meglumine-cyclic-adenylate and Spinal-Cord-Injuries

Animal experimental study.. Spinal cord injury (SCI) at or above the T6 level causes cardiovascular dysfunction. Maintaining cAMP levels with cAMP analogs can facilitate neurological recovery. In the present study, the effects of meglumine cyclic adenylate (MCA), a cAMP analog and approved cardiovascular drug, on cardiovascular and neurological recovery in acute T4-SCI in rats were investigated.. Hospital in Kunming, China.. Eighty rats were randomly allocated to five groups, and groups A-D received SCI: (A) a group administered MCA at 2 mg/kg/d iv qd, (B) a group administered dopamine at 2.5 to 5 μg/kg/min iv to maintain mean arterial pressure above 85 mm Hg, (C) a group administered atropine at 1 mg/kg iv bid, (D) a group receiving an equal volume of saline iv qd for 3 weeks after SCI and (E) a group undergoing laminectomy only. The cardiovascular and behavioral parameters of the rats were examined, and spinal cord tissues were processed for hematoxylin and eosin staining, Nissl staining, electron microscopy, and analysis of cAMP levels.. Compared with dopamine or atropine, MCA significantly reversed the decrease in cAMP levels in both myocardial cells and the injured spinal cord; improved hypotension, bradycardia and behavioral parameters at 6 weeks; and improved spinal cord blood flow and histological structure at 7 days post-SCI. The regression analysis suggested spinal cord motor-function improved as decreased heart rate and mean arterial pressure were stopped post-SCI.. MCA may be an effective treatment for acute SCI by sustaining cAMP-dependent reparative processes and improving post-SCI cardiovascular dysfunction.. N/A.

Topics: Animals; Atropine Derivatives; Disease Models, Animal; Dopamine; Hemodynamics; Rats; Recovery of Function; Spinal Cord; Spinal Cord Injuries

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.

Topics: Adenylyl Cyclases; Animals; Behavior, Animal; Cyclic AMP; Cyclic Nucleotide Phosphodiesterases, Type 4; Dose-Response Relationship, Drug; Female; Immunohistochemistry; Male; Meglumine; Methylprednisolone; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries