The R18 Polyarginine Peptide Is More Effective Than the TAT-NR2B9c (NA-1) Peptide When Administered 60 Minutes after Permanent Middle Cerebral Artery Occlusion in the Rat
We examined the dose responsiveness of polyarginine R18 (100, 300, and 1000 nmol/kg) when administered 60 minutes after permanent middle cerebral artery occlusion (MCAO). The TAT-NR2B9c peptide, which is known to be neuroprotective in rodent and nonhuman primate stroke models, served as a positive c...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2016-01-01
|
| Series: | Stroke Research and Treatment |
| Online Access: | http://dx.doi.org/10.1155/2016/2372710 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832559935561400320 |
|---|---|
| author | D. Milani N. W. Knuckey R. S. Anderton J. L. Cross B. P. Meloni |
| author_facet | D. Milani N. W. Knuckey R. S. Anderton J. L. Cross B. P. Meloni |
| author_sort | D. Milani |
| collection | DOAJ |
| description | We examined the dose responsiveness of polyarginine R18 (100, 300, and 1000 nmol/kg) when administered 60 minutes after permanent middle cerebral artery occlusion (MCAO). The TAT-NR2B9c peptide, which is known to be neuroprotective in rodent and nonhuman primate stroke models, served as a positive control. At 24 hours after MCAO, there was reduced total infarct volume in R18 treated animals at all doses, but this reduction only reached statistical significance at doses of 100 and 1000 nmol/kg. The TAT-NR2B9c peptide reduced infarct volume at doses of 300 and 1000 nmol/kg, but not to a statistically significant extent, while the 100 nmol/kg dose was ineffective. The reduction in infarct volume with R18 and TAT-NR2B9c peptide treatments was mirrored by improvements in one or more functional outcomes (namely, neurological score, adhesive tape removal, and rota-rod), but not to a statistically significant extent. These findings further confirm the neuroprotective properties of polyarginine peptides and for R18 extend its therapeutic time window and dose range, as well as demonstrating its greater efficacy compared to TAT-NR2B9c in a severe stroke model. The superior neuroprotective efficacy of R18 over TAT-NR2B9c highlights the potential of this polyarginine peptide as a lead candidate for studies in human stroke. |
| format | Article |
| id | doaj-art-d94f26b0af134d359f6bb04e58e3ade0 |
| institution | Kabale University |
| issn | 2090-8105 2042-0056 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stroke Research and Treatment |
| spelling | doaj-art-d94f26b0af134d359f6bb04e58e3ade02025-02-03T01:28:56ZengWileyStroke Research and Treatment2090-81052042-00562016-01-01201610.1155/2016/23727102372710The R18 Polyarginine Peptide Is More Effective Than the TAT-NR2B9c (NA-1) Peptide When Administered 60 Minutes after Permanent Middle Cerebral Artery Occlusion in the RatD. Milani0N. W. Knuckey1R. S. Anderton2J. L. Cross3B. P. Meloni4School of Health Sciences, The University of Notre Dame Australia, Fremantle, WA 6160, AustraliaWestern Australian Neuroscience Research Institute, Nedlands, WA 6009, AustraliaSchool of Health Sciences, The University of Notre Dame Australia, Fremantle, WA 6160, AustraliaWestern Australian Neuroscience Research Institute, Nedlands, WA 6009, AustraliaWestern Australian Neuroscience Research Institute, Nedlands, WA 6009, AustraliaWe examined the dose responsiveness of polyarginine R18 (100, 300, and 1000 nmol/kg) when administered 60 minutes after permanent middle cerebral artery occlusion (MCAO). The TAT-NR2B9c peptide, which is known to be neuroprotective in rodent and nonhuman primate stroke models, served as a positive control. At 24 hours after MCAO, there was reduced total infarct volume in R18 treated animals at all doses, but this reduction only reached statistical significance at doses of 100 and 1000 nmol/kg. The TAT-NR2B9c peptide reduced infarct volume at doses of 300 and 1000 nmol/kg, but not to a statistically significant extent, while the 100 nmol/kg dose was ineffective. The reduction in infarct volume with R18 and TAT-NR2B9c peptide treatments was mirrored by improvements in one or more functional outcomes (namely, neurological score, adhesive tape removal, and rota-rod), but not to a statistically significant extent. These findings further confirm the neuroprotective properties of polyarginine peptides and for R18 extend its therapeutic time window and dose range, as well as demonstrating its greater efficacy compared to TAT-NR2B9c in a severe stroke model. The superior neuroprotective efficacy of R18 over TAT-NR2B9c highlights the potential of this polyarginine peptide as a lead candidate for studies in human stroke.http://dx.doi.org/10.1155/2016/2372710 |
| spellingShingle | D. Milani N. W. Knuckey R. S. Anderton J. L. Cross B. P. Meloni The R18 Polyarginine Peptide Is More Effective Than the TAT-NR2B9c (NA-1) Peptide When Administered 60 Minutes after Permanent Middle Cerebral Artery Occlusion in the Rat Stroke Research and Treatment |
| title | The R18 Polyarginine Peptide Is More Effective Than the TAT-NR2B9c (NA-1) Peptide When Administered 60 Minutes after Permanent Middle Cerebral Artery Occlusion in the Rat |
| title_full | The R18 Polyarginine Peptide Is More Effective Than the TAT-NR2B9c (NA-1) Peptide When Administered 60 Minutes after Permanent Middle Cerebral Artery Occlusion in the Rat |
| title_fullStr | The R18 Polyarginine Peptide Is More Effective Than the TAT-NR2B9c (NA-1) Peptide When Administered 60 Minutes after Permanent Middle Cerebral Artery Occlusion in the Rat |
| title_full_unstemmed | The R18 Polyarginine Peptide Is More Effective Than the TAT-NR2B9c (NA-1) Peptide When Administered 60 Minutes after Permanent Middle Cerebral Artery Occlusion in the Rat |
| title_short | The R18 Polyarginine Peptide Is More Effective Than the TAT-NR2B9c (NA-1) Peptide When Administered 60 Minutes after Permanent Middle Cerebral Artery Occlusion in the Rat |
| title_sort | r18 polyarginine peptide is more effective than the tat nr2b9c na 1 peptide when administered 60 minutes after permanent middle cerebral artery occlusion in the rat |
| url | http://dx.doi.org/10.1155/2016/2372710 |
| work_keys_str_mv | AT dmilani ther18polyargininepeptideismoreeffectivethanthetatnr2b9cna1peptidewhenadministered60minutesafterpermanentmiddlecerebralarteryocclusionintherat AT nwknuckey ther18polyargininepeptideismoreeffectivethanthetatnr2b9cna1peptidewhenadministered60minutesafterpermanentmiddlecerebralarteryocclusionintherat AT rsanderton ther18polyargininepeptideismoreeffectivethanthetatnr2b9cna1peptidewhenadministered60minutesafterpermanentmiddlecerebralarteryocclusionintherat AT jlcross ther18polyargininepeptideismoreeffectivethanthetatnr2b9cna1peptidewhenadministered60minutesafterpermanentmiddlecerebralarteryocclusionintherat AT bpmeloni ther18polyargininepeptideismoreeffectivethanthetatnr2b9cna1peptidewhenadministered60minutesafterpermanentmiddlecerebralarteryocclusionintherat AT dmilani r18polyargininepeptideismoreeffectivethanthetatnr2b9cna1peptidewhenadministered60minutesafterpermanentmiddlecerebralarteryocclusionintherat AT nwknuckey r18polyargininepeptideismoreeffectivethanthetatnr2b9cna1peptidewhenadministered60minutesafterpermanentmiddlecerebralarteryocclusionintherat AT rsanderton r18polyargininepeptideismoreeffectivethanthetatnr2b9cna1peptidewhenadministered60minutesafterpermanentmiddlecerebralarteryocclusionintherat AT jlcross r18polyargininepeptideismoreeffectivethanthetatnr2b9cna1peptidewhenadministered60minutesafterpermanentmiddlecerebralarteryocclusionintherat AT bpmeloni r18polyargininepeptideismoreeffectivethanthetatnr2b9cna1peptidewhenadministered60minutesafterpermanentmiddlecerebralarteryocclusionintherat |