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Effects of ACTH4-10Pro8-Gly9-Pro10 on anti-inflammatory cytokine (IL-4, IL-10, IL-13) expression in acute spinal cord injury model (Sprague Dawley rats)

Asadullah, Asadullah1; Subagio, Eko Agus1; Bajamal, Abdul Hafid1; Parenrengi, Muhammad Arifin1; Turchan, Agus1

Research facility: Airlangga University
Published Dec 23, 2022; Updated Jan 25, 2023 on Dryad. https://doi.org/10.5061/dryad.76hdr7t12

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Dec 23, 2022 version files 6.74 MB
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Abstract

Background: Spinal cord injury (SCI) is a destructive neurological and pathological state that causes major motor, sensory and autonomic dysfunctions. It’s final neurological outcome determined from both primary and secondary injury process. Neuroinflammation is a key component of the secondary injury mechanisms with local and systemic consequences. A neuroprotective compound, ACTH4-10Pro8-Gly9-Pro10 also known as Semax has shown neuroprotective and anti-inflammatory properties. ACTH4-10Pro8-Gly9-Pro10 also has actively used in the treatment of brain ischemia without serious complication reported. Here we analyzed the effects of ACTH4-10Pro8-Gly9-Pro10 in regulating inflammatory cascade in SCI by looking at the expression of anti-inflammatory cytokine IL-4, IL-10, IL-13 in acute compression SCI.

Method: We do laminectomy in Sprague Dawley rats at the second thoracic vertebrae. After laminectomy we expose the myelum and create mild SCI model with 20gr and severe SCI with 35gr aneurysm clips. ACTH4-10Pro8-Gly9-Pro10 was administered intranasally to the treatment group and 0,9% NaCl to the control group (placebo). Both group was remain alive and terminated at 3 and 6 hour. The preparations tissue sample were fixed in formalin and examined for immunohistochemistry. Quantitative measurement of anti-inflammatory cytokine (IL-4, IL-10, IL-13) was done in posterior horn with associated anti-monoclonal antibodies.

 

Result: Rats with mild SCI that were given ACTH4-10Pro8-Gly9-Pro10 shown greater expression of IL-4, IL-10 and IL-13 at three hour post compression but only IL-10 and IL-13 elevated significantly at six hour. Rats with severe compression in ACTH4-10Pro8-Gly9-Pro10 group shown greater expression of IL-10, IL-13 at three hour and IL-4, IL-10 at six hour compared with the placebo group.

 

Conclusion: Administration of ACTH4-10Pro8-Gly9-Pro10 intranasal can increase anti inflammatory cytokine expression at Sprague Dawley rat model with mild and severe SCI. Expression of anti inflammatory cytokine was greater in mild compression and early hour (3 hour). Further research needs to be done to determine optimal dose and the actual clinical outcome in vivo.