Asadullah, - and Abdul Hafid Bajamal, - and Muhammad Arifin Parenrengi, - and Agus Turchan, Agus and Budi Utomo, - and I Ketut Sudiana, - and Eko Agus Subagio, Eko (2023) 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). F1000Research, 12. pp. 1-13. ISSN 2046-1402

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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, ACTH4 19Pro8-Gly9-Pro!9 (ACTH4. 19) also known as semax, has shown neuroprotective and anti-inflammatory properties. ACTH4 19 has also been actively used in the treatment of brain ischemia without serious complication reported. Here, we analyzed the effects of ACTH, 19 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 atthe 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. ACTH4 19 was administered intranasally to the treatment group and 0.996 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. Guantitative measurement of the cytokines was done in the posterior horn area with specific associated antimonoclonal antibodies. Results: Rats with mild SCI that were given ACTH4 19 showed greater anti-inflammatory levels at 3 hours post-compression but only IL-10 and IL-13 were elevated significantiy at 6 hours. Rats with severe compression in ACTH4 19 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 ACTH4 19Pro8-Gly9-Pro!? 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.

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