Mechanism of Acute Ischemic Injury of Oligodendroglia in Early Myelinating White Matter: The Importance of Astrocyte Injury and Glutamate Release

This is the authors' abstract. We don't add key points for this paper.

In developing CNS white matter (WM), the period of early myelination is characterized by a heightened sensitivity to ischemic injury. Using an in situ (isolated) preparation, we show that the mechanism of acute ischemic injury of immature WM oligodendroglial involves Ca2+ influx though non-NMDA type glutamate receptors (GluRs). The Ca2+-influx and acute cell death that was evoked by ischemic conditions (oxygen and glucose withdrawal) in identified P10 rat optic nerve oligodendroglia were blocked by removing extracellular Ca2+ or by CNQX, a selective non-NMDA GluR antagonist. The selective Na-K-Cl cotransport (NKCC) inhibitor bumetanide was also highly protective, even though NKCC expression is restricted to astrocytes in this tissue. Bumetanide largely prevented the non-NMDA GluR-mediated [Ca2+]i rise evoked by ischemia in oligodendroglia, suggesting that it interfered with ischemic glutamate release. In control WM, glutamate-like reactivity was located mainly in astrocytes and oligodendroglia identified using ultrastructural criteria. In ischemic WM, astrocyte glutamate-like reactivity was reduced, an effect countered by bumetanide. We suggest a model in which NKCC-dependent injury and release of glutamate from astrocytes activates glutamate receptors on oligodendroglia, resulting in Ca2+-influx and acute cell death.