3fb3ec55d8a3b7febca96073ee086f92 cells-13-02112.pdf d6d24120efe1d43c1e2af12c22e3650665fe0e73 cells-13-02112.pdf 8d8f21e61ed9f19a9a738b2a4bfb2c1afefd169f06a93ee51d390bc020d1b591 cells-13-02112.pdf Title: A Combinatory Therapy of Metformin and Dexamethasone Reduces the Foreign Body Reaction to Intraneural Electrodes Subject: Neural electrodes used for bidirectional communication between the nervous system and external devices like prosthetic limbs have advanced in neuroprosthetic applications. However, their effectiveness is hindered by the foreign body reaction, a natural immune response causing inflammation and fibrosis around the implanted device. This process involves protein adsorption, immune cell recruitment, cytokine release, and fibroblast activation, leading to a fibrous capsule formation and a decrease in electrode functionality. Anti-inflammatory and antifibrotic strategies have the potential to diminish the impact of the foreign body response. In this work, we have evaluated long-term metformin administration and short-term dexamethasone administration as a combined therapy to modulate the foreign body reaction induced by a polyimide intraneural implant in the sciatic nerve of rats. After a 12-week implant, the foreign body reaction was significantly reduced only in the group administered both drugs. Keywords: foreign body reaction; neuroprostheses; metformin; dexamethasone; macrophages; fibroblasts Author: Bruno Rodríguez-Meana, Jaume del Valle and Xavier Navarro Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Fri Dec 20 09:46:46 2024 CET ModDate: Fri Dec 20 09:59:57 2024 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 22954461 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- WLENKM+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 YNUJMA+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 VQGBER+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 MVIDWN+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 AEITLL+VnURWPalladioL Type 1 Custom yes yes yes 32 0 CAMXTK+EURM10 Type 1 Builtin yes yes yes 62 0 LRTYNE+CMSY10 Type 1 Builtin yes yes yes 70 0 LGIPOF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 98 0 LGIPOG+PalatinoLinotype CID TrueType Identity-H yes yes yes 101 0 LGIPOH+PalatinoLinotype TrueType WinAnsi yes yes no 107 0 LGIPOJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 110 0 LGJADI+PalatinoLinotype TrueType MacRoman yes yes no 113 0 LGIPOF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 142 0 LGIPOG+PalatinoLinotype CID TrueType Identity-H yes yes yes 145 0 LGIPOH+PalatinoLinotype TrueType WinAnsi yes yes no 151 0 LGIPOJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 154 0 LGJADI+PalatinoLinotype TrueType MacRoman yes yes no 157 0 LGJBMA+PalatinoLinotype,Italic TrueType MacRoman yes yes no 160 0 LGIPOF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 205 0 LGIPOG+PalatinoLinotype CID TrueType Identity-H yes yes yes 208 0 LGIPOH+PalatinoLinotype TrueType WinAnsi yes yes no 214 0 LGIPOJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 217 0 LGJADI+PalatinoLinotype TrueType MacRoman yes yes no 220 0 LGIPOF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 244 0 LGIPOG+PalatinoLinotype CID TrueType Identity-H yes yes yes 247 0 LGIPOH+PalatinoLinotype TrueType WinAnsi yes yes no 253 0 LGIPOJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 256 0 LGJADI+PalatinoLinotype TrueType MacRoman yes yes no 259 0 LGIPOF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 274 0 LGIPOG+PalatinoLinotype CID TrueType Identity-H yes yes yes 277 0 LGIPOH+PalatinoLinotype TrueType WinAnsi yes yes no 283 0 LGIPOJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 286 0 LGJADI+PalatinoLinotype TrueType MacRoman yes yes no 289 0 MNANBH+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 320 0 MNANBJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 323 0 MNANBK+PalatinoLinotype CID TrueType Identity-H yes yes yes 326 0 MNANBL+PalatinoLinotype TrueType WinAnsi yes yes no 332 0 MNANCM+PalatinoLinotype TrueType MacRoman yes yes no 335 0 LGIPOF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 357 0 LGIPOG+PalatinoLinotype CID TrueType Identity-H yes yes yes 360 0 LGIPOH+PalatinoLinotype TrueType WinAnsi yes yes no 366 0 LGIPOJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 369 0 LGJADI+PalatinoLinotype TrueType MacRoman yes yes no 372 0 LGIPOF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 387 0 LGIPOG+PalatinoLinotype CID TrueType Identity-H yes yes yes 390 0 LGIPOH+PalatinoLinotype TrueType WinAnsi yes yes no 396 0 LGIPOJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 399 0 LGJADI+PalatinoLinotype TrueType MacRoman yes yes no 402 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-02-15 02:46:24 CET RepresentationInformation: cells-13-02112.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-02-12 07:38:49 CET Size: 22954461 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 643 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Surgical Procedure Destination: subsection.2.1 Item: Title: Drug Administration Destination: subsection.2.2 Item: Title: Electrophysiological and Functional Evaluation Destination: subsection.2.3 Item: Title: Histological Evaluation Destination: subsection.2.4 Item: Title: Data Analysis Destination: subsection.2.5 Item: Title: Results Destination: section.3 Children: Item: Title: Functional Evaluation Destination: subsection.3.1 Item: Title: Inflammatory Response Destination: subsection.3.2 Item: Title: Capsule Formation Destination: subsection.3.3 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: A Combinatory Therapy of Metformin and Dexamethasone Reduces the Foreign Body Reaction to Intraneural Electrodes Author: Bruno Rodríguez-Meana, Jaume del Valle and Xavier Navarro Subject: Neural electrodes used for bidirectional communication between the nervous system and external devices like prosthetic limbs have advanced in neuroprosthetic applications. However, their effectiveness is hindered by the foreign body reaction, a natural immune response causing inflammation and fibrosis around the implanted device. This process involves protein adsorption, immune cell recruitment, cytokine release, and fibroblast activation, leading to a fibrous capsule formation and a decrease in electrode functionality. Anti-inflammatory and antifibrotic strategies have the potential to diminish the impact of the foreign body response. In this work, we have evaluated long-term metformin administration and short-term dexamethasone administration as a combined therapy to modulate the foreign body reaction induced by a polyimide intraneural implant in the sciatic nerve of rats. After a 12-week implant, the foreign body reaction was significantly reduced only in the group administered both drugs. Keywords: foreign body reaction; neuroprostheses; metformin; dexamethasone; macrophages; fibroblasts Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Fri Dec 20 09:46:46 CET 2024 ModDate: Fri Dec 20 09:59:57 CET 2024 ID: 0xef05f454eb9b791ac9c448f7e2282717, 0xef05f454eb9b791ac9c448f7e2282717 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: YNUJMA+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 122 FontDescriptor: FontName: YNUJMA+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: AEITLL+VnURWPalladioL FontSubset: true FirstChar: 160 LastChar: 226 FontDescriptor: FontName: AEITLL+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: VQGBER+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 169 FontDescriptor: FontName: VQGBER+URWPalladioL-Roma 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