Neuroprotective effects of ACTH4-10PRO8-GLY9-PRO10 on the ketamine-induced neurotoxicity in neonatal rats: increased BDNF expression and BDNF serum concentrations

Abstract

Background: ACTH4-10Pro8-Gly9-Pro10, a synthetic adrenocorticotropic hormone analogue lacking hormonal
effects, was investigated for its neuroprotective effects against ketamine-induced neurotoxicity in neonatal rats.
Methodology: This experimental study employed a post-test-only control group design with simple randomization and double blinding. Forty-two male Sprague-Dawley rats (7 days old, 15–20 g) were divided into three groups (n=14): control, ketamine (40 mg/kg BW subcutaneously), and ACTH4-10Pro8-Gly9-Pro10 (50 mcg/kg BW intranasally) + ketamine. BDNF expression in the cortex and hippocampus tissues and serum BDNF levels were analyzed.
Results: ACTH4-10Pro8-Gly9-Pro10 pretreatment significantly increased the percentage of BDNF-expressing cells compared to the ketamine group (31.0±7.9%, P = 0.001). Serum BDNF levels were higher in the treatment group, but the difference was not statistically significant (P = 0.723).
Conclusion: ACTH4-10Pro8-Gly9-Pro10 demonstrates neuroprotective potential against ketamine-induced
neurotoxicity in neonatal rats by increasing BDNF expression, although not serum levels.
Keywords: ACTH4-10Pro8-Gly9-Pro10; BDNF; Ketamine-induced neurotoxicity; Apoptosis
Citation: Natapraja TK, Prasetya RJ. Neuroprotective effects of ACTH4-10PRO8-GLY9-PRO10 on the ketamineinduced neurotoxicity in neonatal rats: increased BDNF expression and BDNF serum concentrations. Anaesth. pain intensive care 2026;30(1):75-80 DOI: 10.35975/apic.v30i1.3105
Received: July 21, 2025; Revised: September 01, 2024; Accepted: September 05, 2025