Acth4-10pro8-Gly9-Pro10 Administration Attenuate Ketamine-Induced Neurotoxicity in Post Natal Day-7 (Pnd-7) Rats: Effect on Caspase-3, Bcl-2, and BDNF Activity

Author(s): Raka Jati Prasetya*, Gontar A. Siregar, Nazaruddin Umar, Yetty Machrina, Sri Raharjo, Delfitri Munir, Dadik Wahyu Wijaya and Juliandi Harahap


Introduction: Ketamine is widely used as an anesthetic agent for children because of its safety and high efficacy in maintaining analgesia, spontaneous breathing, and hemodynamic stability. Nevertheless, recent studies showed ketamine exposure might compromise brain synaptogenesis, particularly in the growth spurt period of young animals. Here we investigate the neuroprotective effects of administration of ACTH4-10Pro8-Gly9-Pro10 can decrease neurotoxicity againts ketamine in PND-7 Sprague Dawley rats by investigating caspase-3, Bcl-2, and BDNF expression in the cortex and hipocampal tissue

Methods: Subjects were PND-7 Sprague Dawley rats (n=33) and separated into three groups: K1–intranasal placebo and subcutaneous placebo treatment, K2–intranasal placebo and subcutaneous ketamine treatment, and K3–intranasal ACTH4-10Pro8-Gly9-Pro10 one hour before subcutaneous ketamine treatment. All rats were decapitated 6 hours after treatment, then the expression of caspase-3, Bcl-2, and BDNF in cortex and hipocampal tissue was interpreted by immunohistochemistry methods and ImageJ software.

Results: Thirty-three subjects were involved; two rats in K1 and one in K3 died. The mean expressions in K2 and K3 of caspase-3 were 34.1 ± 4.8 and 30.3 ± 7.3 (p=0.178), Bcl-2 were 23.0 ± 13.3 and 23.0 ± 18.3 (p=0.99), and BDNF were 19.9 ± 4.9 and 31.0 ± 7.9 (p=0.001), respectively

Conclusion: In conclusion, ACTH4-10Pro8-Gly9-Pro10 administration can attenuate ketamine-induced neurotoxicity in post natal day-7 rats and reduce distribution of the percentage of cells expressing BDNF significantly, but there was no significant difference in the distribution of the percentage of cells expressing caspase-3 and Bcl-2

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