Cellular mechanisms of neurodegeneration and neuroprotection in the mammalian cortex

Neurodegeneration, a leading cause of morbidity and mortality, results from progressive CNS dysfunction and cell death. This dissertation investigates neuroprotective and neurodegenerative mechanisms using two approaches. First, studies in sex-segregated neurons and astrocytes examined isoflurane preconditioning and 17β-estradiol effects on survival following oxygen-glucose deprivation, revealing sex-independent protection by isoflurane and estradiol-mediated modulation in female neurons. Second, experiments assessed cyclophilin D’s role in cell death, showing its involvement in oxidant-induced injury but not excitotoxic or energetic stress. Findings highlight sex-specific neuroprotective responses and identify cyclophilin D as a mediator of oxidative damage, informing strategies to mitigate neurodegeneration.