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Neuropharmacology. 2020 Feb;163:107853. doi: 10.1016/j.neuropharm.2019.107853. Epub 2019 Nov 14.

Mild hypothermia protects synaptic transmission from experimental ischemia through reduction in the function of nucleoside transporters in the mouse hippocampus.

Author information

1
Department of Pharmacology, Jikei University School of Medicine, Minato-ku, Tokyo, 105-8461, Japan.
2
Department of Pharmacology, Jikei University School of Medicine, Minato-ku, Tokyo, 105-8461, Japan. Electronic address: m.kawamura@jikei.ac.jp.

Abstract

Ischemia, a severe metabolic stress, increases adenosine levels and causes the suppression of synaptic transmission through adenosine A1 receptors. Although temperature also regulates extracellular adenosine levels, the effect of temperature on ischemia-induced activation of adenosine receptors is not yet fully understood. Here we examined the role of adenosine A1 receptors in mild hypothermia-mediated neuroprotection during the acute phase of ischemia. Severe ischemia-induced neurosynaptic impairment was reproduced by oxygen-glucose deprivation at normothermia (36 °C) and assessed with extracellular recordings or whole-cell patch clamp recordings in acute hippocampal slices in mice. Mild hypothermia (32 °C) induced the protection of synaptic transmission by activating adenosine A1 receptors. Stricter hypothermia (28 °C) caused additional neuroprotective effects by extending the onset time to anoxic depolarization; however, this effect was not associated with adenosine A1 receptors. The response of exogenous adenosine-induced inhibition of hippocampal synaptic transmission was increased by lowering the temperature to 32 °C or 28 °C. Hypothermia also reduced the function of dipryidamole-sensitive nucleoside transporters. These findings suggest that an increased response of adenosine A1 receptors, caused by a reduction in the function of nucleoside transporters, is one mechanism by which therapeutic hypothermia (usually used within the mild range) mediates neurosynaptic protection in the acute phase of stroke.

KEYWORDS:

Acute hippocampal slices; Adenosine A(1) receptors; Field recordings; Patch clamp; Therapeutic hypothermia

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