OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

OBJECTIVE: To explore the mechanism that mediates the effect of soybean isoflavones (SI) against cerebral ischemia/reperfusion (I/R) injury in light of the regulation of regional cerebral blood flow (rCBF), ferroptosis, inflammatory response and blood-brain barrier (BBB) permeability. METHODS: A total of 120 male SD rats were equally randomized into sham-operated group (Sham group), cerebral I/R injury group and SI pretreatment group (SI group). Focal cerebral I/R injury was induced in the latter two groups using a modified monofilament occlusion technique, and the intraoperative changes of real-time cerebral cortex blood flow were monitored using a laser Doppler flowmeter (LDF). The postoperative changes of cerebral pathological morphology and the ultrastructure of the neurons and the BBB were observed with optical and transmission electron microscopy. The neurological deficits of the rats was assessed, and the severities of cerebral infarction, brain edema and BBB disruption were quantified. The contents of Fe²⁺, GSH, MDA and MPO in the ischemic penumbra were determined with spectrophotometric tests. Serum levels of TNF-α and IL-1βwere analyzed using ELISA, and the expressions of GPX4, MMP-9 and occludin around the lesion were detected with Western blotting and immunohistochemistry. RESULTS: The rCBF was sharply reduced in the rats in I/R group and SI group after successful insertion of the monofilament. Compared with those in Sham group, the rats in I/R group showed significantly increased neurological deficit scores, cerebral infarction volume, brain water content and Evans blue permeability (P < 0.01), decreased Fe²⁺ level, increased MDA level, decreased GSH content and GPX4 expression (P < 0.01), increased MPO content and serum levels of TNF-α and IL-1β (P < 0.01), increased MMP-9 expression and lowered occludin expression (P < 0.01). All these changes were significantly ameliorated in rats pretreated with IS prior to I/R injury (P < 0.05 or 0.01). CONCLUSION SI preconditioning reduces cerebral I/R injury in rats possibly by improving rCBF, inhibiting ferroptosis and inflammatory response and protecting the BBB.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Matrix Metalloproteinase 9/metabolism* ; Soybeans/metabolism* ; Occludin/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Ferroptosis ; Blood-Brain Barrier/ultrastructure* ; Brain Ischemia/metabolism* ; Cerebral Infarction ; Reperfusion Injury/metabolism* ; Isoflavones/therapeutic use* ; Infarction, Middle Cerebral Artery

Objective To evaluate the effect of surgical reconstruction of extracranial vertebral artery and to summarize the experience. Methods The clinical data of 15 patients undergoing surgical reconstruction of extracranial vertebral artery from September 2018 to June 2022 were collected.The operation methods,operation duration,intraoperative blood loss,operation complications,and relief of symptoms were retrospectively analyzed. Results Eleven patients underwent vertebral artery (V1 segment) to common carotid artery transposition,two patients underwent endarterectomy of V1 segment,two patients underwent V3 segment to external carotid artery bypass or transposition.The operation duration,intraoperative blood loss,and blocking time of common carotid artery varied within 120-340 min,50-300 ml,and 12-25 min,with the medians of 240 min,100 ml,and 16 min,respectively.There was no cardiac accident,cerebral hyperperfusion syndrome,cerebral hemorrhage or lymphatic leakage during the perioperative period.One patient suffered from cerebral infarction and three patients suffered from incomplete Horner's syndrome after the operation.During the follow-up (4-45 months,median of 26 months),there was no anastomotic stenosis,new cerebral infarction or cerebral ischemia. Conclusion Surgical reconstruction of extracranial vertebral artery is safe and effective,and individualized reconstruction strategy should be adopted according to different conditions.
Humans ; Vertebral Artery/surgery* ; Blood Loss, Surgical ; Retrospective Studies ; Brain Ischemia ; Cerebral Infarction

OBJECTIVES: Restoration of blood circulation within "time window" is the principal treating goal for treating acute ischemic stroke. Previous studies revealed that delayed recanalization might cause serious ischemia/reperfusion injury. However, plenty of evidences showed delayed recanalization improved neurological outcomes in acute ischemic stroke. This study aims to explore the role of delayed recanalization on blood-brain barrier (BBB) in the penumbra (surrounding ischemic core) and neurological outcomes after middle cerebral artery occlusion (MCAO). METHODS: Recanalization was performed on the 3rd day after MCAO. BBB disruption was tested by Western blotting, Evans blue dye, and immunofluorescence staining. Infarct volume and neurological outcomes were evaluated on the 7th day after MCAO. The expression of fibroblast growth factor 21 (FGF21), fibroblast growth factor receptor 1 (FGFR1), phosphatidylinositol-3-kinase (PI3K), and serine/threonine kinase (Akt) in the penumbra were observed by immunofluorescence staining and/or Western blotting. RESULTS: The extraversion of Evans blue, IgG, and albumin increased surrounding ischemic core after MCAO, but significantly decreased after recanalization. The expression of Claudin-5, Occludin, and zona occludens 1 (ZO-1) decreased surrounding ischemic core after MCAO, but significantly increased after recanalization. Infarct volume reduced and neurological outcomes improved following recanalization (on the 7th day after MCAO). The expressions of Claudin-5, Occludin, and ZO-1 decreased surrounding ischemic core following MCAO, which were up-regulated corresponding to the increases of FGF21, p-FGFR1, PI3K, and p-Akt after recanalization. Intra-cerebroventricular injection of FGFR1 inhibitor SU5402 down-regulated the expression of PI3K, p-Akt, Occludin, Claudin-5, and ZO-1 in the penumbra, which weakened the beneficial effects of recanalization on neurological outcomes after MCAO. CONCLUSIONS Delayed recanalization on the 3rd day after MCAO increases endogenous FGF21 in the penumbra and activates FGFR1/PI3K/Akt pathway, which attenuates BBB disruption in the penumbra and improves neurobehavior in MCAO rats.
Animals ; Rats ; Blood-Brain Barrier/metabolism* ; Brain Ischemia ; Claudin-5/metabolism* ; Infarction, Middle Cerebral Artery/metabolism* ; Ischemic Stroke/metabolism* ; Occludin/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats, Sprague-Dawley ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Reperfusion Injury/metabolism*

This study aims to observe the therapeutic effect of salidroside on cerebral ischemia-reperfusion(I/R) model rats, and to specifically explore the protection of salidroside on endothelial cell barrier after I/R and the mechanism. In the experiment, SD rats were randomized into sham group, model group, and high-, medium-, and low-dose(10, 5, and 2.5 mg·kg~(-1)) salidroside groups. The suture method was used to induce I/R in rats. The infarct area, neurobehavioral evaluation, and brain water content were used to evaluate the efficacy of salidroside. As for the experiment on the mechanism, high-dose and low-dose salidroside groups were designed. The pathological morphology was observed based on hematoxylin and eosin(HE) staining, and ultrastructure of vascular endothelial cells based on transmission electron microscopy. The content of nitric oxide(NO) in serum, four indexes of blood coagulation, and the content of von Willebrand factor(vWF) in plasma were measured. Western blot(WB) and immunofluorescence(IF) were employed to determine the expression of tight junction proteins(ZO-1, occluding, and claudin-1) and matrix metalloproteinase 9(MMP-9) in the cortex. The results showed that the model group had obvious neurological deficit, obvious infarct in the right brain tissue, and significant increase in water content in brain tissue compared with the sham group. Compared with the model group, high-dose and low-dose salidroside groups showed decrease in neurobehavioral score, and the high-, medium-, and low-dose salidroside groups demonstrated obviously small infarct area and significant decrease in water content in brain tissue. The results of HE staining and transmission electron microscopy showed that rats had necrosis of neurons, damage of original physiological structure of endothelial cells, and disintegration of the tight junction between endothelial cells after I/R compared with the sham group. Compared with the model group, the high-dose and low-dose salidroside groups showed alleviation of neuron injury and intact physiological structure of endothelial cells. The model group had significantly lower serum level of NO, significantly higher plasma levels of vWF and fibrinogen(FIB), and significantly shorter thrombin time(TT) and prothrombin time(PT) than the sham group. Compared with model group, the high-dose and low-dose salidroside groups increased the serum content of NO in serum, decreased the plasma levels of FIB and vWF, and significantly prolonged TT and PT. WB and IF results showed that the model group had significantly lower levels of ZO-1, occluding, and claudin-1 among endothelial cells and significantly higher level of MMP-9 than the sham group. Compared with the model group, high-dose and low-dose salidroside significantly increased the levels of ZO-1, occluding, and claudin-1 in the cortex. The above experimental results show that salidroside has clear therapeutic effect on I/R rats and protects the brain. To be specific, it alleviates the damage of endothelial cells by increasing NO synthesis in endothelial cells, inhibiting coagulation reaction and MMP-9 expression, up-regulating the expression of ZO-1, occludin, and claudin-1, thereby protecting the brain.
Animals ; Rats ; Matrix Metalloproteinase 9/metabolism* ; Endothelial Cells/metabolism* ; Reperfusion Injury/metabolism* ; Blood-Brain Barrier ; Claudin-1/therapeutic use* ; von Willebrand Factor/therapeutic use* ; Rats, Sprague-Dawley ; Brain Ischemia/metabolism* ; Cerebral Infarction ; Reperfusion ; Water/metabolism*

OBJECTIVE: To investigate the age distribution of Mongolian patients with cerebral infarction caused by thrombosis and the correlation and consistency between thromboelastography (TEG) and four parameters of coagulation. METHODS: The age distribution of 298 Mongolian patients with cerebral infarction treated in Affiliated Hospital of Inner Mongolia Minzu University from January 2020 to December 2021 and their TEG, four items of routin coagulation and platelet count were analyzed retrospectively. The correlation and consistency of above-mentioned two detection methods were statistically analyzed. RESULTS: The onset age of 298 Mongolian patients with cerebral infarction was mainly 61-70 years old, accounting for 38.3%, followed by 51-60 years old, accounting for 26.8%. The R time detected by TEG was linearly correlated with PT and APTT（r=0.186，r=0.152）. K value, MA value and α-Angle measured by TEG was linearly correlated with Fib (r=-0.364，r=0.616，r=0.359), K value, MA value and α-Angle measured by TEG was linearly correlated with Plt (r=0.318，r=0.519，r=0.301). The R time detected by TEG was consistent with PT and APTT, and the Kappa values were 0.252 (P<0.001), 0.336 (P<0.001). K, MA, and α-Angle measured by TEG was consistent with Fib, the Kappa values were 0.265 (P<0.001), 0.289 (P<0.001) and 0.290 (P<0.001), respectively; K、MA and α-Angle measured by TEG was consistent with Plt, the Kappa values were 0.276 (P<0.001), 0.285 (P<0.001) and 0.302 (P<0.001), respectively. CONCLUSION The onset age of Mongolian patients with cerebral infarction caused by thrombosis is mainly 61-70 years old, followed by 51-60 years old. The onset age shows a younger trend. There is a significant correlation between TEG and coagulation, but the consistency is weak, therefore, the two methods can not be replaced each other.
Aged ; Blood Coagulation ; Blood Coagulation Tests/methods* ; Cerebral Infarction ; Humans ; Middle Aged ; Retrospective Studies ; Thrombelastography/methods* ; Thrombosis

OBJECTIVE: To investigate the protective effect of astragalus polysaccharide (APS) against blood-brain barrier in a rat model of middle cerebral artery occlusion (MCAO) and the role of P2X7R channel in the protective mechanism. METHODS: In rat microglial cell models of oxygen and glucose deprivation (OGD) or ATP treatment, the formation of blood-brain barrier in vitro was assessed using the leak test, and the effect of APS on the permeability of the blood-brain barrier was determined using LC-MS. In 12 SD rats, MCAO model was established followed by treatment with intraperitoneal injection of normal saline (n= 6) or APS (45 mg/kg, n=6) for 3 consecutive days, with another 6 rats without MCAO receiving saline injections as the control group. The permeability of the blood-brain barrier of the rats was evaluated by determining Evans blue (EB) extravasation, and ATP content in the brain tissue was detected using ELISA; the expression levels of matrix metalloproteinase-9 (MMP-9) and P2X7R in the brain tissue were detected with Western blot. RESULTS: In the in vitro cell model of OGD or ATP treatment, APS treatment obviously promoted the repair of blood-brain barrier integrity. In the rat models, the EB content in the brain tissue and the blood-brain barrier permeability increased significantly in MCAO+saline group and MCAO+APS group as compared with those in the control group (P < 0.01). Compared with saline treatment, APS treatment significantly decreased EB content in the brain tissue and improved the blood-brain barrier permeability in the MCAO rats (P < 0.05). MCAO caused a significant reduction of ATP content and obviously increased the expression levels of MMP-9 and P2X7R in the brain tissue of the rats (P < 0.01), and these changes were significantly alleviated after APS treatment (P < 0.01 or 0.05). CONCLUSION APS can protect the brain tissue of MCAO rats by stabilizing the internal environment, down-regulating the expression of MMP-9 and improving the permeability of blood-brain barrier under cerebral ischemia and hypoxia, and its mechanism may involve the inhibition of P2X7R channel.
Animals ; Rats ; Rats, Sprague-Dawley ; Blood-Brain Barrier ; Infarction, Middle Cerebral Artery ; Matrix Metalloproteinase 9 ; Polysaccharides/pharmacology* ; Evans Blue ; Oxygen ; Glucose ; Adenosine Triphosphate

OBJECTIVE: The key point of anesthesia management in carotid endarterectomy (CEA) is to maintain adequate cerebral perfusion during carotid artery occlusion. Placement of shunt is one of the common surgical methods. This study analyzed the effects of different shunt strategies on cerebral infarction after carotid endarterectomy. METHODS: A total of 443 patients who underwent CEA under general anesthesia within 2 years were divided into imaging group (based on preoperative imaging data as the basis for shunt) and stump pressure group (based on intraoperative stump pressure as the basis for shunt). The preoperative demographic data, past medical history, degree of cervical vascular stenosis, blood pressure at each time point during the perioperative period, vascular blocking time, whether to place the shunt, postoperative hospital stay, cerebral infarction during hospitalization, and other adverse events were collected and compared between the two groups. On this basis, the preoperative and intraoperative conditions with significant differences were matched with propensity scores, and the influence of different shunt strategies on postoperative cerebral infarction was analyzed. RESULTS: In the study, 268 patients in the imaging group and 175 patients in the stump pressure group underwent CEA under general anesthesia. There were statistically significant differences in basic conditions and blood pressure at each time point between the two groups. After matching the propensity scores, 105 patients in each of the two groups were matched. The basic conditions of the patients before surgery and the difference in blood pressure of the two groups at each time point were not statistically significant. There was no significant diffe-rence in the incidence of postoperative cerebral infarction between the two groups (1.9% vs. 1.0%, P>0.999). The intraoperative shunt rate in the imaging group was lower than that in the stump pressure group (0 vs. 22.9%, P < 0.001). The postoperative hospital stay in the imaging group was 8 (7, 8) days, which was longer than the stump pressure group 5 (4, 6) days (P < 0.001). CONCLUSION The rate of the shunt was lower according to preoperative imaging examination than that according to the residual pressure in our hospital. There is no significant difference in the incidence of cerebral infarction during the postoperative hospital stay. The effect of different shunt strategies on cerebral infarction needs further study.
Anesthesia, General ; Blood Pressure ; Cerebral Infarction/prevention & control* ; Endarterectomy, Carotid/adverse effects* ; Humans ; Prostheses and Implants

In the clinical settings, disseminated intravascular coagulation (DIC) and complications such as hemorrhage are commonly seen in acute promyelocytic leukemia patients, whereas thrombosis is rarely reported. We reported a case here that the patient presented with cerebral infarction as the first manifestation. During the admission, the patient encountered differentiation syndrome, pulmonary embolism, pulmonary hemorrhage, and myocardial ischemia, as well as bleeding and thrombosis complications. Hence the patient was diagnosed as DIC. After the treatment of blood transfusion instead of anticoagulation, his condition was stable and the remission was completely achieved. The treatment experience provides guides for other patients with similar complications of simultaneous bleeding and thrombosis.
Blood Coagulation ; Cerebral Infarction ; Disseminated Intravascular Coagulation ; etiology ; Humans ; Leukemia, Promyelocytic, Acute ; complications ; Thrombosis

To study the effect of modified Buyang Huanwu Decoction on the hemorrhagic transformation after intravenous thrombolysis of recombinant tissue type plasminogen activator(rt-PA) in patients with super early(onset time<4. 5 h) cerebral infarction. From March 2016 to July 2018,at the brain disease zone of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,212 cases of super early cerebral infarction were selected and divided into two group according to the randomized complete blocks designs: control group(106 cases) and traditional Chinese medicine group(106 cases). The control group was treated with rt-PA intravenous thrombolysis,while the traditional Chinese medicine group was treated with modified Buyang Huanwu Decoction in addition to the therapy of the control group. Both groups were treated for 14 days. Neurological deficit score,serum matrix metalloproteinase-9(MMP-9),neuron specific enolase(NSE),vascular endothelial growth factor(VEGF) and plasma cellular fibronectin(c-FN) levels,the incidence of hemorrhagic transformation,clinical efficacy and adverse drug reactions before and after treatment were compared between the two groups. According to the findings,at the 14 thday after treatment,the rank sum test of the grade data showed that the clinical efficacy of the traditional Chinese medicine group was better than that of the control group(Z =-2. 033,P = 0. 042); on the basis of χ2 test,the total efficiency of the traditional Chinese medicine group was higher than that of the control group(χ2= 4. 895,P =0. 027); the hemorrhagic transformation rate of the traditional Chinese medicine group was lower than that of the control group within14 days of treatment(χ2= 3. 962,P = 0. 047). MMP-9 levels in the traditional Chinese medicine group were lower than those in the control group at the 3 rd,5 th,7 th,10 th,14 thd after treatment(t =-2. 474,-3. 022,-5. 163,-6. 998,-9. 821; P = 0. 014,0. 003,0,0,0). The improvement of c-FN,NSE,VEGF and NIHSS scores in the traditional Chinese medicine group was superior to that of the control group after 14 days of treatment(t =-2. 343,-3. 187,-2. 129,-3. 105; P = 0. 020,0. 002,0. 034,0. 002). No obvious adverse reactions of modified Buyang Huanwu Decoction were observed during 14 days of treatment. Modified Buyang Huanwu Decoction could reduce the expressions of MMP-9,c-FN,NSE and VEGF after rt-PA intravenous thrombolysis in patients with super early cerebral infarction,and decrease the hemorrhagic transformation rate after thrombolysis,with high safety.
Cerebral Infarction ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Fibronectins ; blood ; Humans ; Matrix Metalloproteinase 9 ; blood ; Medicine, Chinese Traditional ; Phosphopyruvate Hydratase ; blood ; Recombinant Proteins ; therapeutic use ; Thrombolytic Therapy ; Tissue Plasminogen Activator ; therapeutic use ; Vascular Endothelial Growth Factor A ; blood