Characterisation of Peptide5 systemic administration for treating traumatic spinal cord injured rats
Systemic administration of a Connexin43 mimetic peptide, Peptide5, has been shown to reduce secondary tissue damage and improve functional recovery after spinal cord injury (SCI). This study investigated safety measures and potential off-target effects of Peptide5 systemic administration. Rats were...
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| Veröffentlicht in: | Experimental brain research 2017-10, Vol.235 (10), p.3033-3048 |
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| creator | Mao, Yilin Nguyen, Tara Tonkin, Ryan S. Lees, Justin G. Warren, Caitlyn O’Carroll, Simon J. Nicholson, Louise F. B. Green, Colin R. Moalem-Taylor, Gila Gorrie, Catherine A. |
| description | Systemic administration of a Connexin43 mimetic peptide, Peptide5, has been shown to reduce secondary tissue damage and improve functional recovery after spinal cord injury (SCI). This study investigated safety measures and potential off-target effects of Peptide5 systemic administration. Rats were subjected to a mild contusion SCI using the New York University impactor. One cohort was injected intraperitoneally with a single dose of fluorescently labelled Peptide5 and euthanised at 2 or 4 h post-injury for peptide distribution analysis. A second cohort received intraperitoneal injections of Peptide5 or a scrambled peptide and was culled at 8 or 24 h post-injury for the analysis of connexin proteins and systemic cytokine profile. We found that Peptide5 did not cross the blood-spinal cord barrier in control animals, but reached the lesion area in the spinal cord-injured animals without entering non-injured tissue. There was no evidence that the systemic administration of Peptide5 modulates Connexin43 protein expression or hemichannel closure in the heart and lung tissue of SCI animals. The expression levels of other major connexin proteins including Connexin30 in astrocytes, Connexin36 in neurons and Connexin47 in oligodendrocytes were also unaltered by systemic delivery of Peptide5 in either the injured or non-injured spinal cords. In addition, systemic delivery of Peptide5 had no significant effect on the plasma levels of cytokines, chemokines or growth factors. These data indicate that the systemic delivery of Peptide5 is unlikely to cause any off-target or adverse effects and may thus be a safe treatment option for traumatic SCI. |
| doi_str_mv | 10.1007/s00221-017-5023-3 |
| format | Article |
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B. ; Green, Colin R. ; Moalem-Taylor, Gila ; Gorrie, Catherine A.</creator><creatorcontrib>Mao, Yilin ; Nguyen, Tara ; Tonkin, Ryan S. ; Lees, Justin G. ; Warren, Caitlyn ; O’Carroll, Simon J. ; Nicholson, Louise F. B. ; Green, Colin R. ; Moalem-Taylor, Gila ; Gorrie, Catherine A.</creatorcontrib><description>Systemic administration of a Connexin43 mimetic peptide, Peptide5, has been shown to reduce secondary tissue damage and improve functional recovery after spinal cord injury (SCI). This study investigated safety measures and potential off-target effects of Peptide5 systemic administration. Rats were subjected to a mild contusion SCI using the New York University impactor. One cohort was injected intraperitoneally with a single dose of fluorescently labelled Peptide5 and euthanised at 2 or 4 h post-injury for peptide distribution analysis. A second cohort received intraperitoneal injections of Peptide5 or a scrambled peptide and was culled at 8 or 24 h post-injury for the analysis of connexin proteins and systemic cytokine profile. We found that Peptide5 did not cross the blood-spinal cord barrier in control animals, but reached the lesion area in the spinal cord-injured animals without entering non-injured tissue. There was no evidence that the systemic administration of Peptide5 modulates Connexin43 protein expression or hemichannel closure in the heart and lung tissue of SCI animals. The expression levels of other major connexin proteins including Connexin30 in astrocytes, Connexin36 in neurons and Connexin47 in oligodendrocytes were also unaltered by systemic delivery of Peptide5 in either the injured or non-injured spinal cords. In addition, systemic delivery of Peptide5 had no significant effect on the plasma levels of cytokines, chemokines or growth factors. These data indicate that the systemic delivery of Peptide5 is unlikely to cause any off-target or adverse effects and may thus be a safe treatment option for traumatic SCI.</description><identifier>ISSN: 0014-4819</identifier><identifier>EISSN: 1432-1106</identifier><identifier>DOI: 10.1007/s00221-017-5023-3</identifier><identifier>PMID: 28725925</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Animals ; Astrocytes ; Biomedical and Life Sciences ; Biomedicine ; Care and treatment ; Chemokines ; Connexin 43 ; Connexins ; Cytokines ; Growth factors ; Health aspects ; Injury analysis ; Neurology ; Neurosciences ; Oligodendrocytes ; Peptides ; Physiological aspects ; Plasma levels ; Rats ; Recovery of function ; Research Article ; Rodents ; Safety measures ; Spinal cord ; Spinal cord injuries</subject><ispartof>Experimental brain research, 2017-10, Vol.235 (10), p.3033-3048</ispartof><rights>Springer-Verlag GmbH Germany 2017</rights><rights>COPYRIGHT 2017 Springer</rights><rights>Experimental Brain Research is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c573t-287f82831c44d7e473edcb3b207583eafd95bd631a6a831e51043a07d58380c73</citedby><cites>FETCH-LOGICAL-c573t-287f82831c44d7e473edcb3b207583eafd95bd631a6a831e51043a07d58380c73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00221-017-5023-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00221-017-5023-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28725925$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mao, Yilin</creatorcontrib><creatorcontrib>Nguyen, Tara</creatorcontrib><creatorcontrib>Tonkin, Ryan S.</creatorcontrib><creatorcontrib>Lees, Justin G.</creatorcontrib><creatorcontrib>Warren, Caitlyn</creatorcontrib><creatorcontrib>O’Carroll, Simon J.</creatorcontrib><creatorcontrib>Nicholson, Louise F. B.</creatorcontrib><creatorcontrib>Green, Colin R.</creatorcontrib><creatorcontrib>Moalem-Taylor, Gila</creatorcontrib><creatorcontrib>Gorrie, Catherine A.</creatorcontrib><title>Characterisation of Peptide5 systemic administration for treating traumatic spinal cord injured rats</title><title>Experimental brain research</title><addtitle>Exp Brain Res</addtitle><addtitle>Exp Brain Res</addtitle><description>Systemic administration of a Connexin43 mimetic peptide, Peptide5, has been shown to reduce secondary tissue damage and improve functional recovery after spinal cord injury (SCI). This study investigated safety measures and potential off-target effects of Peptide5 systemic administration. Rats were subjected to a mild contusion SCI using the New York University impactor. One cohort was injected intraperitoneally with a single dose of fluorescently labelled Peptide5 and euthanised at 2 or 4 h post-injury for peptide distribution analysis. A second cohort received intraperitoneal injections of Peptide5 or a scrambled peptide and was culled at 8 or 24 h post-injury for the analysis of connexin proteins and systemic cytokine profile. We found that Peptide5 did not cross the blood-spinal cord barrier in control animals, but reached the lesion area in the spinal cord-injured animals without entering non-injured tissue. There was no evidence that the systemic administration of Peptide5 modulates Connexin43 protein expression or hemichannel closure in the heart and lung tissue of SCI animals. The expression levels of other major connexin proteins including Connexin30 in astrocytes, Connexin36 in neurons and Connexin47 in oligodendrocytes were also unaltered by systemic delivery of Peptide5 in either the injured or non-injured spinal cords. In addition, systemic delivery of Peptide5 had no significant effect on the plasma levels of cytokines, chemokines or growth factors. These data indicate that the systemic delivery of Peptide5 is unlikely to cause any off-target or adverse effects and may thus be a safe treatment option for traumatic SCI.</description><subject>Animals</subject><subject>Astrocytes</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Care and treatment</subject><subject>Chemokines</subject><subject>Connexin 43</subject><subject>Connexins</subject><subject>Cytokines</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>Injury analysis</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Oligodendrocytes</subject><subject>Peptides</subject><subject>Physiological aspects</subject><subject>Plasma levels</subject><subject>Rats</subject><subject>Recovery of function</subject><subject>Research Article</subject><subject>Rodents</subject><subject>Safety measures</subject><subject>Spinal cord</subject><subject>Spinal cord injuries</subject><issn>0014-4819</issn><issn>1432-1106</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNp1kk2LFDEQhoMo7rj6A7xIgyB66LWSdDqZ4zL4sbCg-HEOmaR6JkN3Z0zSsPvvTdOr7oiSQ6pSTxVVlZeQ5xQuKIB8mwAYozVQWQtgvOYPyIo2nNWUQvuQrABoUzeKrs_Ik5QOs8slPCZnTEkm1kysiNvsTTQ2Y_TJZB_GKnTVZzxm71BU6TZlHLytjBv86FOOC9OFWOWIxRl3xTDTUExbpaMfTV_ZEF3lx8MU0VUlIz0ljzrTJ3x2d5-T7-_ffdt8rK8_fbjaXF7XVkie69JVp5ji1DaNk9hIjs5u-ZaBFIqj6dxabF3LqWlNoVBQaLgB6UpUgZX8nLxe6h5j-DFhynrwyWLfmxHDlDRdM0qZggYK-vIv9BCmWLqfqaYsVyngf6id6VH7sQtlWDsX1ZcCBG9lq0ShLv5BlePm3YURO1_eTxLenCQUJuNN3pkpJX319csp--oeu0fT530K_TT_QzoF6QLaGFKK2Olj9IOJt5qCnuWiF7noIhc9y0XP872428K0HdD9zviljwKwBUglNO4w3lvTf6v-BMJkxwM</recordid><startdate>20171001</startdate><enddate>20171001</enddate><creator>Mao, Yilin</creator><creator>Nguyen, Tara</creator><creator>Tonkin, Ryan S.</creator><creator>Lees, Justin G.</creator><creator>Warren, Caitlyn</creator><creator>O’Carroll, Simon J.</creator><creator>Nicholson, Louise F. B.</creator><creator>Green, Colin R.</creator><creator>Moalem-Taylor, Gila</creator><creator>Gorrie, Catherine A.</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>0-V</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7RV</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>88J</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ALSLI</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</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>M2R</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20171001</creationdate><title>Characterisation of Peptide5 systemic administration for treating traumatic spinal cord injured rats</title><author>Mao, Yilin ; Nguyen, Tara ; Tonkin, Ryan S. ; Lees, Justin G. ; Warren, Caitlyn ; O’Carroll, Simon J. ; Nicholson, Louise F. 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B.</au><au>Green, Colin R.</au><au>Moalem-Taylor, Gila</au><au>Gorrie, Catherine A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterisation of Peptide5 systemic administration for treating traumatic spinal cord injured rats</atitle><jtitle>Experimental brain research</jtitle><stitle>Exp Brain Res</stitle><addtitle>Exp Brain Res</addtitle><date>2017-10-01</date><risdate>2017</risdate><volume>235</volume><issue>10</issue><spage>3033</spage><epage>3048</epage><pages>3033-3048</pages><issn>0014-4819</issn><eissn>1432-1106</eissn><abstract>Systemic administration of a Connexin43 mimetic peptide, Peptide5, has been shown to reduce secondary tissue damage and improve functional recovery after spinal cord injury (SCI). This study investigated safety measures and potential off-target effects of Peptide5 systemic administration. Rats were subjected to a mild contusion SCI using the New York University impactor. One cohort was injected intraperitoneally with a single dose of fluorescently labelled Peptide5 and euthanised at 2 or 4 h post-injury for peptide distribution analysis. A second cohort received intraperitoneal injections of Peptide5 or a scrambled peptide and was culled at 8 or 24 h post-injury for the analysis of connexin proteins and systemic cytokine profile. We found that Peptide5 did not cross the blood-spinal cord barrier in control animals, but reached the lesion area in the spinal cord-injured animals without entering non-injured tissue. There was no evidence that the systemic administration of Peptide5 modulates Connexin43 protein expression or hemichannel closure in the heart and lung tissue of SCI animals. The expression levels of other major connexin proteins including Connexin30 in astrocytes, Connexin36 in neurons and Connexin47 in oligodendrocytes were also unaltered by systemic delivery of Peptide5 in either the injured or non-injured spinal cords. In addition, systemic delivery of Peptide5 had no significant effect on the plasma levels of cytokines, chemokines or growth factors. These data indicate that the systemic delivery of Peptide5 is unlikely to cause any off-target or adverse effects and may thus be a safe treatment option for traumatic SCI.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>28725925</pmid><doi>10.1007/s00221-017-5023-3</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Astrocytes Biomedical and Life Sciences Biomedicine Care and treatment Chemokines Connexin 43 Connexins Cytokines Growth factors Health aspects Injury analysis Neurology Neurosciences Oligodendrocytes Peptides Physiological aspects Plasma levels Rats Recovery of function Research Article Rodents Safety measures Spinal cord Spinal cord injuries |
| title | Characterisation of Peptide5 systemic administration for treating traumatic spinal cord injured rats |
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