Meglumine cyclic adenylate improves neurological function following acute spinal cord injury in rats.

Abstract

Elevation of intracellular cyclic adenosine monophosphate (cAMP) levels facilitates recovery following spinal injury by suppressing secondary pathology and promoting axonal regeneration. However, this treatment strategy is limited by lack of effective and tolerable clinical agents. The present study examined the effects of meglumine cyclic adenylate (MCA) on neurological recovery, cAMP concentration, adenylate cyclase 3 (AC3) activity and phosphodiesterase 4D (PDE4D) activity during early stage acute spinal cord injury (SCI) in rats. A total of 48 Sprague‑Dawley rats were randomly assigned to groups A, B or C, each consisting of 16 animals. SCI was induced by Allen's method using a 7 g x 3 cm extradural weight‑drop impact on spinal cord segment T11. A total of 30 min following SCI, group A received a single 30 mg/kg‑bw i.p. dose of methylprednisolone, group B received 2 mg/kg‑bw i.p. MCA daily for seven days and group C were administered an equal volume of normal saline. Seven days following SCI, the spinal cord samples from eight rats per group were obtained to measure the cAMP concentration, and the activities of AC3 and PDE4D. The remaining eight rats per group were used for behavioral assessments using the inclined plane stability test and Gale scale for up to six weeks post‑SCI. The drug‑treated groups A and B had higher cAMP concentrations and AC3 activities but lower PDE4D activities at the lesion sites, as well as superior behavioral scores post‑SCI compared with the vehicle‑treated group C (P<0.05). Furthermore, cAMP was higher in group B than in group A (P<0.05). It was concluded that MCA may serve as an effective SCI treatment by activating AC3 and suppressing PDE4D.

• Authors: Jingwu Liao, Jingming Xie, Daqiang Lin, Ning Lu, Limin Guo, Weiqiang Li, Bo Pu, Yang Yang, Zhenlong Yang, Ying Zhang, Yueming Song
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 10 Issue 3 Pg. 1225-30 (Sep 2014) ISSN: 1791-3004 [Electronic] Greece
• PMID: 24970286 (Publication Type: Journal Article)

Chemical References

• meglumine cyclic adenylate
• Meglumine
• Cyclic AMP
• Cyclic Nucleotide Phosphodiesterases, Type 4
• PDE4D protein, rat
• Adenylyl Cyclases
• adenylate cyclase 3
• Methylprednisolone

Topics

• Adenylyl Cyclases (metabolism)
• Animals
• Behavior, Animal (drug effects)
• Cyclic AMP (analogs & derivatives, metabolism, pharmacology)
• Cyclic Nucleotide Phosphodiesterases, Type 4 (metabolism)
• Dose-Response Relationship, Drug
• Female
• Immunohistochemistry
• Male
• Meglumine (analogs & derivatives, pharmacology)
• Methylprednisolone (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Spinal Cord (drug effects, pathology)
• Spinal Cord Injuries (drug therapy, pathology)