• Jun Zhang, Yuanlin Dong, Zhipeng Xu, Yiying Zhang, Chuxiong Pan, Sayre McAuliffe, Fumito Ichinose, Yun Yue, Weimin Liang, and Zhongcong Xie.
• Geriatric Anesthesia Research Unit, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Room 4310, Charlestown, MA 02129-2060, USA.
• Anesth. Analg.. 2011 Dec 1;113(6):1468-75.

Backgroundβ-Amyloid protein (Aβ) accumulation and caspase activation have been shown to contribute to Alzheimer disease neuropathogenesis. Aβ is produced from amyloid precursor protein through proteolytic processing by aspartyl protease β-site amyloid precursor protein-cleaving enzyme (BACE). The inhaled anesthetic isoflurane has been shown to induce caspase activation and increase levels of BACE and Aβ. However, the underlying mechanisms and interventions of the isoflurane-induced neurotoxicity remain largely to be determined. The glucose analog 2-deoxy-d-glucose (2-DG) has neuroprotective effects. Therefore, we sought to determine whether 2-DG can reduce caspase-3 activation and the increase in the levels of BACE and reactive oxygen species (ROS) induced by isoflurane.MethodsH4 human neuroglioma cells were treated with saline or 2-DG (5 mM) for 1 hour followed by a control condition or 2% isoflurane for 6 hours. The levels of caspase-3 cleavage (activation), BACE, cytosolic calcium, and ROS were determined. Two-way analysis of variance was used to assess the interactions of 2-DG and isoflurane on caspase-3 activation, and levels of BACE and ROS.ResultsIn H4 human neuroglioma cells, 2-DG reduced the caspase-3 activation (477% vs 186%, F = 8.68; P = 0.019) and the increase in BACE levels (345% vs 123%, F = 42.24; P = 0.0002) induced by isoflurane. 2-DG decreased the levels of cytosolic calcium and ROS (100% vs 66%, F = 1.94; P = 0.014).ConclusionsThese results suggest that 2-DG may decrease oxidative stress and increase cytosolic calcium levels, thus attenuating isoflurane-induced neurotoxicity.

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