title: Isoflurane preconditioning improves short-term and long-term neurological outcome after focal brain ischemia in adult rats.
abstract: Isoflurane preconditioning improved short-term neurological outcome after focal brain ischemia in adult rats. It is not known whether desflurane induces a delayed phase of preconditioning in the brain and whether isoflurane preconditioning-induced neuroprotection is long-lasting. Two months-old Sprague-Dawley male rats were exposed to or were not exposed to isoflurane or desflurane for 30 min and then subjected to a 90 min middle cerebral arterial occlusion (MCAO) at 24 h after the anesthetic exposure. Neurological outcome was evaluated at 24 h or 4 weeks after the MCAO. The density of the terminal deoxynucleotidyl transferase biotinylated UTP nick end labeling (TUNEL) positive cells in the penumbral cerebral cortex were assessed 4 weeks after the MCAO. Also, rats were pretreated with isoflurane or desflurane for 30 min. Their cerebral cortices were harvested for quantifying B-cell lymphoma-2 (Bcl-2) expression 24 h later. Here, we showed that pretreatment with 1.1% or 2.2% isoflurane, but not with 6% or 12% desflurane, increased Bcl-2 expression in the cerebral cortex, improved neurological functions and reduced infarct volumes evaluated at 24 h after the MCAO. Isoflurane preconditioning also improved neurological functions and reduced brain infarct volumes in rats evaluated 4 weeks after the MCAO. Isoflurane preconditioning also decreased the density of TUNEL-positive cells in the penumbral cerebral cortex. We conclude that isoflurane preconditioning improves short-term and long-term neurological outcome and reduces delayed cell death after transient focal brain ischemia in adult rats. Bcl-2 may be involved in the isoflurane preconditioning effect. Desflurane pretreatment did not induce a delayed phase of neuroprotection.
authors.affiliation: Department of Anesthesiology, University of Virginia, 1 Hospital Drive, Charlottesville, VA 22908, USA.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: Z
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000077335:Desflurane; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007530:Isoflurane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D000077335:Desflurane; D007530:Isoflurane
references.citation: Circulation. 1986 Nov;74(5):1124-36
references.pmid: 3769170
references.citation: Brain Res. 2004 Sep 17;1021(1):76-81
references.pmid: 15328034
references.citation: J Cereb Blood Flow Metab. 2007 Jun;27(6):1108-28
references.pmid: 17047683
references.citation: J Cereb Blood Flow Metab. 1990 Mar;10(2):290-3
references.pmid: 1689322
references.citation: Early Hum Dev. 1979 Mar;3(1):79-83
references.pmid: 118862
references.citation: Anesthesiology. 2007 Jan;106(1):92-9; discussion 8-10
references.pmid: 17197850
references.citation: Stroke. 1999 Dec;30(12):2752-8
references.pmid: 10583007
references.citation: Brain Res Brain Res Rev. 1990 Jan-Apr;15(1):41-70
references.pmid: 2163714
references.citation: Anesthesiology. 2004 Dec;101(6):1313-24
references.pmid: 15564938
references.citation: Brain Res. 2007 Jun 4;1152:201-8
references.pmid: 17434151
references.citation: J Neurol Sci. 1994 Aug;125(1):3-10
references.pmid: 7964886
references.citation: Neuroscience. 2008 Jun 26;154(3):1002-8
references.pmid: 18495358
references.citation: J Cereb Blood Flow Metab. 1995 May;15(3):389-97
references.pmid: 7713996
references.citation: Stroke. 1997 Oct;28(10):2060-5; discussion 2066
references.pmid: 9341719
references.citation: Brain Res Bull. 1993;31(5):565-72
references.pmid: 8495380
references.citation: Brain Res. 1986 May 28;374(2):244-8
references.pmid: 3719335
references.citation: Anesthesiology. 2007 Dec;107(6):963-70
references.pmid: 18043065
references.citation: Anesth Analg. 2003 Jan;96(1):233-7, table of contents
references.pmid: 12505958
references.citation: Stroke. 1993 Jan;24(1):117-21
references.pmid: 8418534
references.citation: J Cereb Blood Flow Metab. 1993 Jul;13(4):541-9
references.pmid: 8314910
references.citation: Eur J Pharmacol. 2008 May 31;586(1-3):106-13
references.pmid: 18355806
references.citation: J Neuropathol Exp Neurol. 2006 Oct;65(10):945-52
references.pmid: 17021399
references.citation: Ann Thorac Surg. 2005 Feb;79(2):532-6; discussion 537
references.pmid: 15680829
references.citation: Anesthesiology. 2008 Apr;108(4):643-50
references.pmid: 18362596
references.citation: Anesth Analg. 2007 May;104(5):1066-77, tables of contents
references.pmid: 17456654
references.citation: Anesthesiology. 2000 May;92(5):1335-42
references.pmid: 10781279
references.citation: Am J Pathol. 1993 Feb;142(2):623-35
references.pmid: 8434652
references.citation: Anesthesiology. 2009 Feb;110(2):231-8
references.pmid: 19194149
references.citation: Science. 1997 Feb 21;275(5303):1129-32
references.pmid: 9027314
references.citation: Mol Pharmacol. 2004 May;65(5):1172-80
references.pmid: 15102945
references.citation: Anesthesiology. 2001 Sep;95(3):734-9
references.pmid: 11575548
references.citation: Ann Vasc Surg. 2005 Jan;19(1):1-4
references.pmid: 15714359
references.citation: J Pharmacol Exp Ther. 2001 May;297(2):474-8
references.pmid: 11303032
references.citation: Neuroscience. 2003;118(1):99-106
references.pmid: 12676141
references.citation: Stroke. 2002 Jul;33(7):1889-98
references.pmid: 12105371
references.citation: Brain Dev. 1997 Jul;19(5):326-38
references.pmid: 9253485
references.citation: Trends Neurosci. 2003 May;26(5):248-54
references.pmid: 12744841