Isoflurane posttreatment reduces brain injury after an intracerebral hemorrhagic stroke in mice

Nikan H. Khatibi, Qingyi Ma, William Rolland, Robert Ostrowski, Nancy Fathali, Robert Martin, Richard Lee Applegate, Gary Stier, Jiping Tang, John H. Zhang

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating stroke subtype affecting 120,000 Americans annually. Of those affected, 40%to 50% will die within the first 30 days, whereas the survivors are left with a lifetime of neurobehavioral disabilities. Recently, it has been shown that volatile anesthetics such as isoflurane can reduce brain injury after an ischemic stroke. As a result, in this study, we investigated the effects of isoflurane as a posttreatment therapeutic modality in ICH-injured mice. Specifically, we investigated whether isoflurane posttreatment can preserve the structural integrity of the brain by reducing apoptotic damage and, in turn, improve functional outcome by amelioration of brain edema and neurobehavioral deficits. METHODS: Male CD1 mice (n = 53) were divided into the following groups: sham (n = 14), ICH (n = 14), ICH treated with 1.5% isoflurane posttreatment for 1 hour (n = 15), and ICH treated with 1.5% isoflurane posttreatment for 2 hours (n = 10). The blood injection ICH model was adapted; this involved extracting autologous blood from the mouse tail and injecting it directly into the right basal ganglia. One hour after surgery, treated mice were placed in a glass chamber maintained at 37°C and infused with 1.5% isoflurane for 1 or 2 hours. At 24 hours postinjury, mice were assessed for neurobehavioral deficits using the Modified Garcia Score and then killed and assessed for brain water content. Double immunofluorescent staining was performed using neuronal marker MAP-2 and TUNEL under a fluorescent microscope to assess for apoptosis. RESULTS: Our results indicated that after 1-hour 1.5% isoflurane posttreatment, there was a significant reduction in brain edema, a decrease in apoptotic cell death, and a significant improvement in neurobehavioral deficits. CONCLUSIONS: Our results suggest that isoflurane may be an effective posttreatment therapeutic option for ICH because of its ability to reduce structural damage and subsequently preserve functional integrity.

Original languageEnglish (US)
Pages (from-to)343-348
Number of pages6
JournalAnesthesia and Analgesia
Volume113
Issue number2
DOIs
StatePublished - Aug 2011
Externally publishedYes

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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    Khatibi, N. H., Ma, Q., Rolland, W., Ostrowski, R., Fathali, N., Martin, R., Applegate, R. L., Stier, G., Tang, J., & Zhang, J. H. (2011). Isoflurane posttreatment reduces brain injury after an intracerebral hemorrhagic stroke in mice. Anesthesia and Analgesia, 113(2), 343-348. https://doi.org/10.1213/ANE.0b013e31821f9524