台北榮民總醫院醫院評鑑 臺北榮民總醫院耳鼻喉頭頸醫學部 Taipei Veterans General Hospital

Presentation on theme: "台北榮民總醫院醫院評鑑 臺北榮民總醫院耳鼻喉頭頸醫學部 Taipei Veterans General Hospital"— Presentation transcript:

1 台北榮民總醫院醫院評鑑 臺北榮民總醫院耳鼻喉頭頸醫學部 Taipei Veterans General Hospital Otorhinolaryngology-Head & Neck Surgery Soluble Epoxide Hydrolase Inhibition Modulates Gene Expression of Antioxidant Enzymes in Olfactory Bulb after Ischemic Stroke 葉建甫 林永煬 臺北榮民總醫院 耳鼻喉頭頸醫學部 鼻頭頸科 國立陽明大學耳鼻喉科 臺北榮民總醫院 重症醫學部 1

2 Olfactory dysfunction & ischemic stroke
Introduction Olfactory dysfunction & ischemic stroke Cause Head trauma URI CRS Neurological diseases After ischemic stroke 28.2% hyposmia 15.4% anosmia Murphy, C., et al., JAMA, (2002) 288: Wehling et al. BMC Neurology (2015) 15:199

3 Olfactory dysfunction & ischemic stroke
Introduction Olfactory dysfunction & ischemic stroke In tMCAO mice, microglial activation was first seen in the OB and then the ischemic lesion. Excessive microglial activation aggravates olfactory dysfunction. Ischemic stroke → olfactory dysfunction Brain 2009: 132; 940–954 Biochimica et Biophysica Acta 1842 (2014) 2193–2203

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5 Neuroinflammation: activation of microglia
Inflammation leads to activation of microglia, the brain’s resident immune cells. (Masahito Kawabori et al., 2015) (Lee, et al., 2014)

6 Olfactory dysfunction
Introduction Olfactory dysfunction

7 Neuroinflammation: role of sEH
Introduction Neuroinflammation: role of sEH Inhibition of soluble epoxide hydrolase (sEH) in MCAO rats induces a neuroprotective phenotype in activated microglia and increases antioxidant. (Yeh, et al., unpublished) Anti-oxidant sEH

8 Animal model MCAO AUDA (sEH inhibitor) Control Materials & Methods
Wistar-Kyoto (WKY) rat, male, 10wk, g Middle cerebral artery occlusion (MCAO) Intraperitoneal injection Expose bil. CCA→ MCAO → 90 min bil. CCAO MCAO AUDA (sEH inhibitor) 20 mg/kg Control

9 Behavioral test Materials & Methods 1 days after MCAO
Buried food finding test 統計資料 eNeuro 5 June 2017, 4 (3)

10 Reverse Transcription Quantitative Polymerase Chain Reaction (PCR)
Materials & Methods Reverse Transcription Quantitative Polymerase Chain Reaction (PCR) 3 days after MCAO; Zoletil/Xylazine Total RNA extraction from ischemic cortex Reverse-transcribed to cDNA Reverse transcription quantitative PCR

11 Olfactory function test - Buried food finding test
台北榮民總醫院醫院評鑑 Results Olfactory function test - Buried food finding test

12 sEH Inhibitor attenuated M1 microglia expression
台北榮民總醫院醫院評鑑 Results sEH Inhibitor attenuated M1 microglia expression

13 Heme oxygenase-1 (HO-1), increased after sEH inhibitor administration
台北榮民總醫院醫院評鑑 Results Heme oxygenase-1 (HO-1), increased after sEH inhibitor administration HO-1

14 Olfactory marker protein (OMP)
台北榮民總醫院醫院評鑑 Results Olfactory marker protein (OMP) OMP: a marker of olfactory sensory neuron

15 After ischemic stroke Olfactory dysfunction M1 microglia activation
台北榮民總醫院醫院評鑑 Discussion After ischemic stroke Olfactory dysfunction M1 microglia activation Increase proinflammatory cytokine ↓ antioxidant HO-1 ↓ OMP

16 After sEH inhibitor administration
台北榮民總醫院醫院評鑑 Discussion After sEH inhibitor administration M1 microglia activation decreased ↓ antioxidant HO-1 increased ↓ OMP improved

17 台北榮民總醫院醫院評鑑 Discussion In the future Protein measurement

18 台北榮民總醫院醫院評鑑 Conclusion Soluble epoxide hydrolase inhibition modulates gene expression of antioxidant enzymes in olfactory bulb after ischemic stroke

19 台北榮民總醫院醫院評鑑 葉建甫醫師 臺北榮民總醫院 鼻頭頸科 主治醫師 陽明大學醫學系 講師 放個圖