Date of Completion

Spring 5-1-2022

Thesis Advisor(s)

Roslyn Holly Fitch, Joseph LoTurco

Honors Major

Biological Sciences

Abstract

This study investigated the neuroprotective effects of caffeine, a common treatment for infant respiratory distress. Caffeine is often given to preterm infants to enhance respiratory drive. Many of these same infants are at risk for hypoxia-ischemia (HI) -- a brain injury that occurs due to a lack of blood and oxygen supply to the brain and involves tissue loss. This injury can lead to major consequences such as learning and motor disorders such as cerebral palsy. Although caffeine has been widely used to increase respiratory drive in preterm infants, some emergent research suggests it may have secondary benefits in protecting against brain damage. However, the mechanism for how caffeine acts on the brain as a neuroprotectant is not well understood. The current research addresses this gap by investigating the protective mechanism of caffeine on microglia activation. Infant rats were separated into four conditions that included an injury simulating HI or a sham injury, and treatment with saline or caffeine solution. Groups thus included: Sham saline, Sham caffeine, HI saline, and HI caffeine. Subjects were sacrificed 48 hours after birth and measured for chromatin condensation (using a DAPI stain) and microglial soma area (using an IBA stain). Given putative beneficial effects of caffeine on HI, we posited that caffeine may act by reducing microglial over activation. If true, the HI saline groups should have the largest microglial soma area and smallest DAPI density (indicating chromatin condensation), while HI caffeine subjects should look more like shams. Preliminary research supports this hypothesis in males only, but not females -- even though protective effects of caffeine were observed in both sexes. Applications of the current data will provide valuable insights in modifying the caffeine HI therapy technique that can be used to prevent neural tissue loss and poor outcomes in preterms.

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