Protective effects of LM22A-4 on injured spinal cord nerves

Objective: The goal of this study was to elucidate the protection by and potential mechanisms of LM22A-4, a specific agonist of tyrosine kinase receptor B, against spinal cord injury (SCI).

Methods: Spinal cord trauma was induced by the application of vascular clips to the dura of mice via a four-level T7-T11 laminectomy. Thirty minutes after the injury, an abdominal injection of LM22A-4 (at dosages of 10 mg/kg and 15 mg/kg) or an equal volume of solvent was provided. Twenty-four hours after SCI, a Western blot was performed to examine the expression of p-TrkB, p-Akt, p-ERK, cleaved-caspase-3, and Bcl-2; a TUNEL assay and Nissl staining were performed to study Apoptosis and the survival of neurons. In addition, another batch of mice was allowed to live for 14 days after the SCI treatment, during which the LM22A-4 was provided at the same time each day and the neurological function was assessed.

Results: Spinal cord injury in mice resulted in severe trauma characterized by tissue damage and Apoptosis. Treatment of the mice with LM22A-4 (10 mg/kg) significantly reduced the degree of tissue injury (histological score) and Apoptosis (TUNEL staining and Caspase-3 and Bcl-2 expression) compared with vehicle treated group (P < 0.05). In a separate set of experiments, chronic treatment with LM22A-4 also significantly ameliorated the recovery of limb function (P < 0.05).

Conclusion: This study provides an experimental evidence that LM22A-4 reduces the development of tissue injury associated with spinal cord trauma, and activation of the activity of TrkB may represent a novel approach for the therapy of spinal cord trauma.