Considerations for the use of anesthetics in neurotoxicity studies.
Anesthetics are widely used in experiments investigating neurotoxicity and neuroprotection; however, these agents are known to interfere with the outcome of these experiments. The purpose of this overview is to review these effects and suggest methods for minimizing unintended consequences on experimental outcomes. Information on the neuroprotective and neurotoxic effects of isoflurane, dexmedetomidine, propofol, ketamine, barbiturates, halothane, xenon, carbon dioxide, and nitrous oxide is summarized. The pertinent cell signaling pathways of these agents are discussed. Methods of humane animal euthanasia without anesthetics are considered. Most anesthetics alter the processes of neuronal survival and death. When designing survival surgeries, sham controls subjected to anesthesia but not the surgical intervention should be compared with controls subjected to neither anesthesia nor surgery. Additional controls could include using an anesthetic with a different mechanism of action from the primary anesthetic used. Because the effects of anesthetics lessen with time after surgery, survival surgeries should include later time points until at least 7 d after the procedure. Humane methods of animal euthanasia that do not require anesthetics exist and should be used whenever appropriate.
Karmarkar
Sumedha W
SW
Department of Pharmacology, School of Medicine, Southern Illinois University, Springfield, IL, USA.
Bottum
Kathleen M
KM
Tischkau
Shelley A
SA
D000777:Anesthetics / Q000494:pharmacology*; D001463:Barbiturates; D002245:Carbon Dioxide; D020927:Dexmedetomidine; D037901:Euthanasia, Animal / Q000379:methods*; D006221:Halothane; D007530:Isoflurane; D007649:Ketamine; D009420:Nervous System / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009609:Nitrous Oxide; D015742:Propofol; D012106:Research; D015398:Signal Transduction / Q000187:drug effects*; D014116:Toxicology / Q000379:methods*; D014978:Xenon
D000777:Anesthetics; D001463:Barbiturates; D018696:Neuroprotective Agents; D002245:Carbon Dioxide; D014978:Xenon; D020927:Dexmedetomidine; D007649:Ketamine; D007530:Isoflurane; D009609:Nitrous Oxide; D006221:Halothane; D015742:Propofol
Anesthesiology. 2004 Oct;101(4):912-7
15448524
Anesthesiology. 2008 Mar;108(3):457-66
18292683
Anesth Analg. 2005 Jan;100(1):215-225
15616081
Can J Anaesth. 2006 Feb;53(2):194-201
16434762
Anesthesiology. 2006 Jan;104(1):80-9
16394694
Lab Anim. 2002 Apr;36(2):127-33
11943076
J Cereb Blood Flow Metab. 2006 Feb;26(2):199-208
16034370
Anesth Analg. 2003 Feb;96(2):524-31, table of contents
12538207
Anesth Analg. 2006 Feb;102(2):456-61
16428542
Anesthesiology. 1984 Jun;60(6):575-9
6731913
Brain Res. 2005 Aug 30;1054(2):143-51
16081051
Curr Opin Anaesthesiol. 2005 Aug;18(4):405-11
16534266
Curr Opin Anaesthesiol. 2005 Jun;18(3):293-7
16534354
Neuroendocrinology. 1996 Feb;63(2):166-72
9053781
Nat Med. 1998 Apr;4(4):460-3
9546794
Anesthesiology. 2009 May;110(5):1077-85
19352168
Anesthesiology. 2004 Jul;101(1):75-81
15220774
Anesth Analg. 2003 Aug;97(2):564-571
12873954
Anesthesiology. 2005 Nov;103(5):969-77
16249671
Stroke. 2001 Aug;32(8):1920-5
11486126
Br Med Bull. 2005 Jan 31;71:77-92
15684247
Brain Res. 1995 Feb 27;673(1):112-8
7757462
Anesthesiology. 2005 Aug;103(2):318-26
16052114
Brain Res. 2001 Sep 21;913(2):185-9
11549385
J Cereb Blood Flow Metab. 2003 Oct;23(10):1168-73
14526227
Anesthesiology. 2005 Sep;103(3):532-9
16129978
CNS Drug Rev. 2007 Fall;13(3):333-51
17894649
Br J Anaesth. 2006 Oct;97(4):517-24
16928698
Neurosci Lett. 2007 Sep 20;425(1):59-62
17723266
Forensic Sci Int. 2001 Dec 27;124(2-3):235-6
11792520
Yonsei Med J. 1993 Jun;34(2):152-7
8379194
Anesthesiology. 1996 Jun;84(6):1475-84
8669689
Indian J Physiol Pharmacol. 1981 Jul-Sep;25(3):289-91
7298156
Lab Anim. 2000 Jan;34(1):91-6
10759372
Crit Care Med. 2000 Jun;28(6):1899-904
10890639
Anesth Analg. 2005 Aug;101(2):524-534
16037171
Anesthesiology. 2000 May;92(5):1335-42
10781279
J Neurosci Res. 2002 May 1;68(3):352-62
12111866
Brain Res Brain Res Protoc. 1999 Dec;4(3):295-302
10592338
Lab Anim. 2003 Jul;37(3):241-8
12869287
Anesthesiology. 2005 Mar;102(3):606-15
15731600
Biochemistry. 2006 Sep 26;45(38):11632-41
16981722
Brain Res. 2008 Dec 15;1245:26-35
18930717
Anesthesiology. 2007 Nov;107(5):756-67
18073551
Toxicol Appl Pharmacol. 2006 Jan 1;210(1-2):100-7
16307766
Life Sci. 2007 Mar 6;80(13):1157-75
17258776
Anesthesiology. 2000 May;92(5):1343-9
10781280
Contemp Top Lab Anim Sci. 2003 Jan;42(1):19-27
12580570
Brain Res. 1988 Jun 14;452(1-2):329-35
3401739
Curr Opin Anaesthesiol. 2006 Oct;19(5):481-6
16960478
Neuroscience. 2005;132(4):967-77
15857702
Neurosci Lett. 1991 Jul 22;128(2):297-300
1945051
Anesth Analg. 2004 Mar;98(3):798-805, table of contents
14980940
Anesthesiology. 1993 Aug;79(2):306-12
8102042
Anesthesiology. 2003 Oct;99(4):876-81
14508320
Anesthesiology. 1983 Jun;58(6):533-9
6859583
Med Toxicol. 1986 Sep-Oct;1(5):362-74
3537624
Stroke. 2002 Jul;33(7):1889-98
12105371
Curr Opin Anaesthesiol. 2006 Aug;19(4):382-4
16829718
Br J Anaesth. 1996 Oct;77(4):441-4
8942324
Anesthesiology. 2004 Sep;101(3):695-703
15329594
Toxicol Sci. 2006 May;91(1):192-201
16500925
J Cardiothorac Vasc Anesth. 2010 Feb;24(1):131-42
19640746
J Neurosurg Anesthesiol. 2005 Jan;17(1):20-6
15632538
J Anesth. 2005;19(2):150-6
15875133