Xiaofang Li1, Likai Su1, Xiangjian Zhang2,3, Cong Zhang2,3, Lina Wang2,3, Yaoru Li2,3, Ye Zhang2,3, Tingting He2,3, Xingyuan Zhu2,3, Lili Cui2,3. 1. a Department of Neurology , Affiliated Hospital of Hebei University , Baoding , PR China. 2. b Department of Neurology , Second Hospital of Hebei Medical University , Shijiazhuang , China. 3. c Hebei Key Laboratory for Neurology , Second Hospital of Hebei Medical University , Shijiazhuang , PR China.
Abstract
BACKGROUND: Inflammatory damage plays an important role in ischemic stroke and provides potential targets for therapy. Ulinastatin (UTI), a drug used to treat shock and acute pancreatitis in clinic, has attracted attention for its protective effects through immunomodulatory and anti-inflammatory properties. However, the effect of UTI in the acute phase of cerebral ischemia/reperfusion (I/R) is not clear. This study is to investigate the potential neuroprotective effect of UTI and explore its underlying mechanisms. METHODS: Male CD-1 mice were subjected to transient middle cerebral artery occlusion (tMCAO) and randomly assigned into four groups: Sham (sham-operated) group, tMCAO (tMCAO + 0.9% saline) group, UTI-L (tMCAO + UTI 1500 U/100 g), and UTI-H (tMCAO + UTI 3000 U/100 g) group. UTI was administered immediately after reperfusion in the UTI-L and UTI-H groups. About 24 h after the reperfusion, the neurological deficit, brain water content, and infarct volume were detected. Immunohistochemistry, western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to detect the expression of TLR4 and NF-κB in the ischemic cerebral cortex. RESULTS: Compared with tMCAO group, both UTI-L and UTI-H groups dramatically ameliorated neurological deficit (p < 0.05), lessened the brain water content (p < 0.05) and infarct volume (p < 0.05), and decreased the expression of TLR4 and NF-κB. CONCLUSION: These results showed that UTI protected the brain against ischemic injury which may be due to the alleviation of inflammation reaction in early stage through downregulating TLR4 and NF-κB expression.
BACKGROUND: Inflammatory damage plays an important role in ischemic stroke and provides potential targets for therapy. Ulinastatin (UTI), a drug used to treat shock and acute pancreatitis in clinic, has attracted attention for its protective effects through immunomodulatory and anti-inflammatory properties. However, the effect of UTI in the acute phase of cerebral ischemia/reperfusion (I/R) is not clear. This study is to investigate the potential neuroprotective effect of UTI and explore its underlying mechanisms. METHODS: Male CD-1 mice were subjected to transient middle cerebral artery occlusion (tMCAO) and randomly assigned into four groups: Sham (sham-operated) group, tMCAO (tMCAO + 0.9% saline) group, UTI-L (tMCAO + UTI 1500 U/100 g), and UTI-H (tMCAO + UTI 3000 U/100 g) group. UTI was administered immediately after reperfusion in the UTI-L and UTI-H groups. About 24 h after the reperfusion, the neurological deficit, brain water content, and infarct volume were detected. Immunohistochemistry, western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to detect the expression of TLR4 and NF-κB in the ischemic cerebral cortex. RESULTS: Compared with tMCAO group, both UTI-L and UTI-H groups dramatically ameliorated neurological deficit (p < 0.05), lessened the brain water content (p < 0.05) and infarct volume (p < 0.05), and decreased the expression of TLR4 and NF-κB. CONCLUSION: These results showed that UTI protected the brain against ischemic injury which may be due to the alleviation of inflammation reaction in early stage through downregulating TLR4 and NF-κB expression.
Authors: Ying Chen; Zhipeng Xu; Qi Song; Zhenjie Wang; Zhong Ji; Zhaolei Qiu; Feng Cheng; Hai Jiang Journal: Nan Fang Yi Ke Da Xue Xue Bao Date: 2019-10-30
Authors: Xiaodi Chen; Sakura Nakada; John E Donahue; Ray H Chen; Richard Tucker; Joseph Qiu; Yow-Pin Lim; Edward G Stopa; Barbara S Stonestreet Journal: Exp Neurol Date: 2019-03-23 Impact factor: 5.330
Authors: Jaini J Paltian; Angélica S Dos Reis; Amanda W S Martins; Eduardo B Blödorn; Eduardo N Dellagostin; Liane K Soares; Ricardo F Schumacher; Vinícius F Campos; Diego Alves; Cristiane Luchese; Ethel Antunes Wilhelm Journal: Mol Neurobiol Date: 2022-08-15 Impact factor: 5.682
Authors: Koteswara Rao Nalamolu; Siva Reddy Challa; Casimir A Fornal; Natalia A Grudzien; Laura C Jorgenson; Mouneeb M Choudry; Nathan J Smith; Cassandra J Palmer; David M Pinson; Jeffrey D Klopfenstein; Krishna Kumar Veeravalli Journal: Transl Stroke Res Date: 2021-01-11 Impact factor: 6.800