Influence of Probe Flexibility and Gelatin Embedding on Neuronal Density and Glial Responses to Brain Implants

Abstract

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.

Ultrasoft microwire neural electrodes improve chronic tissue integration

“…3F and H) could possibly be explained by a previous study reporting that a rigid cylindrical implant tethered to the skull caused oval scarring [97]. The author suggested the principle direction of brain movement relative to the skull of freely moving rodents may strongly influence the tissue response and the principle direction of brain movement caused more pressure to the cell body shape towards that direction [98]. Our analyses using automated algorithms confirmed that the neurons around the stiff implant had a much higher CSSI than those around the soft wires, and the CEA of cell body deformation was well aligned with predicted strain direction.…”

Histological evaluation of flexible neural implants; flexibility limit for reducing the tissue response?

“…In vitro cell viability studies pertaining to mechanotransduction also suggested that excessive strain conditions decrease neuronal viability [15], whereas soft substrates allow for preferential attachment and growth of neurons over glial cells [16]. Based on these initial findings, many groups shifted gears toward developing probes made of softer materials than silicon, including polyimide [8,17], parylene [18,19], SU-8 [20,21], nanocomposites [14,[22][23][24], and other materials [25][26][27][28][29].…”

Local delivery of minocycline-loaded PLGA nanoparticles from gelatin-coated neural implants attenuates acute brain tissue responses in mice

“…We have previously reported that gelatin can be used as a coating-material to provide structural support during implantation of ultrathin flexible electrodes in the brain [5,33] and that gelatin itself can significantly reduce microglia activation but not the astrocytic response [4,6]. Here we developed a novel method for local delivery of nanoparticles from gelatin coatings allowing the amount of drug to be kept several orders of magnitude lower as compared to systemic administration.…”

“…We have previously shown that the mechanical properties, such as flexibility, size, anchoring and specific weight of the electrodes are of key importance [2][3][4][5]. However, it was only when combining ultra-flexible mechanical properties with a gelatin embedding that the ubiquitous loss of nearby neurons was, for the first time, abolished [4]. Moreover, we recently found that gelatin coating promotes healing of the blood-brain barrier [6].…”