The detrimental role of glial acidification during ischemia

Abstract

In this issue of Neuron, Beppu et al. (2014) demonstrate that glial acidification during ischemia contributes to neurotoxicity. Using a suite of in vivo optogenetic tools, the authors are able to exacerbate or attenuate neuronal damage during ischemia with glial acidification or alkalization, respectively.

Figure 1. A Model for Ischemia-Induced Excitotoxicity

Without a steady blood supply, oxygen, glucose, and ATP levels decline quickly in the ischemic region. As a result, lactate begins to accumulate in astrocytes, acidifying the intracellular space. Glial acidification is correlated with neuronal cell death, and alkalization is capable of attenuating the full neurotoxic effects. Whether a mechanism for glial glutamate release exists in response to declining cytoplasmic pH remains to be elucidated. The absence of ATP prevents the energy-dependent maintenance of normal ionic gradients. Consequently, glutamate transporters that are typically responsible for clearing extracellular glutamate begin to run in reverse and expel glutamate from astrocytes and neurons. Increased extracellular glutamate levels activate glutamate receptors on neurons, which then leads to the toxic influx of calcium.