Doctor of Philosophy
Date of Defense
George T. Taylor
Michael Griffin, Ph.D.
Each year, millions of premature babies are exposed to sedative/anesthetic drugs (SADs) in the neonatal intensive care unit (NICU). Acute exposure to SADs triggers widespread apoptosis in the developing brain of rodents and non-human primates. Furthermore, premature infants are administered caffeine (CAF) to treat respiratory dysfunction. Mounting evidence suggests that CAF may be neurotoxic and, when given in combination with SADs, potentiates SAD-induced cell death. However, the apoptotic interaction of CAF and SAD co-exposure is poorly understood. In a series of studies, I report that CAF combined with the NICU SADs midazolam, ketamine, or fentanyl is more neurotoxic to the postnatal day 3 (PND3) mouse brain than either CAF or SAD alone. Since many premature infants are given CAF + SADs chronically, I tested whether multiple exposures of CAF + SAD at PND3 + PND6 is more detrimental to the developing brain than a single exposure at PND6. My results indicate that the PND6 mouse brain is as vulnerable to multiple exposures of CAF + SAD on PND3 and PND6 as it is to a single exposure on PND6. Based on these results, neonatologists should exercise caution by limiting CAF + SADs co-exposure to durations necessary to ensure the survival of babies born prematurely.
Cabrera, Omar Hosea, "Caffeine Combined with Sedative/Anesthetic Drugs Used in Neonatal Medicine and Apoptotic Neurotoxicity in Developing Mouse Brain" (2016). Dissertations. 107.