PMID- 37189781
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230519
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 11
IP  - 4
DP  - 2023 Apr 12
TI  - Isoflurane Conditioning Provides Protection against Subarachnoid Hemorrhage 
      Induced Delayed Cerebral Ischemia through NF-kB Inhibition.
LID - 10.3390/biomedicines11041163 [doi]
LID - 1163
AB  - Delayed cerebral ischemia (DCI) is the largest treatable cause of poor outcome 
      after aneurysmal subarachnoid hemorrhage (SAH). Nuclear Factor 
      Kappa-light-chain-enhancer of Activated B cells (NF-kB), a transcription factor 
      known to function as a pivotal mediator of inflammation, is upregulated in SAH 
      and is pathologically associated with vasospasm. We previously showed that a 
      brief exposure to isoflurane, an inhalational anesthetic, provided multifaceted 
      protection against DCI after SAH. The aim of our current study is to investigate 
      the role of NF-kB in isoflurane-conditioning-induced neurovascular protection 
      against SAH-induced DCI. Twelve-week-old wild type male mice (C57BL/6) were 
      divided into five groups: sham, SAH, SAH + Pyrrolidine dithiocarbamate (PDTC, a 
      selective NF-kB inhibitor), SAH + isoflurane conditioning, and SAH + PDTC with 
      isoflurane conditioning. Experimental SAH was performed via endovascular 
      perforation. Anesthetic conditioning was performed with isoflurane 2% for 1 h, 1 
      h after SAH. Three doses of PDTC (100 mg/kg) were injected intraperitoneally. 
      NF-kB and microglial activation and the cellular source of NF-kB after SAH were 
      assessed by immunofluorescence staining. Vasospasm, microvessel thrombosis, and 
      neuroscore were assessed. NF-kB was activated after SAH; it was attenuated by 
      isoflurane conditioning. Microglia was activated and found to be a major source 
      of NF-kB expression after SAH. Isoflurane conditioning attenuated microglial 
      activation and NF-kB expression in microglia after SAH. Isoflurane conditioning 
      and PDTC individually attenuated large artery vasospasm and microvessel 
      thrombosis, leading to improved neurological deficits after SAH. The addition of 
      isoflurane to the PDTC group did not provide any additional DCI protection. These 
      data indicate isoflurane-conditioning-induced DCI protection after SAH is 
      mediated, at least in part, via downregulating the NF-kB pathway.
FAU - Liu, Meizi
AU  - Liu M
AUID- ORCID: 0000-0002-7633-3384
AD  - Department of Anesthesiology, Department of Neurosurgery, Washington University 
      in St. Louis, St. Louis, MO 63110, USA.
FAU - Jayaraman, Keshav
AU  - Jayaraman K
AUID- ORCID: 0000-0002-5227-7023
AD  - Department of Anesthesiology, Department of Neurosurgery, Washington University 
      in St. Louis, St. Louis, MO 63110, USA.
FAU - Mehla, Jogender
AU  - Mehla J
AD  - Department of Anesthesiology, Department of Neurosurgery, Washington University 
      in St. Louis, St. Louis, MO 63110, USA.
FAU - Diwan, Deepti
AU  - Diwan D
AD  - Department of Anesthesiology, Department of Neurosurgery, Washington University 
      in St. Louis, St. Louis, MO 63110, USA.
FAU - Nelson, James W
AU  - Nelson JW
AD  - Department of Anesthesiology, Department of Neurosurgery, Washington University 
      in St. Louis, St. Louis, MO 63110, USA.
FAU - Hussein, Ahmed E
AU  - Hussein AE
AD  - Department of Anesthesiology, Department of Neurosurgery, Washington University 
      in St. Louis, St. Louis, MO 63110, USA.
FAU - Vellimana, Ananth K
AU  - Vellimana AK
AD  - Department of Anesthesiology, Department of Neurosurgery, Washington University 
      in St. Louis, St. Louis, MO 63110, USA.
FAU - Abu-Amer, Yousef
AU  - Abu-Amer Y
AD  - Department of Orthopedic Surgery and Cell Biology & Physiology, Shriners Hospital 
      for Children, Washington University School of Medicine, St. Louis, MO 63110, USA.
FAU - Zipfel, Gregory J
AU  - Zipfel GJ
AD  - Department of Anesthesiology, Department of Neurosurgery, Washington University 
      in St. Louis, St. Louis, MO 63110, USA.
FAU - Athiraman, Umeshkumar
AU  - Athiraman U
AUID- ORCID: 0000-0002-9086-0607
AD  - Department of Anesthesiology, Department of Neurosurgery, Washington University 
      in St. Louis, St. Louis, MO 63110, USA.
LA  - eng
GR  - K08NS125038/NH/NIH HHS/United States
GR  - NS091603/NH/NIH HHS/United States
PT  - Journal Article
DEP - 20230412
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC10135581
OTO - NOTNLM
OT  - NF-kB
OT  - aneurysmal subarachnoid hemorrhage
OT  - delayed cerebral ischemia
OT  - isoflurane
OT  - neuroprotection
COIS- The authors declare no conflict of interest.
EDAT- 2023/05/16 06:42
MHDA- 2023/05/16 06:43
PMCR- 2023/04/12
CRDT- 2023/05/16 01:11
PHST- 2023/02/27 00:00 [received]
PHST- 2023/04/08 00:00 [revised]
PHST- 2023/04/11 00:00 [accepted]
PHST- 2023/05/16 06:43 [medline]
PHST- 2023/05/16 06:42 [pubmed]
PHST- 2023/05/16 01:11 [entrez]
PHST- 2023/04/12 00:00 [pmc-release]
AID - biomedicines11041163 [pii]
AID - biomedicines-11-01163 [pii]
AID - 10.3390/biomedicines11041163 [doi]
PST - epublish
SO  - Biomedicines. 2023 Apr 12;11(4):1163. doi: 10.3390/biomedicines11041163.