MilliporeSigma
  • Home
  • Search Results
  • Sevoflurane preconditioning-induced neuroprotection is associated with Akt activation via carboxy-terminal modulator protein inhibition.

Sevoflurane preconditioning-induced neuroprotection is associated with Akt activation via carboxy-terminal modulator protein inhibition.

British journal of anaesthesia (2014-09-04)
Y Chen, H Nie, L Tian, L Tong, J Deng, Y Zhang, H Dong, L Xiong
ABSTRACT

Sevoflurane preconditioning has a neuroprotective effect, but the underlying mechanism is not fully understood. The aim of the present investigation was to evaluate whether sevoflurane-induced cerebral preconditioning involves inhibition of carboxy-terminal modulator protein (CTMP), an endogenous inhibitor of Akt, in a rat model of focal cerebral ischaemia. Male Sprague-Dawley rats were exposed to 2.7% sevoflurane for 45 min. One hour later, rats were subjected to 60 min of focal cerebral ischaemia. The phosphoinositide 3-kinase inhibitors wortmannin and LY294002 were administered 10 min before preconditioning. Rats in the lentiviral transduction group received an intracerebroventricular injection of lentiviral vector Ubi-MCS-CTMP 3 days before ischaemia. Neurological deficits and infarct volumes were evaluated 24 h and 7 days after reperfusion. Phosphorylation of Akt, glycogen synthase kinase-3β (GSK3β), and expression of CTMP were determined at 1, 3, 12, and 24 h after reperfusion. Akt activity was measured at 3 h after reperfusion. Sevoflurane preconditioning improved neurological score and reduced infarct size at 24 h of reperfusion. Pretreatment with wortmannin or LY294002 attenuated these neuroprotective effects. Expression of CTMP correlated with reduced Akt activity after ischaemia, while sevoflurane preconditioning preserved Akt activity and increased phosphorylation of GSK3β. CTMP over-expression diminished the beneficial effects of sevoflurane preconditioning. Activation of Akt signalling via inhibition of CTMP is involved in the mechanism of neuroprotection provided by sevoflurane preconditioning.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Titanium tetrachloride, packaged for use in deposition systems
Supelco
Carbon dioxide (99.8%), cylinder of 14 L, analytical standard
Supelco
Carbon dioxide (99.8%), cylinder of 48 L, analytical standard
Sigma-Aldrich
Carbon dioxide, ≥99.8%
Sigma-Aldrich
Titanium(IV) chloride solution, 1.0 M in toluene
Sigma-Aldrich
Titanium(IV) chloride solution, 0.09 M in 20% HCl
Sigma-Aldrich
Titanium(IV) chloride solution, 1.0 M in methylene chloride
Sigma-Aldrich
Carbon-12C dioxide, 99.9 atom % 12C
Sigma-Aldrich
Carbon-12C dioxide, 99.99 atom % 12C
Sevoflurane, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Titanium(IV) chloride, ≥99.995% trace metals basis
Sigma-Aldrich
Titanium(IV) chloride, ReagentPlus®, 99.9% trace metals basis