The work by Planel et al. shows that a treatment with anesthetic chloral hydrate, pentobarbital sodium, or isoflurane can induce tau hyperphosphorylation via inhibition of phosphatase activity by hypothermia in mice. The anesthesia was induced by intraperitoneal injections of chloral hydrate (500 mg/kg), pentobarbital sodium (100 mg/kg) or by exposure to inhaled isoflurane. The results suggest that the changes in tau phosphorylation were not a result of anesthesia per se, but rather a consequence of anesthesia-induced hypothermia. Since hypothermia can happen in the operation room, these studies indicate that it is important to maintain normal temperature for patients under surgery.

Chloral hydrate and pentobarbital sodium are not clinical anesthetics; therefore, the clinical relevance of the present results is unclear. Moreover, mice may develop hypotension, hypoxia, and hypercapnia [Editor’s note: i.e., blood carbon dioxide overload] following the anesthesia, which could affect Alzheimer disease neuropathogenesis, as well. Data of blood pressure and blood gas after...  Read more

The work by Planel et al. shows that a treatment with anesthetic chloral hydrate, pentobarbital sodium, or isoflurane can induce tau hyperphosphorylation via inhibition of phosphatase activity by hypothermia in mice. The anesthesia was induced by intraperitoneal injections of chloral hydrate (500 mg/kg), pentobarbital sodium (100 mg/kg) or by exposure to inhaled isoflurane. The results suggest that the changes in tau phosphorylation were not a result of anesthesia per se, but rather a consequence of anesthesia-induced hypothermia. Since hypothermia can happen in the operation room, these studies indicate that it is important to maintain normal temperature for patients under surgery.

Chloral hydrate and pentobarbital sodium are not clinical anesthetics; therefore, the clinical relevance of the present results is unclear. Moreover, mice may develop hypotension, hypoxia, and hypercapnia [Editor’s note: i.e., blood carbon dioxide overload] following the anesthesia, which could affect Alzheimer disease neuropathogenesis, as well. Data of blood pressure and blood gas after anesthesia would be useful to assess these potential effects.

Isoflurane is in clinical use. Recent studies (Eckenhoff et al., 2004; Xie et al., 2006; Xie et al., 2007) showed that a treatment with 1.2 to 2.5 percent isoflurane for 6 hours can enhance Aβ oligomerization, affect APP processing, and increase Aβ generation in cultured cells. In Fig. 2 of the present study, the authors show that anesthesia under the conditions used affected neither APP processing nor Aβ levels in mouse brain. However, the concentration of isoflurane and duration of exposure to isoflurane have not been provided in the studies. For this reason, it is difficult to determine the effects of isoflurane on APP processing and Aβ generation based solely on these experiments. It is conceivable that a treatment with different concentrations of isoflurane and different exposure times may affect APP processing and Aβ levels.

More in vivo studies systematically assessing the effects of clinically relevant anesthetics (e.g., isoflurane, sevoflurane, desflurane, propofol, morphine, fentanyl) on APP processing, Aβ generation, and tau protein metabolism are warranted before we can conclude whether anesthesia itself versus anesthesia-induced hypothermia can affect Alzheimer disease neuropathogenesis.

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