title: Chronic intracortical microelectrode arrays induce non-uniform, depth-related tissue responses.
abstract: OBJECTIVE
  Brain-implanted microelectrode arrays show promise as future clinical devices. However, biological responses to various designs, compositions and locations of these implants have not been fully characterized, and may impact the long-term functionality of these devices. In order to improve our understanding of the tissue conditions at the interface of chronic brain-implanted microdevices, we proposed utilizing advanced histology and microscopy techniques to image implanted devices and surrounding tissue intact within brain slices. We then proposed utilizing these methods to examine whether depth within the cerebral cortex affected tissue conditions around implants.
  
  
  METHODS
  Histological data was collected from rodent brain slices containing intact, intracortical microdevices four weeks after implantation surgery. Thick tissue sections containing the chronic implants were processed with fluorescent antibody labels, and imaged in an optical clearing solution using laser confocal microscopy.
  
  
  RESULTS
  Tissue surrounding microdevices exhibited two major depth-related phenomena: a non-uniform microglial coating along the device length and a dense mass of cells surrounding the implant in cerebral cortical layers I and II. Detailed views of the monocyte-derived immune cells improve our understanding of the close and complex association that immune cells have with chronic brain implants, and illuminated a possible relationship between cortical depth and the intensity of a chronic monocyte response around penetrating microdevices. The dense mass of cells contained vimentin, a protein not typically expressed highly in CNS cells, evidence that non-CNS cells likely descended down the face of the penetrating devices from the pial surface.
  
  
  CONCLUSIONS
  Image data of highly non-uniform and depth-dependent biological responses along a device provides novel insight into the complexity of the tissue response to penetrating brain-implanted microdevices. The presented work also demonstrates the value of in situ histological collection of brain implants for studying the complex tissue changes that occur, and the utility of pairing thick-tissue histology with appropriate optical clearing solutions.
authors: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907-2032, USA. awoolley@purdue.edu
authors: Andrew J
authors: AJ
authors: Woolley
authors: Himanshi A
authors: HA
authors: Desai
authors: Kevin J
authors: KJ
authors: Otto
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000502:physiology; D004567:Electrodes, Implanted / Q000009:adverse effects*; D004867:Equipment Design; D005347:Fibroblasts / Q000378:metabolism; D005456:Fluorescent Dyes; D007091:Image Processing, Computer-Assisted; D008264:Macrophages / Q000502:physiology; D008297:Male; D008839:Microelectrodes / Q000009:adverse effects*; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000502:physiology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D014746:Vimentin / Q000096:biosynthesis
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D005456:Fluorescent Dyes; D008840:Microfilament Proteins; D014746:Vimentin