Effect of ACTH4-10Pro8-Gly9-Pro10 on anti-inflammatory cytokine (IL-4, IL-10, IL-13) expression in acute spinal cord injury models (male Sprague Dawley rats)
ACTH4-10 (Semax) appears to increase anti-inflammatory cytokine levels in rat models of spinal cord injury, but further research is needed to evaluate its clinical relevance.
Where it sits
this study against the rest of the semax corpusSummary and findings
This study investigated the effects of ACTH4-10 (Semax) on anti-inflammatory cytokine expression in male Sprague Dawley rats following acute spinal cord injury (SCI). The treatment group received intranasal ACTH4-10, while the control group received a placebo. Results indicated increased levels of IL-10 and IL-13 in the treatment group at various time points post-injury.
Abstract
Background Spinal cord injury (SCI) is a damage to the spinal cord caused mainly by trauma resulting in major motor, sensory and autonomic dysfunctions. Its final neurological outcome is determined by both primary and secondary injury processes. A key component of secondary injury mechanisms after initial trauma is neuroinflammation. A neuroprotective compound, ACTH 4-10 Pro 8 -Gly 9 -Pro 10 (ACTH 4-10 ) also known as semax, has shown neuroprotective and anti-inflammatory properties. ACTH 4-10 has also been actively used in the treatment of brain ischemia without serious complication reported. Here, we analyzed the effects of ACTH 4-10 at regulating the inflammatory cascade in SCI by looking at anti-inflammatory cytokine (IL-4, IL-10 and IL-13) levels after acute SCI. Method We carried out laminectomies in male Sprague Dawley rats at the second thoracic vertebrae. After laminectomy, we exposed the myelum and created mild SCI models with 20-g, and severe SCI with 35-g aneurysm clips. ACTH 4-10 was administered intranasally to the treatment group and 0.9% NaCl to the control group (placebo). Both groups were kept alive and terminated at 3 and 6 hours. The tissue sample preparations were fixed in formalin and examined for immunohistochemistry. Quantitative measurement of the cytokines was done in the posterior horn area with specific associated anti-monoclonal antibodies. Results Rats with mild SCI that were given ACTH 4-10 showed greater anti-inflammatory levels at 3 hours post-compression but only IL-10 and IL-13 were elevated significantly at 6 hours. Rats with severe compression in ACTH 4-10 group showed greater levels of IL-10, IL-13 at 3 hours and IL-4, IL-10 at 6 hours compared with the placebo group. Conclusions Administration of ACTH 4-10 Pro 8 -Gly 9 -Pro 10 intranasal can increase anti-inflammatory cytokine expression in Sprague Dawley rat models with mild and severe SCI. Expression of anti-inflammatory cytokines was greater in mild compression and 3-hour termination. Further research is needed to determine the optimal dose and clinical outcome in vivo.