1.Correlation between plasma cathepsin L and collateral circulation in acute ischemic stroke patients with cerebral artery stenosis
Bo ZHAO ; Yuechun LI ; Xiwa HAO ; Changchun JIANG
International Journal of Cerebrovascular Diseases 2017;25(1):44-48
Objective To investigate the correlation between plasma cathepsin L (CatL) levels and establishment of cerebral collateral circulation in acute ischemic stroke patients with cerebral artery stenosis.Methods The patients with acute ischemic stroke with at least one cerebral large artery (including internal carotid artery,middle cerebral artery,vertebral artery,and basilar artery) stenosis > 70% diagnosed by whole cerebral angiography were enrolled.ASITN/SIR blood flow classification system was used to systematically evaluate the establishment of cerebral collateral circulation.Grade 0-2 was defined as poor collateral branch and 3-4 was defined as good collateral branch,Enzyme linked immunosorbent assay was used to detect the plasma CatL level.Results A total of 79 acute ischemic stroke patients with cerebral artery stenosis were enrolled,including 63 male and 16 female.Their mean age was 58.76 ± 12.24 years old.There were 51 patients (64.56%) in the poor collateral branch group and 28 (35.44%) in the good collateral branch group.There was no significant difference in plasma CatL levels between the good collateral circulation group and the poor collateral circulation group (7.09± 2.27 mg/L vs.8.79±3.53 mg/L;t =2.751,P =0.069).Multivariable logistic regression analysis showed that only the high National Institutes of Health Stroke Scale score was the independent risk factor for poor collateral circulation (odds ratio 0.935,95% confidence interval 0.823-0.963;P=0.046),and there was no significant independent correlation between plasma CatL levels and collateral circulation (odds ratio 0.910,95% confidence interval 0.766-1.081;P =0.285).Conclusion There was no significant correlation between plasma CatL levels and cerebral collateral development in acute ischemic stroke patients with cerebral artery stenosis.
2.Long-term butylphthalide pretreatment attenuates ischemic brain injury in mice with permanent distal middle cerebral artery occlusion through Nrf2 pathway
Mingying SUN ; Chao CHEN ; Yuechun LI ; Baojun WANG ; Xiwa HAO ; Jiangxia PANG ; Changchun JIANG
International Journal of Cerebrovascular Diseases 2021;29(3):194-200
Objective:To investigate the neuroprotective effect of long-term prophylactic use of buphthalein on mice with permanent distal middle cerebral artery occlusion and its relationship with the nuclear factor erysid 2 related factor 2 (Nrf2) pathway.Methods:Nrf2 + /+ wild-type and Nrf2 -/- knockout mice were randomly divided into control group (equal volume vegetable oil), low-dose butylphthalide group (20 mg/kg) and high-dose butylphthalide group (60 mg/kg), with 6 mice in each group. The drug was administered once a day by gavage for 1 month, and then a permanent middle cerebral artery occlusion model was induced by electrocoagulation. After the model was made, the drug was continued and the mice were sacrificed on the 10 th day. The modified Longa grading scale and the rotating rod test were used to evaluate neurological deficits on the 3 rd and 10 th day after the model was made. After the mice were sacrificed, the cerebral infarct volume was measured by triphenyltetrazolium chloride staining. The brain water content was measured by dry and wet weight method. The expression of Nrf2 pathway related factors, including Nrf2, heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1) were measured by quantitative real-time PCR and Western blotting. Results:On the 10 th day after modeling, compared with the Nrf2 -/- control group, the neurological deficit was significantly milder, the volume of cerebral infarction and brain water content were significantly smaller, and the mRNA and protein levels of Nrf2, HO-1 and NQO1 were significantly higher in the Nrf2 + /+ control group, and the differences were statistically significant ( P<0.05). For Nrf2 + /+ mice, compared with the control group, the cerebral infarct volume was significantly reduced ( P<0.05), the brain water content was significantly reduced ( P<0.05), and the neurological function recovery was significantly better ( P<0.05), and the levels of Nrf2, HO-1, and NQO1 mRNA and protein were significantly higher in the high-dose butylphthalide group (all P<0.05). For Nrf2 -/- mice, there were no significant differences in neurological function, cerebral infarction group volume, brain water content, Nrf2, HO-1, NQO1 mRNA and protein levels among the groups. Conclusion:Long-term butylphthalide pretreatment can significantly improve the neurological function, reduce cerebral infarction volume, reduce brain water content, and increase Nrf2, HO-1, NQO1 mRNA and protein expression levels in mice with permanent distal middle cerebral artery occlusion, suggesting butylphthalide may play a neuroprotective effect by up-regulating the expression of Nrf2 gene and its downstream antioxidant stress factors HO-1 and NQO1.
3.Associations of serum low-density lipoprotein cholesterol with hematoma enlargement, early neurological deterioration, and outcome in patients with acute spontaneous intracerebral hemorrhage
Ting LAN ; Xiwa HAO ; Lin LYU ; Cuiqin ZHANG ; Hongmei QIAO ; Bobo ZHANG ; Yongming CHEN ; Qidi BO ; Meiyou YAN ; Hui LYU ; Jingfen ZHANG
International Journal of Cerebrovascular Diseases 2024;32(7):506-511
Objective:To investigate associations of serum low-density lipoprotein cholesterol (LDL-C) with hematoma enlargement, early neurological deterioration (END), and outcome in patients with acute spontaneous intracerebral hemorrhage (ICH).Methods:"A multi-center registration study for spontaneous intracerebral hemorrhage in Inner Mongolia" (registration number: ChiCTR2000029494) database was used to include patients with ICH who completed their first head CT scan within 6 hours after onset, underwent blood lipid examination, CT follow-up within 24 hours of onset, and accurately measured hematoma volume using 3D Slicer software between June 2020 and September 2022. HE was defined as hematoma volume increasing >33% or >6 ml at 24 hours, or ventricular hematoma volume increasing ≥1 ml compared to the baseline. END was defined as an increase of ≥4 in the National Institutes of Health Stroke Scale (NIHSS) score from the baseline or death within 24 hours after onset. The follow-up was conducted at 3 months after onset, and the modified Rankin Scale score >2 was defined as poor outcome. Multivariate logistic analysis was used to determine the independent correlation between LDL-C and HE, END, and outcome. Results:A total of 338 patients with ICH were enrolled, including 206 males (60.9%). LDL-C was 2.39±1.22 mmol/L. Eighty-eight patients (26.0%) developed HE, 67 (19.8%) developed END, and 162 (47.9%) had poor outcome at 3 months. Multivariate logistic analysis showed that after adjusting for confounding factors, there was a significant independent negative correlation between LDL-C and HE (odds ratio 0.312, 95% confidence interval 0.208-0.467; P<0.001) and END (odds ratio 0.408, 95% confidence interval 0.275-0.606; P<0.001), but not with the outcome at 3 months. Conclusion:Lower LDL-C is associated with HE and END in patients with ICH, but not with the outcome.