Improved Functional Recovery in Rat Spinal Cord Injury Induced by a Drug Combination Administered with an Implantable Polymeric Delivery System
Spinal cord injury (SCI) is an incurable condition, in which a cascade of cellular and molecular events triggered by inflammation and excitotoxicity impairs endogenous regeneration, namely remyelination and axonal outgrowth. We designed a treatment solution based on an implantable biomaterial (elect...
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| Veröffentlicht in: | Journal of neurotrauma 2020-08, Vol.37 (15), p.1708-1719 |
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| creator | Bighinati, Andrea Focarete, Maria Letizia Gualandi, Chiara Pannella, Micaela Giuliani, Alessandro Beggiato, Sarah Ferraro, Luca Lorenzini, Luca Giardino, Luciana Calzà, Laura |
| description | Spinal cord injury (SCI) is an incurable condition, in which a cascade of cellular and molecular events triggered by inflammation and excitotoxicity impairs endogenous regeneration, namely remyelination and axonal outgrowth. We designed a treatment solution based on an implantable biomaterial (electrospun poly (l-lactic acid) [PLLA]) loaded with ibuprofen and triiodothyronine (T3) to counteract inflammation, thus improving endogenous regeneration.
efficacy was tested by implanting the drug-loaded PLLA in the rat model of T8 contusion SCI. We observed the expected recovery of locomotion beginning on day 7. In PLLA-implanted rats (i.e., controls), the recovery stabilized at 21 days post-lesion (DPL), after which no further improvement was observed. On the contrary, in PLLA + ibuprofen (Ibu) + T3 (PLLA-Ibu-T3) rats a further recovery and a significant treatment effect were observed, also confirmed by the gait analysis on 49 DPL. Glutamate release at 24 h and 8 DPL was reduced in PLLA-Ibu-T3- compared to PLLA-implanted rats, such as the estimated lesion volume at 60 DPL. The myelin- and 200-neurofilament-positive area fraction was higher in PLLA-Ibu-T3-implanted rats, where the percentage of astrocytes was significantly reduced. The implant of a PLLA electrospun scaffold loaded with Ibu and T3 significantly improves the endogenous regeneration, leading to an improvement of functional locomotion outcome in the SCI. |
| doi_str_mv | 10.1089/neu.2019.6949 |
| format | Article |
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efficacy was tested by implanting the drug-loaded PLLA in the rat model of T8 contusion SCI. We observed the expected recovery of locomotion beginning on day 7. In PLLA-implanted rats (i.e., controls), the recovery stabilized at 21 days post-lesion (DPL), after which no further improvement was observed. On the contrary, in PLLA + ibuprofen (Ibu) + T3 (PLLA-Ibu-T3) rats a further recovery and a significant treatment effect were observed, also confirmed by the gait analysis on 49 DPL. Glutamate release at 24 h and 8 DPL was reduced in PLLA-Ibu-T3- compared to PLLA-implanted rats, such as the estimated lesion volume at 60 DPL. The myelin- and 200-neurofilament-positive area fraction was higher in PLLA-Ibu-T3-implanted rats, where the percentage of astrocytes was significantly reduced. The implant of a PLLA electrospun scaffold loaded with Ibu and T3 significantly improves the endogenous regeneration, leading to an improvement of functional locomotion outcome in the SCI.</description><identifier>ISSN: 0897-7151</identifier><identifier>EISSN: 1557-9042</identifier><identifier>DOI: 10.1089/neu.2019.6949</identifier><identifier>PMID: 32212901</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Astrocytes ; Biomaterials ; Contusions ; Excitotoxicity ; Gait ; Gamma rays ; Ibuprofen ; Inflammation ; Laboratory animals ; Locomotion ; Medical research ; Myelin ; Myelination ; Neurodegeneration ; Nonsteroidal anti-inflammatory drugs ; Polylactic acid ; Recovery of function ; Regeneration ; Spinal cord injuries ; Thyroid hormones ; Transplants & implants ; Trauma ; Triiodothyronine</subject><ispartof>Journal of neurotrauma, 2020-08, Vol.37 (15), p.1708-1719</ispartof><rights>Copyright Mary Ann Liebert, Inc. Aug 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c321t-36f3f660143aea6a498c1c0d77d8dabce817f3e9d338da70e4429af919fd55973</citedby><cites>FETCH-LOGICAL-c321t-36f3f660143aea6a498c1c0d77d8dabce817f3e9d338da70e4429af919fd55973</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32212901$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bighinati, Andrea</creatorcontrib><creatorcontrib>Focarete, Maria Letizia</creatorcontrib><creatorcontrib>Gualandi, Chiara</creatorcontrib><creatorcontrib>Pannella, Micaela</creatorcontrib><creatorcontrib>Giuliani, Alessandro</creatorcontrib><creatorcontrib>Beggiato, Sarah</creatorcontrib><creatorcontrib>Ferraro, Luca</creatorcontrib><creatorcontrib>Lorenzini, Luca</creatorcontrib><creatorcontrib>Giardino, Luciana</creatorcontrib><creatorcontrib>Calzà, Laura</creatorcontrib><title>Improved Functional Recovery in Rat Spinal Cord Injury Induced by a Drug Combination Administered with an Implantable Polymeric Delivery System</title><title>Journal of neurotrauma</title><addtitle>J Neurotrauma</addtitle><description>Spinal cord injury (SCI) is an incurable condition, in which a cascade of cellular and molecular events triggered by inflammation and excitotoxicity impairs endogenous regeneration, namely remyelination and axonal outgrowth. We designed a treatment solution based on an implantable biomaterial (electrospun poly (l-lactic acid) [PLLA]) loaded with ibuprofen and triiodothyronine (T3) to counteract inflammation, thus improving endogenous regeneration.
efficacy was tested by implanting the drug-loaded PLLA in the rat model of T8 contusion SCI. We observed the expected recovery of locomotion beginning on day 7. In PLLA-implanted rats (i.e., controls), the recovery stabilized at 21 days post-lesion (DPL), after which no further improvement was observed. On the contrary, in PLLA + ibuprofen (Ibu) + T3 (PLLA-Ibu-T3) rats a further recovery and a significant treatment effect were observed, also confirmed by the gait analysis on 49 DPL. Glutamate release at 24 h and 8 DPL was reduced in PLLA-Ibu-T3- compared to PLLA-implanted rats, such as the estimated lesion volume at 60 DPL. The myelin- and 200-neurofilament-positive area fraction was higher in PLLA-Ibu-T3-implanted rats, where the percentage of astrocytes was significantly reduced. The implant of a PLLA electrospun scaffold loaded with Ibu and T3 significantly improves the endogenous regeneration, leading to an improvement of functional locomotion outcome in the SCI.</description><subject>Astrocytes</subject><subject>Biomaterials</subject><subject>Contusions</subject><subject>Excitotoxicity</subject><subject>Gait</subject><subject>Gamma rays</subject><subject>Ibuprofen</subject><subject>Inflammation</subject><subject>Laboratory animals</subject><subject>Locomotion</subject><subject>Medical research</subject><subject>Myelin</subject><subject>Myelination</subject><subject>Neurodegeneration</subject><subject>Nonsteroidal anti-inflammatory drugs</subject><subject>Polylactic acid</subject><subject>Recovery of function</subject><subject>Regeneration</subject><subject>Spinal cord injuries</subject><subject>Thyroid hormones</subject><subject>Transplants & implants</subject><subject>Trauma</subject><subject>Triiodothyronine</subject><issn>0897-7151</issn><issn>1557-9042</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNpdkU9v1DAQxS0EokvLkSuyxKWXLP6TxPGx2tKyUiVQW86RY0_Aq8RZ7BiUT9Gv3AktHDhZM-_nN_Y8Qt5xtuWs0R8D5K1gXG9rXeoXZMOrShWaleIl2aCuCsUrfkLepHRgjMtaqNfkRArBhWZ8Qx724zFOv8DRqxzs7KdgBnoLFltxoT7QWzPTu6Nf27spOroPh4zKPrhs8Va3UEMvY_6O6tghtlrQCzf64NMMEZHffv5BTaA4aTBhNt0A9Os0LCNEb-klDP7PrLsF-fGMvOrNkODt83lKvl19ut99Lm6-XO93FzeFlYLPhax72dc146U0YGpT6sZyy5xSrnGms9Bw1UvQTkqsFYOyFNr0muveVZVW8pScP_ni739mSHM7-mRhwBfClFMrZFNyrRlrEP3wH3qYcsSFIIWujdKcaaSKJ8rGKaUIfXuMfjRxaTlr16RaTKpdk2rXpJB__-yauxHcP_pvNPIR46OQYw</recordid><startdate>20200801</startdate><enddate>20200801</enddate><creator>Bighinati, Andrea</creator><creator>Focarete, Maria Letizia</creator><creator>Gualandi, Chiara</creator><creator>Pannella, Micaela</creator><creator>Giuliani, Alessandro</creator><creator>Beggiato, Sarah</creator><creator>Ferraro, Luca</creator><creator>Lorenzini, Luca</creator><creator>Giardino, Luciana</creator><creator>Calzà, Laura</creator><general>Mary Ann Liebert, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20200801</creationdate><title>Improved Functional Recovery in Rat Spinal Cord Injury Induced by a Drug Combination Administered with an Implantable Polymeric Delivery System</title><author>Bighinati, Andrea ; Focarete, Maria Letizia ; Gualandi, Chiara ; Pannella, Micaela ; Giuliani, Alessandro ; Beggiato, Sarah ; Ferraro, Luca ; Lorenzini, Luca ; Giardino, Luciana ; Calzà, Laura</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c321t-36f3f660143aea6a498c1c0d77d8dabce817f3e9d338da70e4429af919fd55973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Astrocytes</topic><topic>Biomaterials</topic><topic>Contusions</topic><topic>Excitotoxicity</topic><topic>Gait</topic><topic>Gamma rays</topic><topic>Ibuprofen</topic><topic>Inflammation</topic><topic>Laboratory animals</topic><topic>Locomotion</topic><topic>Medical research</topic><topic>Myelin</topic><topic>Myelination</topic><topic>Neurodegeneration</topic><topic>Nonsteroidal anti-inflammatory drugs</topic><topic>Polylactic acid</topic><topic>Recovery of function</topic><topic>Regeneration</topic><topic>Spinal cord injuries</topic><topic>Thyroid hormones</topic><topic>Transplants & implants</topic><topic>Trauma</topic><topic>Triiodothyronine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bighinati, Andrea</creatorcontrib><creatorcontrib>Focarete, Maria Letizia</creatorcontrib><creatorcontrib>Gualandi, Chiara</creatorcontrib><creatorcontrib>Pannella, Micaela</creatorcontrib><creatorcontrib>Giuliani, Alessandro</creatorcontrib><creatorcontrib>Beggiato, Sarah</creatorcontrib><creatorcontrib>Ferraro, Luca</creatorcontrib><creatorcontrib>Lorenzini, Luca</creatorcontrib><creatorcontrib>Giardino, Luciana</creatorcontrib><creatorcontrib>Calzà, Laura</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurotrauma</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bighinati, Andrea</au><au>Focarete, Maria Letizia</au><au>Gualandi, Chiara</au><au>Pannella, Micaela</au><au>Giuliani, Alessandro</au><au>Beggiato, Sarah</au><au>Ferraro, Luca</au><au>Lorenzini, Luca</au><au>Giardino, Luciana</au><au>Calzà, Laura</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improved Functional Recovery in Rat Spinal Cord Injury Induced by a Drug Combination Administered with an Implantable Polymeric Delivery System</atitle><jtitle>Journal of neurotrauma</jtitle><addtitle>J Neurotrauma</addtitle><date>2020-08-01</date><risdate>2020</risdate><volume>37</volume><issue>15</issue><spage>1708</spage><epage>1719</epage><pages>1708-1719</pages><issn>0897-7151</issn><eissn>1557-9042</eissn><abstract>Spinal cord injury (SCI) is an incurable condition, in which a cascade of cellular and molecular events triggered by inflammation and excitotoxicity impairs endogenous regeneration, namely remyelination and axonal outgrowth. We designed a treatment solution based on an implantable biomaterial (electrospun poly (l-lactic acid) [PLLA]) loaded with ibuprofen and triiodothyronine (T3) to counteract inflammation, thus improving endogenous regeneration.
efficacy was tested by implanting the drug-loaded PLLA in the rat model of T8 contusion SCI. We observed the expected recovery of locomotion beginning on day 7. In PLLA-implanted rats (i.e., controls), the recovery stabilized at 21 days post-lesion (DPL), after which no further improvement was observed. On the contrary, in PLLA + ibuprofen (Ibu) + T3 (PLLA-Ibu-T3) rats a further recovery and a significant treatment effect were observed, also confirmed by the gait analysis on 49 DPL. Glutamate release at 24 h and 8 DPL was reduced in PLLA-Ibu-T3- compared to PLLA-implanted rats, such as the estimated lesion volume at 60 DPL. The myelin- and 200-neurofilament-positive area fraction was higher in PLLA-Ibu-T3-implanted rats, where the percentage of astrocytes was significantly reduced. The implant of a PLLA electrospun scaffold loaded with Ibu and T3 significantly improves the endogenous regeneration, leading to an improvement of functional locomotion outcome in the SCI.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>32212901</pmid><doi>10.1089/neu.2019.6949</doi><tpages>12</tpages></addata></record> |
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| subjects | Astrocytes Biomaterials Contusions Excitotoxicity Gait Gamma rays Ibuprofen Inflammation Laboratory animals Locomotion Medical research Myelin Myelination Neurodegeneration Nonsteroidal anti-inflammatory drugs Polylactic acid Recovery of function Regeneration Spinal cord injuries Thyroid hormones Transplants & implants Trauma Triiodothyronine |
| title | Improved Functional Recovery in Rat Spinal Cord Injury Induced by a Drug Combination Administered with an Implantable Polymeric Delivery System |
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