Vitamin E Decreases Cytotoxicity and Mitigates Inflammatory and Oxidative Stress Responses in a Ferret Organotypic Brain Slice Model of Neonatal Hypoxia-Ischemia

The gyrencephalic ferret brain is an excellent model in which to study hypoxia-ischemia (HI), a significant contributor to neurological injury in neonates. Vitamin E, an essential fat-soluble antioxidant, reduces oxidative stress and inflammation in both animal models and neonates. The aim of this study was to assess the effects of Vitamin E after oxygen glucose deprivation (OGD) in an organotypic ferret brain slice model of neonatal HI. We hypothesized that Vitamin E would decrease cytotoxicity, inflammation, and oxidative stress in OGD-exposed brain slices. Term-equivalent ferrets were sacrificed at postnatal (P) day 21-23 and 300 µM whole hemisphere brain slices were obtained. During a 24h rest period, slices were cultured in either non-treated control conditions or with Erastin, a promotor of oxidative stress. Slices were then exposed to 2h of OGD followed by Vitamin E (25-100 IU/kg), Erastin (10µM) or Ferrostatin (1µM ), an inhibitor of ferroptosis. Relative cytotoxicity was determined using an LDH assay, cell death was quantified via nuclear propidium iodide (PI) staining, oxidative stress was quantified via cellular GSH (glutathione) levels and target genes responsive to oxidative stress and inflammation were e valuated by qRT-PCR. OGD increased cytotoxicity, which was significantly reduced by treatment with Vitamin E. Vitamin E also preserved GSH after OGD and decreased amplification of certain markers of oxidative stress (CHAC1, SLC7A11) and inflammation (TNF-alph...
Source: Developmental Neuroscience - Category: Neuroscience Source Type: research