All‐trans‐retinoic acid attenuates cell swelling and mitochondrial dysfunction following oxygen‐glucose deprivation in glial cells

Astrocyte swelling is an integral component of cytotoxic brain edema in ischemic injury. While mechanisms underlying astrocyte swelling are multifactorial, oxidative stress and mitochondrial dysfunction are contributing factors. All‐trans‐retinoic acid (ATRA) is a vitamin A derivative that is important in neuronal patterning, survival, and neurite outgrowth. Neuroprotective effects of ATRA in ischemic injury have also been demonstrated but its effects on glial swelling are not known. We investigated the protective effects of ATRA on cell swelling and depolarization of the inner mitochondrial membrane potential (Δ Îm) in ischemic injury. C6 glial cells were subjected to oxygen‐glucose deprivation (OGD) and cell volume was determined 90 min after the end of OGD. OGD increased cell volume by 27% but this increase was significantly attenuated by ATRA. Mitochondrial dysfunction, a key component of ischemic injury, contributes to cell swelling. OGD induced a 36% decline in mitochondrial Δ Îm but this decline was attenuated by ATRA. Our results indicated an acute effect of ATRA on cell swelling and the decline in Δ Îm and some of its protective effects may be through reducing mitochondrial injury. Considering the paucity of agents in attenuating brain edema in ischemia, ATRA has the potential to reduce brain edema and associated neural damage in ischemic injury. Supported by ARS/USDA.