This study aims to investigate the mechanism of acacetin in protecting rats from cerebral ischemia-reperfusion injury via the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. Wistar rats were randomized into sham, model, low-and high-dose acacetin, and nimodipine groups, with 10 rats in each group. The rat model of middle cerebral artery occlusion(MCAO) was established with the improved suture method in other groups except the sham group. The neurological deficit score and cerebral infarction volume of each group were evaluated 24 h after modeling. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interleukin-1β(IL-1β), IL-6, tumor necrosis factor-α(TNF-α), malondialdehyde(MDA), supe-roxide dismutase(SOD), and glutathione(GSH). Western blot was employed to determine the expression levels of B-cell lymphonoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and TLR4/NLRP3 signaling pathway-related proteins(TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1β, and cleaved IL-1β) in the rat brain tissue. Hematoxylin-eosin(HE) staining was employed to reveal the histopathological changes in the ischemic area. Compared with the sham group, the modeling of MCAO increased the neurological deficit score and cerebral infarction volume, elevated the IL-1β, IL-6, TNF-α, and MDA levels and lowered the SOD and GSH levels in the brain tissue(P<0.05). Compared with the MCAO model group, low-and high-dose acacetin and nimodipine decreased the neurological deficit score and cerebral infarction volume, lowered the IL-1β, IL-6, TNF-α, and MDA levels and elevated the SOD and GSH levels in the brain tissue(P<0.05). Compared with the sham group, the model group showed up-regulated protein levels of Bax, TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1β, and cleaved IL-1β and down-regulated protein level of Bcl-2 in the brain tissue(P<0.05). Compared with the MCAO model group, the acacetin and nimodipine groups showed down-regulated protein levels of Bax, TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1β, and cleaved IL-1β and up-regulated protein level of Bcl-2 in the brain tissue(P<0.05). In conclusion, acacetin regulates the TLR4/NLRP3 signaling pathway to inhibit neuroinflammatory response and oxidative stress, thus exerting the protective effect on cerebral ischemia-reperfusion injury in rats.
Rats ; Animals ; NF-kappa B/metabolism* ; bcl-2-Associated X Protein ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Rats, Sprague-Dawley ; Caspase 1/metabolism* ; Toll-Like Receptor 4/metabolism* ; Nimodipine/pharmacology* ; Interleukin-6 ; Rats, Wistar ; Signal Transduction ; Infarction, Middle Cerebral Artery ; Reperfusion Injury/prevention & control* ; Superoxide Dismutase/metabolism*

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

OBJECTIVE: To investigate whether rapamycin treatment starting at 24 h after cerebral ischemia/reperfusion(I/R) has protective effect on brain injury in rats. METHODS: The rat I/R model was established by middle cerebral artery occlusion according to Longa's method. A total of 104 Sprague Dawley rats were randomly divided into sham group, model group, and rapamycin-treated groups (6 h or 24 h after modeling). Neurological function was assessed with neurological severity score (NSS). Triphenyl tetrazolium chloride (TTC) staining and Fluoro-Jade B (FJB) staining were used to examine the infarct volume and neuronal apoptosis, respectively. The expression of p-S6 protein in mTOR signaling pathway was detected by Western blot analysis. RESULTS: Compared with sham group, NSS of the model group was significantly increased and TTC staining indicated obvious infarct area (all <0.01). Furthermore, significantly increased number of FJB-positive cells and p-S6 expression in the penumbra area were shown in the model group (all <0.01). Compared with the model group, both rapamycin-treated groups demonstrated decreased NSS, infarction volume and FJB positive cells as well as p-S6 expression in the penumbra area (<0.05 or <0.01). There was no significant difference between the groups of rapamycin administrated 6 h and 24 h after modeling (all >0.05). CONCLUSIONS Rapamycin treatment starting at 24 h after I/R exhibits protective effect on brain injury in rats.
Animals ; Brain Ischemia ; drug therapy ; Immunosuppressive Agents ; therapeutic use ; Infarction, Middle Cerebral Artery ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Sirolimus ; therapeutic use ; Treatment Outcome

OBJECTIVETo investigate the protective effect of propofol against focal cerebral ischemia/reperfusion (I/R) injury in rats and its relation with gap junction.

METHODSSeventy adult male SD rats were randomly divided into sham-operated group, I/R group, low-, moderate-, and high-dose propofol groups (25, 50, 100 mg/kg; P25, P50, P100 groups, respectively), I/R+CBX group and P100+CBX group. Thread occlusion was used to induce middle cerebral artery occlusion (MCAO) in the mice for 2 h followed by reperfusion for 24 h. Longa's scores were used to evaluate the neurological behavior of the rats. TTC staining was used to measure the cerebral infarction volume and Western blotting was performed to detect the expressions of Cx43, PKC, Bax, and Bcl-2 in the brain of the rats.

RESULTSCompared with the I/R group, the rats pretreated with moderate and high doses of propofol showed significantly reduced neurological behavior scores and cerebral infarction volume percentage, and the effect was more obvious in high-dose propofol pretreatment group. CBX obviously enhanced the protective effect of propofol against I/R injury. Compared with those in the sham-operated group, the protein expression of Cx43 and the Bax/Bcl-2 ratio were increased and the protein expression of PKC was reduced in I/R group, and these changes were significantly reversed by high-dose propofol pretreatment; the effects of propofol were further enhanced by CBX.

CONCLUSIONThe protective effect of propofol against cerebral I/R injury may involve the inhibition of the gap junction via PKC signaling and by reducing the Bax/Bcl-2 ratio.

Animals ; Brain ; metabolism ; Brain Ischemia ; prevention & control ; Connexin 43 ; metabolism ; Gap Junctions ; Infarction, Middle Cerebral Artery ; Male ; Propofol ; pharmacology ; Protein Kinase C ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Signal Transduction ; bcl-2-Associated X Protein ; metabolism

PURPOSE: In this study, we investigated the stroke mechanism and the factors associated with ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF) who were on optimal oral anticoagulation with warfarin. MATERIALS AND METHODS: This was a multicenter case-control study. The cases were consecutive patients with NVAF who developed cerebral infarction or transient ischemic attack (TIA) while on warfarin therapy with an international normalized ratio (INR) > or =2 between January 2007 and December 2011. The controls were patients with NVAF without ischemic stroke who were on warfarin therapy for more than 1 year with a mean INR > or =2 during the same time period. We also determined etiologic mechanisms of stroke in cases. RESULTS: Among 3569 consecutive patients with cerebral infarction or TIA who had NVAF, 55 (1.5%) patients had INR > or =2 at admission. The most common stroke mechanism was cardioembolism (76.0%). Multivariate analysis demonstrated that smoking and history of previous ischemic stroke were independently associated with cases. High CHADS2 score (> or =3) or CHA2DS2-VASc score (> or =5), in particular, with previous ischemic stroke along with > or =1 point of other components of CHADS2 score or > or =3 points of other components of CHA2DS2-VASc score was a significant predictor for development of ischemic stroke. CONCLUSION: NVAF patients with high CHADS2/CHA2DS2-VASc scores and a previous ischemic stroke or smoking history are at high risk of stroke despite optimal warfarin treatment. Some other measures to reduce the risk of stroke would be necessary in those specific groups of patients.
Aged ; Aged, 80 and over ; Anticoagulants/adverse effects/*therapeutic use ; Atrial Fibrillation/*complications ; Cardiovascular Diseases ; Case-Control Studies ; Cerebral Infarction/complications ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Risk Factors ; Stroke/etiology/*prevention & control ; Warfarin/adverse effects/*therapeutic use

PURPOSE: In this study, we investigated the stroke mechanism and the factors associated with ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF) who were on optimal oral anticoagulation with warfarin. MATERIALS AND METHODS: This was a multicenter case-control study. The cases were consecutive patients with NVAF who developed cerebral infarction or transient ischemic attack (TIA) while on warfarin therapy with an international normalized ratio (INR) > or =2 between January 2007 and December 2011. The controls were patients with NVAF without ischemic stroke who were on warfarin therapy for more than 1 year with a mean INR > or =2 during the same time period. We also determined etiologic mechanisms of stroke in cases. RESULTS: Among 3569 consecutive patients with cerebral infarction or TIA who had NVAF, 55 (1.5%) patients had INR > or =2 at admission. The most common stroke mechanism was cardioembolism (76.0%). Multivariate analysis demonstrated that smoking and history of previous ischemic stroke were independently associated with cases. High CHADS2 score (> or =3) or CHA2DS2-VASc score (> or =5), in particular, with previous ischemic stroke along with > or =1 point of other components of CHADS2 score or > or =3 points of other components of CHA2DS2-VASc score was a significant predictor for development of ischemic stroke. CONCLUSION: NVAF patients with high CHADS2/CHA2DS2-VASc scores and a previous ischemic stroke or smoking history are at high risk of stroke despite optimal warfarin treatment. Some other measures to reduce the risk of stroke would be necessary in those specific groups of patients.
Aged ; Aged, 80 and over ; Anticoagulants/adverse effects/*therapeutic use ; Atrial Fibrillation/*complications ; Cardiovascular Diseases ; Case-Control Studies ; Cerebral Infarction/complications ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Risk Factors ; Stroke/etiology/*prevention & control ; Warfarin/adverse effects/*therapeutic use

OBJECTIVETo discuss the protective effect of Mailuoning injection on ischemia/reperfusion (I/R) injury in rats and its mechanism.

METHODHealthy male adult Sprague-Dawley (SD) rats were randomly divided into the sham operation group, the model group, the edaravone (3 mg x kg(-1)) control group, and Mailuoning high, middle and low-dose groups (4, 2, 1 mL x kg(-1)), with 10 rats in each group, and administered with drugs through tail intravenous injection. The middle cerebral artery occlusion (MCAO) was adopted to establish the rat ischemia/reperfusion model. After the ischemia for 2 h and reperfusion for 24 h, the pathological changes in neurovascular units (NVU) of brain tissues at the ischemia side was observed by HE staining. The expressions of glialfibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Ibal) were detected by the immunohistochemical method. The expressions of tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were detected by the western blotting technique.

RESULTMailuoning injection could significantly improve the pathological changes in cortical penumbra brain tissue UVN of (I/R) rats, reduce the number of GFAP and Ibal positive cells, and significantly decrease the expressions of TNF-alpha, IL-1beta, VCAM-1 and ICAM-1 of brain tissues of I/R rats.

CONCLUSIONMailuoning injection shows an obvious protective effect on UVN of I/R rats. Its mechanism may involve the inhibition of the activation of astrocyte and microglia and the secretion and expression of various inflammatory factors.

Animals ; Brain ; drug effects ; metabolism ; Brain Ischemia ; surgery ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Infarction, Middle Cerebral Artery ; genetics ; metabolism ; Intercellular Adhesion Molecule-1 ; genetics ; metabolism ; Male ; Protective Agents ; administration & dosage ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; genetics ; metabolism ; prevention & control ; Tumor Necrosis Factor-alpha ; genetics ; metabolism ; Vascular Cell Adhesion Molecule-1 ; genetics ; metabolism

OBJECTIVETo tentatively establish a diagnosis and treatment mode for effectively controlling the progress of cerebral microlesions (CM) and preventing the incidence of cerebral infarction (CI) by comparing different intervention modes for treating CM.

METHODSUsing a prospective, nonrandomized, controlled trial, 408 subjects with multiple CM were assigned to the Chinese medical pharmacy intervention group (Group A, 100 case), the aspirin intervention group (Group B, 104 cases), the negative control group (Group C, 100 cases), and the non-intervention group (Group D, 104 cases). No intervention was given to those in Group D. Patients in the other 3 groups were intervened by life style and routine therapies of vasculogenic risk factors. Those in Group A took Guizhi Fuling Pill (GFP) and earthworm powder additionally. Those in Group B took aspirin additionally. They were routinely followed-up. The CM, the changes of vasculogenic risk factors, and the incidence rate of CI were compared among the 4 groups.

RESULTSThe total effective rate of CM was 66.67% in Group A, obviously higher than that of Group B (52.32%), Group C (42.86%), and Group D (37.04%), respectively. It was obviously higher in Group B than in Group D, showing statistical difference (P <0.01, P <0.05). After treatment, the serum levels of LDL-C, TC, and TG were obviously lower in Group A than in Group B (P <0.05); the serum levels of LDL-C and TC were obviously lower in Group A than in Group C (P <0.01); the systolic pressure was obviously lower in Group A than in Group D (P <0.05). The systolic pressure and the serum TC level were obviously lower in Group C than in Group D (P <0.05). The incidence rate of CI was 2.17% (2/92 cases) in Group A, obviously lower than that of Group C (11.36% ,10/88 cases) and Group D (14.44%, 13/90 cases), showing statistical difference (P <0.05). But there was no statistical difference between Group A and Group B (6.74% ,6/89 cases) (P >0.05).

CONCLUSIONSGFP combined earthworm powder could treat CM, control vasculogenic risk factors, and finally prevent the incidence of CI. Standard Chinese medical intervention mode showed the optimal effects in treating CM and preventing the incidence of CI, and perhaps it could be spread clinically.

Adult ; Aged ; Aged, 80 and over ; Aspirin ; therapeutic use ; Brain ; pathology ; Cerebral Infarction ; drug therapy ; pathology ; prevention & control ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy ; Prospective Studies ; Risk Factors ; Treatment Outcome

BACKGROUND AND PURPOSE: Treatment with atorvastatin (80 mg) in stroke secondary prevention for patients with prior intracranial hemorrhage (ICH) has been associated with a higher frequency of ICH. The aim of this study was to determine whether 20 mg/day atorvastatin is linked to stroke recurrence in Chinese ischemic stroke patients with prior ICH. METHODS: A single-center retrospective cohort study was conducted, involving 354 cases from 395 Chinese in-patients who had ischemic stroke with prior ICH history in Beijing Chaoyang hospital from May 1, 2005 to October 31, 2010. Survivors were followed by telephone interviews for 12-60 months. Cox regression and Kaplan-Meier plot analysis were used to evaluate the effect of 20 mg/day atorvastatin on cerebral infarction and ICH recurrence. RESULTS: The overall rate of stroke recurrence was lower in the 20 mg/day atorvastatin group (chi2=6.687, p=0.022) than in the control group. The incidence of cerebral hemorrhage was increased by 20 mg/day atorvastatin for ischemic stroke cases with a history of ICH compared to those not receiving the drug, but the difference was not significant [hazard ratio (HR)=1.097, 95% confidence interval (CI)=0.800-1.243, p=0.980]. The incidence of ischemic stroke recurrence was significantly reduced in subjects receiving atorvastatin (HR=0.723, 95% CI=0.578-0.862, p=0.028), and the mean duration of all stroke recurrences was significantly prolonged, compared with those not exposed to the drug (chi2=5.351, p=0.021). The mean duration of ICH recurrence appeared to have shortened with atorvastatin, but the difference was not significant (chi2=0.680, p=0.480), and the mean duration of cerebral infarction recurrence was significantly prolonged (chi2=8.312, p=0.004). CONCLUSIONS: Medication with 20 mg/day atorvastatin may be beneficial in reducing ischemic stroke recurrence in ischemic stroke patients with a history of ICH and is not associated with an increased risk of ICH recurrence.
Atorvastatin Calcium ; Asian Continental Ancestry Group ; Cerebral Hemorrhage ; Cerebral Infarction ; Cohort Studies ; Heptanoic Acids ; Humans ; Incidence ; Interviews as Topic ; Intracranial Hemorrhages ; Pyrroles ; Recurrence ; Retrospective Studies ; Secondary Prevention ; Stroke ; Survivors

OBJECTIVETo test whether folic acid offers protection of the brain tissue against acute cerebral infarction in rats.

METHODSSprague-Dawley rats were divided into control (n=8), pre-treatment (n=12) and treatment (n=16) groups, all having routine feed for 7 days. The rats in the control and treatment groups were given normal saline daily, and those in the pre-treatment group received folic acid suspension daily. All the rats were then subject to middle cerebral artery occlusion (MCAO) for 24 h followed by reperfusion. On and after the operation day, the rats in the control group were given normal saline and those in the other two groups were given folic acid suspension daily. Neural function deficiency was evaluated on a daily basis after the operation, and on day 6 after the operation, brain biopsy was performed for examination with TTC staining. Monocyte chemokine -1 (MCP-1) in both normal and infarct tissues was measured by ELISA.

RESULTSOn day 6 after the operation, the neural function deficiency scores of the control, pre-treatment and treatment groups were 4.56∓3.63, 2.94∓2.94 and 1.00∓1.00, and the percentages of the infarct area (to the whole brain area) were (44.23∓10.06)%, (20.64∓6.78)% and (14.61∓13.51)%, respectively. The contents of MCP-1 in the infarct area of the brain tissues were 168.58∓107.21 ng/L, 152.91∓64.78 ng/L, and 97.74∓46.19 ng/L in the 3 groups, respectively.

CONCLUSIONFolic acid can protect brain tissue against acute cerebral infarction in rats.

Animals ; Cerebral Infarction ; drug therapy ; Female ; Folic Acid ; therapeutic use ; Infarction, Middle Cerebral Artery ; drug therapy ; Neuroprotective Agents ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Thrombolytic Therapy