Neuroprotection by chitosan nanoparticles in oxidative stress-mediated injury

Oxidative stress is a critical component of nervous system secondary injury. Oxidative stress produces toxic chemical byproducts including reactive aldehydes that traverse intact membranes and attack neighboring healthy cells. This secondary damage often leads to further patho-biochemical cascades that exacerbate the original insult. In this work, we investigate the therapeutic effects of chitosan nanoparticles on cell cultures exposed to oxidative stress.

We found chitosan nanoparticles can rescue BV-2 glial cells from death, but only for cells undergoing necrosis. Necrosis occurred when cultures were challenged with high concentrations of H₂O₂ (> 110 μM) whereas a slow and progressive loss of cultures was observed in more dilute (50-100 μM) peroxide applications. In the latter case, the primary mode of cell death was apoptosis. These studies revealed that while rescue of H₂O₂ challenged cultures was achieved for necrotic cell death, no such sparing was observed in apoptotic cells. Based on the current and cumulative data regarding the membrane fusogenic properties of chitosan, we conclude that chitosan neuroprotection arises from its membrane sealing effects. Consistent with this hypothesis is the observation that apoptotic cells did not exhibit early stage membrane damage. These in vitro results elucidate mechanisms by which membrane fusogens may provide therapeutic benefit.