CB1 cannabinoid receptor agonist inhibits matrix metalloproteinase activity in spinal cord injury: A possible mechanism of improved recovery.
| dc.contributor.author | Hong, Jun | |
| dc.contributor.author | Nandiwada, Vijaya | |
| dc.contributor.author | Jones, Victoria | |
| dc.contributor.author | Lu, Miaomiao | |
| dc.contributor.author | Warner, David S | |
| dc.contributor.author | Mukhopadhyay, Somnath | |
| dc.contributor.author | Sheng, Huaxin | |
| dc.date.accessioned | 2021-06-01T14:02:58Z | |
| dc.date.available | 2021-06-01T14:02:58Z | |
| dc.date.issued | 2015-06 | |
| dc.date.updated | 2021-06-01T14:02:57Z | |
| dc.description.abstract | Increased matrix metalloproteinase (MMP) activity contributes to glial scar formation that inhibits the repair path after spinal cord injury (SCI). We examined whether treatment with N-(2-chloroethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (ACEA), a selective synthetic cannabinoid receptor (CB1R) agonist, inhibits MMP and improves functional and histological recovery in a mouse spinal cord compression injury model. Injured mice randomly received either intraperitoneal ACEA (3mg/kg/day) or vehicle for up to 3 weeks. Behavioral, histological and biochemical assays were performed. Rotarod assessment and the Basso Mouse Scale score showed an improved performance following ACEA treatment concomitant with a decrease in compression lesion volume. MMP-9 and MMP-2 activity was measured at 1, 7 and 14 days post-SCI. SCI markedly increased MMP-9, but had negligible effect on MMP-2 activity. ACEA-treatment decreased MMP-9 activity by 80%, 49%, and 56%, respectively (P<0.05) and had a smaller effect on MMP-2 activity. The CB1R antagonist SR141716, but not the CB2R antagonist SR144528, blocked ACEA-mediated decrease in MMP-9 activity confirming the role of the CB1R in the process. Collectively these data demonstrate that post-injury CB1R agonism can improve SCI outcome and also indicate marked attenuation of MMP-9 proteolytic enzyme activity as a biochemical mechanism. | |
| dc.identifier | S0304-3940(15)00297-9 | |
| dc.identifier.issn | 0304-3940 | |
| dc.identifier.issn | 1872-7972 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Elsevier BV | |
| dc.relation.ispartof | Neuroscience letters | |
| dc.relation.isversionof | 10.1016/j.neulet.2015.04.016 | |
| dc.subject | Spinal Cord | |
| dc.subject | Animals | |
| dc.subject | Mice, Inbred C57BL | |
| dc.subject | Spinal Cord Injuries | |
| dc.subject | Arachidonic Acids | |
| dc.subject | Receptor, Cannabinoid, CB1 | |
| dc.subject | Receptor, Cannabinoid, CB2 | |
| dc.subject | Male | |
| dc.subject | Matrix Metalloproteinase 9 | |
| dc.subject | Matrix Metalloproteinase Inhibitors | |
| dc.title | CB1 cannabinoid receptor agonist inhibits matrix metalloproteinase activity in spinal cord injury: A possible mechanism of improved recovery. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Sheng, Huaxin|0000-0002-4325-2940 | |
| pubs.begin-page | 19 | |
| pubs.end-page | 24 | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Neurobiology | |
| pubs.organisational-group | Duke Institute for Brain Sciences | |
| pubs.organisational-group | Surgery | |
| pubs.organisational-group | Anesthesiology, Neuroanesthesia | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Basic Science Departments | |
| pubs.organisational-group | University Institutes and Centers | |
| pubs.organisational-group | Institutes and Provost's Academic Units | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Anesthesiology | |
| pubs.publication-status | Published | |
| pubs.volume | 597 |