Cynomolgus Monkey Brain (NHP-TI126)

This paper yields comprehensive research regarding the neurotoxic effects of dexmedetomidine compared to ketamine in the brains of fetal Cynomolgus monkeys. The study highlights the apprehension of anesthetics as a neurodegenerative effect on the developing brains, with special reference to the prospective neuroprotective properties of dexmedetomidine vs. anesthesia-induced neuronal injury. The histopathological examinations and NHP pharmacokinetic analysis, therefore, assessed neurotoxic effects and showed that, in a well-designed experimental setting, high doses of dexmedetomidine did not produce significant neuroapoptosis or neurodegeneration in the frontal cortex of the developing brain. This is an important finding that illustrates, in sharp contrast, the safety profile of dexmedetomidine versus the marked neurotoxicity seen with ketamine administration in the context of pediatric anesthesia. This study has the in-depth importance of guiding anesthetic practices in the safer development of neonatal and pediatric care. Therefore, it further illuminates the need for more research on anesthetic developmental neurotoxicity.

¹Fig. 1. Activated caspase 3 (AC3) immunostained photomicrographs of the frontal cortex of fetal monkey brains of untreated control (A) and monkevs treated with ketamine (B). low-dose dexmedetomidine (C). and high-dose dexmedetomidine (D). Arrows in Fig.2B indicate AC3-positive cells.10X magnification.

¹Fig. 2. Activated caspase 3 (AC3) immunostained photomicrographs of the frontal cortex of fetal monkey brains of untreated control(A) and monkeys treated with ketamine (B), low-dose dexmedetomidine (C), and high-dose dexmedetomidine. The AC3-positive cells shown in Fig. 2B can be clearly seen in Fig. 3B. 20X magnification.

¹Fig. 3. Immunohistochemical TUNEL-label photomicrograhs of the frontal cortex of fetal monkey brains of untreated control(A and monkeys treated with ketamine (B), low-dose dexmedetomidine (C), and high-dose dexmedetomidine (D). TUNEL. labeled cells as a result of ketamine treatment are clearly seen as brown cells in Fig. 4B. 20X magnification.

¹Fig. 4. Immunohistochemical TUNEL-label photomicrograhs of the frontal cortex of fetal monkey brains of untreated control(A and monkeys treated with ketamine (B), low-dose dexmedetomidine (C), and high-dose dexmedetomidine (D). TUNEL. labeled cells as a result of ketamine treatment are clearly seen as brown cells in Fig. 4B. 20X magnification.

Reference

1. Edward Koo., et al. " Neurotoxic effects of dexmedetomidine in fetal cynomolgus monkey brains." The Journal of Toxicological Sciences. 2014, 39: 251–262