USING ANTIOXIDANT COMPOUNDS TO REVERSE HIPPOCAMPAL CELLULAR AND PHYSIOLOGICAL DEFICITS CAUSED BY OXYGEN GLUCOSE DEPRIVATION

Ischemic stroke is a global leading cause of death and disability. The sudden cessation of blood flow results in low oxygen and nutrient delivery, substantially altering cellular function. The hippocampus, a brain region crucial for learning and memory, is especially vulnerable to stroke, resulting in neuronal cell death and changes in synaptic transmission and plasticity. Classically, stroke can be modelled in vitro using oxygen glucose deprivation (OGD). Using in vitro models, we explored the effects of OGD on synaptic transmission in the CA1 region of the hippocampus and on cell viability and cytotoxicity in hippocampal HT22 cells. Measuring excitatory post synaptic potentials (EPSP) we show that 20-min of OGD exposure resulted in an irreversible impairment of EPSP (65.1±12.3% of baseline, n=12). In HT22 cells 4h of OGD exposure resulted in decreased cell viability (70.5±9.3% of control, n=5) and increased cytotoxicity (1.2±0.07, n=3). These deficits in synaptic transmission were reversed using the antioxidants, N-acetyl-cysteine (NAC) (107.6±5.9%, n=6) and Coenzyme Q10 (CoQ10) (101.2±8.6%, n=5). Preliminary data using NAC also demonstrated improved cell viability (107.2%, n=2). However, treatment with antioxidants failed to restore long term potentiation (LTP) in hippocampal slices. LTP following treatment with NAC (114.2±5.6%, n=5) and CoQ10 (100.5±3.9%, n=5) was markedly lower than control LTP (133.4±5.0%, n=13). Ultimately these results suggest that antioxidants can improve synaptic transmission and cell viability but fail to improve synaptic plasticity following OGD and future investigations will explore the underlying proteomic and molecular changes causing these results.