Astrocytic nutritional dysfunction associated with hypoxia-induced neuronal vulnerability in stroke-prone spontaneously hypertensive rats

Stroke-prone spontaneously hypertensive rats (SHRSP) is a valuable animal model to investigate human strokes. SHRSP Izumo strain (Izm) neurons are highly sensitive to blood supply changes. Furthermore, SHRSP/Izm astrocytes show various abnormalities upon hypoxic stimulation compared to control Wistar Kyoto (WKY/Izm) rats. This study aimed to describe stroke-related characteristics of SHRSP/Izm-derived neurons and astrocytes. In addition, we discuss the role of astrocytes in the development of stroke in SHRSP/Izm model. In SHRSP/Izm, neuronal death is induced upon reoxygenation after hypoxia. Furthermore, it was shown that SHRSP/Izm astrocytes show significantly reduced lactate production and supply ability to nerve cells when subjected to hypoxic stimulation. In particular, decreased lactate production and monocarboxylic acid transporter (MCT) expression in SHRSP/Izm astrocytes are factors that induce neuronal cell death. Remarkable differences in glial cell line-derived neurotrophic factor (GDNF) expression and L-serine production were also observed in SHRSP/Izm-derived astrocytes compared to WKY/Izm. Reduced production of both GDNF and L-serine contributes to diminished neuronal survival. The differences between SHRSP/Izm and WKY/Izm astrocyte cellular properties may contribute to compromised neuronal nutrition and induction of neuronal death. These properties are likely to be the factors that enhance stroke in SHRSP/Izm.

Keywords: Astrocytes; Glial cell line-derived neurotrophic factor; L-serine; Lactate; Stroke-prone spontaneously hypertensive rats.