brain-tissue response to nanowire implantations in the rat striatum after 1, 6, and 12 weeks using immunohistochemistry. The nanowires could be visualized in the scar by confocal microscopy (through the scattered laser light). For th

Visualization of the probe used for implantation, implantation modes and regions of interest for image analysis.

<p>A) Schematic overview of the probe. Images are not to scale. B) Shanks were inserted 1 mm caudal and 2.3 mm lateral to Bregma (B, Bregma), either sagittal (rigid mode, 1) or coronal (flex mode, 2). (L, Lambda). C) Two regions of interests (ROIs) were analyzed in NIS Elements 3.1 software (Nikon, Japan), measuring 0–50 μm (inner ROI, marked with a red line) and 50–200 μm (outer ROI, marked with a green line) from the estimated border of the hole left by the implant.</p

Implantation mode and embedding dependent glial reactions.

<p>A) Representative images of rigid, flex and flex embedded mode implantations after 6 weeks, showing mode dependent alterations in astrocytosis, as shown in red (GFAP), microglia responses, as shown in green (ED1) and merged (DAPI in blue (total cell nuclei)). Scale bar: 50 μm. Cephalocaudal direction corresponds to top-to-bottom in image. B and C) Quantification of the GFAP and ED1 densities, respectively, that surrounds the different implantation sites in the inner ROI (0–50 μm). The box corresponds to the 25th and 75th percentiles, the median value is indicated by the horizontal line within each box, and the whiskers show the minimum and maximum values. The horizontal lines indicate statistical differences.</p

Effects on neuronal density and morphology.

<p>A) Representative images of rigid, flex and flex embedded mode implantations after 6 weeks, showing mode dependent alterations neuronal densities, as shown in green (NeuN), total cell nuclei (DAPI) in blue and merged (GFAP in red depicting the implantation scar). Scale bar: 50 μm. B and C) Quantification of the NeuN and DAPI densities, respectively, that surrounds the different implantation sites at the inner ROI (0–50 μm). Note that in B) the NeuN densities are compared to paired naïve areas (controls). The box corresponds to the 25th and 75th percentiles, the median value is indicated by the horizontal line within each box, and the whiskers show the minimum and maximum values. The horizontal lines indicate statistical differences.</p