TY - JOUR
T1 - Anesthetic and subanesthetic doses of isoflurane conditioning provides strong protection against delayed cerebral ischemia in a mouse model of subarachnoid hemorrhage
AU - Athiraman, Umeshkumar
AU - Liu, Meizi
AU - Jayaraman, Keshav
AU - Yuan, Jane
AU - Mehla, Jogender
AU - Zipfel, Gregory J.
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Delayed cerebral ischemia (DCI) is identified as one of the significant contributors to poor patient outcome after aneurysmal subarachnoid hemorrhage (SAH). We previously reported that a supratherapeutic dose of isoflurane conditioning (2%) provided robust protection against SAH-induced DCI. The aim of our current study is to compare the efficacy of the supratherapeutic dose of isoflurane to that typically used to establish general anesthesia or sedation. After IRB approval for animal studies, ten to fourteen-week-old wild-type male mice (C57BL/6) were divided into five groups – sham, SAH alone, or SAH with isoflurane conditioning (0.5%, 1%, and 2%). Conditioning was performed with one-hour of isoflurane initiated one-hour after induction of SAH via endovascular perforation technique. Vasospasm measurement in the middle cerebral artery was assessed 72 h after SAH. Neurological assessment was performed at baseline and for next three days after SAH. It was identified that all tested doses of isoflurane conditioning (0.5%, 1%, and 2%) significantly attenuated large artery vasospasm and markedly improved neurological deficits following SAH. No significant differences in neurovascular outcome were noted between the three doses of isoflurane conditioning. Our data show that isoflurane dosing typically used for general anesthesia (1%) or sedation (0.5%) provide similar levels of DCI protection in SAH as that provided by a supratherapeutic dose (2%). This result has important implications for future translational studies. Additional studies examining the therapeutic potential of anesthetic conditioning for SAH are therefore warranted.
AB - Delayed cerebral ischemia (DCI) is identified as one of the significant contributors to poor patient outcome after aneurysmal subarachnoid hemorrhage (SAH). We previously reported that a supratherapeutic dose of isoflurane conditioning (2%) provided robust protection against SAH-induced DCI. The aim of our current study is to compare the efficacy of the supratherapeutic dose of isoflurane to that typically used to establish general anesthesia or sedation. After IRB approval for animal studies, ten to fourteen-week-old wild-type male mice (C57BL/6) were divided into five groups – sham, SAH alone, or SAH with isoflurane conditioning (0.5%, 1%, and 2%). Conditioning was performed with one-hour of isoflurane initiated one-hour after induction of SAH via endovascular perforation technique. Vasospasm measurement in the middle cerebral artery was assessed 72 h after SAH. Neurological assessment was performed at baseline and for next three days after SAH. It was identified that all tested doses of isoflurane conditioning (0.5%, 1%, and 2%) significantly attenuated large artery vasospasm and markedly improved neurological deficits following SAH. No significant differences in neurovascular outcome were noted between the three doses of isoflurane conditioning. Our data show that isoflurane dosing typically used for general anesthesia (1%) or sedation (0.5%) provide similar levels of DCI protection in SAH as that provided by a supratherapeutic dose (2%). This result has important implications for future translational studies. Additional studies examining the therapeutic potential of anesthetic conditioning for SAH are therefore warranted.
KW - Aneurysmal subarachnoid hemorrhage
KW - DCI
KW - Isoflurane concentration
KW - Neurologic outcome
UR - http://www.scopus.com/inward/record.url?scp=85094135871&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2020.147169
DO - 10.1016/j.brainres.2020.147169
M3 - Article
C2 - 33132166
AN - SCOPUS:85094135871
SN - 0006-8993
VL - 1750
JO - Brain Research
JF - Brain Research
M1 - 147169
ER -