Biology subjects

Spira, M. E.

Publications and source records attributed to Spira, M. E..

3 recordsLinked to original sources

bioRxiv2022

Significantly reduced inflammatory foreign-body-response to neuroimplants and improved recording performance in young compared to adult rats

The multicellular inflammatory encapsulation of implanted intracortical multielectrode arrays (MEA) is associated with severe deterioration of their field potentials (FP) recording performance, which thus limits the use of brain implants in basic research and clinical applications. Therefore, extensive efforts have been made to identify the conditions in which the inflammatory foreign body response (FBR) is alleviated, or to develop methods to mitigate the formation of the inflammatory barrier. Here, for the first time, we show that (1) in young rats (74{+/-}8 gr, 4 weeks old at the onset of the experiments), cortical tissue recovery following MEA implantation proceeds with ameliorated inflammatory scar as compared to adult rats (242 {+/-}18 gr, 9 weeks old at the experimental onset); (2) in contrast to adult rats in which the Colony Stimulating factor 1 Receptor (CSF1R) antagonist chow eliminated ~95% of the cortical microglia but not microglia adhering to the implant surfaces, in young rats the microglia adhering to the implant were eliminated along with the parenchymal microglia population. The removal of microglia adhering to the implant surfaces was correlated with improved recording performance by in-house fabricated Perforated Polyimide MEA Platforms (PPMP). These results support the hypothesis that microglia adhering to the surface of the electrodes, rather than the multicellular inflammatory scar, is the major underlying mechanism that deteriorates implant recording performance, and that young rats provide an advantageous model to study months-long, multisite electrophysiology in freely behaving rats.

neuroscience↗

bioRxiv2022

Efficacy and sex differences in the effects on rat brain microglia of the colony-stimulating factor 1 receptor inhibitor-PLX5622

Microglia play pivotal roles in central nervous system development, homeostasis, responses to trauma, neurodegenerative and neuropsychiatric disorders with significant sex-bias in their symptoms and prevalence. The discovery that the survival of microglia in adult brains depends on the expression of the colony-stimulating factor 1 receptor (CSF1R), along with the development of the effective brain permeant CSF1R inhibitors PLX5622, has boosted the investigation of the role of microglia in health, disease and in relations to sex-bias. The effectiveness of PLX5622 in examining the role of microglia has mainly been demonstrated in mice. Surprisingly, despite the critical importance of rat models in brain research, there are only 4 publications in which PLX5622 was used to investigate the roles of microglia in adult rats. This has been attributed to the "impression" that PLX5622 is "ineffective in rats". In view of the importance and interest in the role of microglia, the indispensability of rats for in vivo electrophysiological brain studies and behavioral research and the high efficacy of PLX5622-chow in eliminating microglia from adult mice brains, we examined the effects of PLX5622-chow on the elimination of the microglia in adult female and male rats. We found significant differences in microglia elimination by ad libitum PLX5622 feeding in male and female rats in different brain regions with significantly greater effectivity in female brains. Our pragmatic study provides practical information on the use and design of PLX5622 in gender-related and rat brain preclinical microglia research.

neuroscience↗

bioRxiv2021

Ultrastructural analysis of neuroimplant-parenchyma interfaces uncover remarkable neuroregeneration along-with barriers that limit the implant electrophysiological functions

Despite increasing use of in-vivo multielectrode array (MEA) implants for basic research and medical applications, the critical structural interfaces formed between the implants and the brain parenchyma, remain elusive. Prevailing view assumes that formation of multicellular inflammatory encapsulating-scar around the implants (the foreign body response) degrades the implant electrophysiological functions. Using gold mushroom shaped microelectrodes (gMEs) based perforated polyimide MEA platforms (PPMPs) that in contrast to standard probes can be thin sectioned along with the interfacing parenchyma; we examined here for the first time the interfaces formed between brains parenchyma and implanted 3D vertical microelectrode platforms at the ultrastructural level. Our study demonstrates remarkable regenerative processes including neuritogenesis, axon myelination, synapse formation and capillaries regrowth in contact and around the implant. In parallel, we document that individual microglia adhere tightly and engulf the gMEs. Modeling of the formed microglia-electrode junctions suggest that this configuration suffice to account for the low and deteriorating recording qualities of in vivo MEA implants. These observations help define the anticipated hurdles to adapting the advantageous 3D in-vitro vertical-electrode technologies to in-vivo settings, and suggest that improving the recording qualities and durability of planar or 3D in-vivo electrode implants will require developing approaches to eliminate the insulating microglia junctions.

neuroscience↗