Saeid Taheri1, Anandakumar Shunmugavel2, Danielle Clark2, Honglian Shi3. 1. Department of Neurosciences, Medical University of South Carolina, Charleston, SC, 29425. Electronic address: taheri@musc.edu. 2. Department of Pediatrics,Medical University of South Carolina, Charleston, SC, 29425. 3. Department of Pharmacology & Toxicology, University of Kansas, Lawrence, KS, 66045.
Abstract
BACKGROUND: Recent studies show neuroprotective benefits of isoflurane (ISO) administered during cerebral ischemia. However, the available studies evaluated cerebral injury only at a single time point following the intervention and thus the longitudinal effect of ISO on ischemic tissues remains to be investigated. OBJECTIVE: The objective of the present study was to investigate the longitudinal effect of ISO treatment in counteracting the deleterious effect of ischemia by evoking the transcription factor, hypoxia inducible factor-1 (HIF-1), and vascular endothelial growth factor (VEGF). METHODS: Focal cerebral ischemia was induced in 70 rats by filament medial cerebral artery occlusion (MCAo) method. MCAo rats were randomly assigned to control (90 min ischemia) and MCAo+ISO (90 min ischemia+2% ISO) groups. Infarct volume, edema, intracerebral hemorrhage (ICH), and regional cerebral blood flow (rCBF) were measured in eight in vivo sequential MR imaging sessions for 3 weeks. Western blot analysis and immunofluorescence were used to determine the expression level of HIF-1α (the regulatable subunit of HIF-1) and VEGF proteins. RESULTS: ISO inhalation during ischemia significantly decreased the surge of infarct volume, edema, ICH, and reduced the mortality rate (p<0.01). ISO transiently altered the rCBF, significantly enhanced the expression of HIF-1α and VEGF, and decreased the immune cell infiltration. Locomotor dysfunction was ameliorated at a significantly faster pace, and the benefit was seen to persist up to three weeks. CONCLUSION: Treatment with ISO during ischemia limits the deadly surge in the dynamics of ischemia reperfusion injury with no observed long-term inverse effect.
BACKGROUND: Recent studies show neuroprotective benefits of isoflurane (ISO) administered during cerebral ischemia. However, the available studies evaluated cerebral injury only at a single time point following the intervention and thus the longitudinal effect of ISO on ischemic tissues remains to be investigated. OBJECTIVE: The objective of the present study was to investigate the longitudinal effect of ISO treatment in counteracting the deleterious effect of ischemia by evoking the transcription factor, hypoxia inducible factor-1 (HIF-1), and vascular endothelial growth factor (VEGF). METHODS: Focal cerebral ischemia was induced in 70 rats by filament medial cerebral artery occlusion (MCAo) method. MCAo rats were randomly assigned to control (90 min ischemia) and MCAo+ISO (90 min ischemia+2% ISO) groups. Infarct volume, edema, intracerebral hemorrhage (ICH), and regional cerebral blood flow (rCBF) were measured in eight in vivo sequential MR imaging sessions for 3 weeks. Western blot analysis and immunofluorescence were used to determine the expression level of HIF-1α (the regulatable subunit of HIF-1) and VEGF proteins. RESULTS:ISO inhalation during ischemia significantly decreased the surge of infarct volume, edema, ICH, and reduced the mortality rate (p<0.01). ISO transiently altered the rCBF, significantly enhanced the expression of HIF-1α and VEGF, and decreased the immune cell infiltration. Locomotor dysfunction was ameliorated at a significantly faster pace, and the benefit was seen to persist up to three weeks. CONCLUSION: Treatment with ISO during ischemia limits the deadly surge in the dynamics of ischemia reperfusion injury with no observed long-term inverse effect.
Authors: Ilya L Gubskiy; Daria D Namestnikova; Elvira A Cherkashova; Vladimir P Chekhonin; Vladimir P Baklaushev; Leonid V Gubsky; Konstantin N Yarygin Journal: Transl Stroke Res Date: 2017-11-25 Impact factor: 6.829
Authors: Michael S Dittmar; Walter Petermichl; Regina Lindner; Barbara Sinner; Bernhard M Graf; Felix Schlachetzki; Michael Gruber Journal: PLoS One Date: 2015-06-19 Impact factor: 3.240
Authors: Yirong Yang; Lisa Y Yang; Lilla Orban; Darnell Cuylear; Jeffrey Thompson; Bruce Simon; Yi Yang Journal: Brain Stimul Date: 2018-02-15 Impact factor: 8.955
Authors: Line Fuglsang Hansen; Nicholine S K Nielsen; Laura Cathrine Christoffersen; Christina Kruuse Journal: Ann Clin Transl Neurol Date: 2021-06-16 Impact factor: 4.511