Jiming Powder is a traditional ancient prescription with good therapeutic effect in the treatment of heart failure, but its mechanism lacks further exploration. In this study, a mouse model of coronary artery ligation was used to evaluate the effect and mechanism of Jiming Powder on myocardial fibrosis in mice with myocardial infarction. The study constructed a mouse model of heart failure after myocardial infarction using the method of left anterior descending coronary artery ligation. The efficacy of Jiming Powder was evaluated from multiple angles, including ultrasound imaging, hematoxylin-eosin(HE) staining, Masson staining, Sirius Red staining, and serum myocardial enzyme spectrum detection. Western blot analysis was performed to detect key proteins involved in ventricular remodeling, including transforming growth factor-β1(TGF-β1), α-smooth muscle actin(α-SMA), wingless-type MMTV integration site family member 3a(Wnt3a), β-catenin, matrix metallopeptidase 2(MMP2), matrix metallopeptidase 3(MMP3), TIMP metallopeptidase inhibitor 1(TIMP1), and TIMP metallopeptidase inhibitor 2(TIMP2). The results showed that compared with the model group, the high and low-dose Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVID;s) and diastole(LVID;d), increased the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improved cardiac function in mice after myocardial infarction, and effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactic dehydrogenase(LDH), thus protecting ischemic myocardium. HE staining showed that Jiming Powder could attenuate myocardial inflammatory cell infiltration after myocardial infarction. Masson and Sirius Red staining demonstrated that Jiming Powder effectively inhibited myocardial fibrosis, reduced the collagen Ⅰ/Ⅲ ratio in myocardial tissues, and improved collagen remodeling after myocardial infarction. Western blot results showed that Jiming Powder reduced the expression of TGF-β1, α-SMA, Wnt3a, and β-catenin, decreased the levels of MMP2, MMP3, and TIMP2, and increased the level of TIMP1, suggesting its role in inhibiting cardiac fibroblast transformation, reducing extracellular matrix metabolism in myocardial cells, and lowering collagen Ⅰ and α-SMA content, thus exerting an anti-myocardial fibrosis effect after myocardial infarction. This study revealed the role of Jiming Powder in improving ventricular remodeling and treating myocardial infarction, laying the foundation for further research on the pharmacological effect of Jiming Powder.
Mice ; Animals ; Transforming Growth Factor beta1/metabolism* ; Matrix Metalloproteinase 2/metabolism* ; beta Catenin/metabolism* ; Matrix Metalloproteinase 3/therapeutic use* ; Powders ; Ventricular Remodeling ; Stroke Volume ; Ventricular Function, Left ; Myocardial Infarction/drug therapy* ; Myocardium/pathology* ; Heart Failure/metabolism* ; Collagen/metabolism* ; Creatine Kinase ; Fibrosis

Objective To quantitatively evaluate the associations of infarct size, regional myocardial function examined by cardiac magnetic resonance feature tracking (CMR-FT) strain analysis with infarct location in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention.Methods Cardiac magnetic resonance images were retrospectively analyzed in 95 consecutive STEMI patients with successful reperfusion. The patients were divided into the anterior wall myocardial infarction (AWMI) and nonanterior wall myocardial infarction (NAWMI) groups. Infarct characteristics were assessed by late gadolinium enhancement. Global and regional strains and associated strain rates in the radial, circumferential and longitudinal directions were assessed by CMR-FT based on standard cine images. The associations of infarct size, regional myocardial function examined by CMR-FT strain analysis with infarct location in STEMI patients were evaluated by the Spearman or Pearsonmethod. Results There were 44 patients in the AWMI group and 51 in the NAWMI group. The extent of left ventricular enhanced mass was significantly larger in patients with AWMI compared with the NAWMI group (24.47±11.89, 21.06±12.08 %LV; t=3.928, P = 0.008). In infarct zone analysis, strains in the radial, circumferential and longitudinal directions were remarkably declined in the AWMI group compared with the NAWMI group (z=-20.873, -20.918, -10.357, all P < 0.001). The volume (end-systolic volume index), total enhanced mass and extent of enhanced mass of the left ventricular were correlated best with infarct zone strain in the AWMI group (all P < 0.001). Conclusion In STEMI patients treated by percutaneous coronary intervention, myocardial damage is more extensive and regional myocardial function in the infarct zone is lower in the AWMI group compared with the NAWMI group.
Humans ; Anterior Wall Myocardial Infarction/therapy* ; ST Elevation Myocardial Infarction/pathology* ; Contrast Media ; Retrospective Studies ; Ventricular Function, Left ; Magnetic Resonance Imaging, Cine/methods* ; Gadolinium ; Magnetic Resonance Imaging ; Myocardial Infarction/diagnostic imaging* ; Magnetic Resonance Spectroscopy ; Percutaneous Coronary Intervention ; Stroke Volume

When ischemia or hemorrhagic stroke occurs, astrocytes are activated by a variety of endogenous regulatory factors to become reactive astrocytes. Subsequently, reactive astrocytes proliferate, differentiate, and migrate around the lesion to form glial scar with the participation of microglia, neuron-glial antigen 2(NG2) glial cells, and extracellular matrix. The role of glial scars at different stages of stroke injury is different. At the middle and late stages of the injury, the secreted chondroitin sulfate proteoglycan and chondroitin sulfate are the main blockers of axon regeneration and nerve function recovery. Targeted regulation of glial scars is an important pathway for neurological rehabilitation after stroke. Chinese medicine has been verified to be effective in stroke rehabilitation in clinical practice, possibly because it has the functions of promoting blood resupply, anti-inflammation, anti-oxidative stress, inhibiting cell proliferation and differentiation, and benign intervention in glial scars. This study reviewed the pathological process and signaling mechanisms of glial scarring after stroke, as well as the intervention of traditional Chinese medicine upon glial scar, aiming to provide theoretical reference and research evidence for developing Chinese medicine against stroke in view of targeting glial scarring.
Astrocytes ; Axons/pathology* ; Cicatrix/pathology* ; Gliosis/pathology* ; Humans ; Medicine, Chinese Traditional ; Nerve Regeneration ; Stroke/drug therapy*

Aged ; Brain Ischemia ; blood ; drug therapy ; pathology ; Female ; Fibrinolytic Agents ; therapeutic use ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Stroke ; blood ; drug therapy ; pathology ; Thrombolytic Therapy ; methods ; Treatment Outcome ; Vitamin D ; analogs & derivatives ; blood

Herbal medicines, mainly of plant source, are invaluable source for the discovery of new therapeutic agents for all sorts of human ailments. The complex pathogenesis of stroke and multifactorial effect of herbal medicine and their active constituents may suggest the promising future of natural medicine for stroke treatment. Anti-oxidant, anti-inflammatory, anti-apoptotic, neuroprotective and vascular protective effect of herbal medicines are believed to be efficacious in stroke treatment. Herbs typically have fewer reported side effects than allopathic medicine, and may be safer to use over longer period of time. Herbal medicines are believed to be more effective for the longstanding health complaints, such as stroke. Several medicinal plants and their active constituents show the promising results in laboratory research. However failure in transformation of laboratory animal research to the clinical trials has created huge challenge for the use of herbal medicine in stroke. Until and unless scientifically comprehensive evidence of the efficacy and safety of herbal medicine in ischemic stroke patients is available, efforts should be made to continue implementing treatment strategies of proven effectiveness. More consideration should be paid to natural compounds that can have extensive therapeutic time windows, perfect pharmacological targets with few side effects. Herbal medicine has excellent prospective for the treatment of ischemic stroke, but a lot of effort should be invested to transform the success of animal research to human use.
Animals ; Brain Ischemia ; drug therapy ; Herbal Medicine ; Humans ; Neurons ; pathology ; Neuroprotection ; Phytotherapy ; Stroke ; drug therapy

OBJECTIVETo study features of brain gray matter injury in cerebral infarction patients and intervention of scalp acupuncture by using voxel-based morphology.

METHODSA total of 16 cerebral infarction patients were recruited in this study, and assigned to the scalp acupuncture group and the control group, 8 in each group. Another 16 healthy volunteers were recruited as a normal group. All patients received scanning of T1 structure. Images were managed using VBM8 Software package. Difference of the gray matter structure was compared among the scalp acupuncture group, the control group, and the healthy volunteers.

RESULTSCompared with healthy volunteers, gray matter injury of cerebral infarction patients mainly occurred in 14 brain regions such as cingulate gyrus, precuneus, cuneus, anterior central gyrus, insular lobe, and so on. They were mainly distributed in affected side. Two weeks after treatment when compared with healthy volunteers, gray matter injury of cerebral infarction patients in the scalp acupuncture group still existed in 8 brain regions such as bilateral lingual gyrus, posterior cingulate gyrus, left cuneus, right precuneus, and so on. New gray matter injury occurred in lingual gyrus and posterior cingulate gyrus. Two weeks after treatment when compared with healthy volunteers, gray matter injury of cerebral infarction patients in the control group existed in 23 brain regions: bilateral anterior cingulum, caudate nucleus, cuneate lobe, insular lobe, inferior frontal gyrus, medial frontal gyrus, precuneus, paracentral lobule, superior temporal gyrus, middle temporal gyrus, lingual gyrus, right postcentral gyrus, posterior cingulate gyrus, precentral gyrus, middle frontal gyrus, and so on. New gray matter injury still existed in 9 cerebral regions such as lingual gyrus, posterior cingulate gyrus, postcentral gyrus, and so on.

CONCLUSIONSBrain gray matter structure is widely injured after cerebral infarction. Brain gray matter volume gradually decreased as time went by. Combined use of scalp acupuncture might inhibit the progression of gray matter injury more effectively.

Acupuncture Therapy ; Brain ; physiopathology ; Brain Injuries ; therapy ; Cerebral Infarction ; therapy ; Gray Matter ; pathology ; Humans ; Magnetic Resonance Imaging ; Scalp ; Stroke ; therapy

During the previous years, with the emerging of nanotechnology, the enormous capabilities of nanoparticles have drawn great attention from researchers in terms of their potentials in various aspects of pharmacology. Cerium oxide nanoparticles (nanoceria), considered as one of the most widely used nanomaterials, due to its tempting catalytic antioxidant properties, show a promising potential in diverse disorders, such as cerebral ischemic stroke (CIS), cancer, neurodegenerative and inflammatory diseases. Overwhelming generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) during cerebral ischemia and reperfusion periods is known to aggravate brain damage via sophisticated cellular and molecular mechanisms, and therefore exploration of the antioxidant capacities of nanoceria becomes a new approach in reducing cerebral ischemic injury. Furthermore, utilizing nanoceria as a drug carrier might display the propensity to overcome limitations or inefficacy of other conceivable neuroprotectants and exhibit synergistic effects. In this review, we emphasize on the principle features of nanoceria and current researches concerning nanoceria as a potential therapeutic agent or carrier in improving the prognosis of CIS.
Antioxidants ; therapeutic use ; Brain Ischemia ; drug therapy ; Cerium ; chemistry ; therapeutic use ; Humans ; Nanoparticles ; chemistry ; therapeutic use ; Neuroprotective Agents ; therapeutic use ; Oxidative Stress ; drug effects ; Reactive Nitrogen Species ; metabolism ; Reactive Oxygen Species ; Stroke ; drug therapy ; pathology

OBJECTIVETo assess brush sign (BS) on susceptibility-weighted imaging (SWI) in prediction of hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) after intravenous thrombolysis(IVT).

METHODSPatients with acute cerebral ischemic stroke, who had major cerebral artery occlusion (internal carotid artery, middle cerebral artery M1 and M2), treated with intravenous recombinant tissue plasminogen activator (rt-PA) from August 2009 to October 2014 in the Second Affiliated Hospital, Zhejiang University School of Medicine, were enrolled in the study. All patients underwent SWI scanning. The asymmetry index (AI) was defined as the difference of intensity between ischemic and normal hemispheres on the SWI phase map; according to AI values patients were divided into 3 groups: BS=0(n=9), BS=1 (n=39) and BS=2 (n=18). The relationships between BS and HT and the clinical outcome among the 3 groups were analyzed.

RESULTSSixty-six patients aged 68 ± 13 years were included in the study, including 44 males (67%) and 22 females (33%), and 44 (67%) with acute ischemic stroke. The mean pre-treatment National Institutes of Health Stroke Scale (NIHSS) score was 13 (6-17), and the onset to needle time was (252 ± 88) min. Twenty-six (39.4%) patients had HT, including 18 cases (27.3%) with HI and 8 cases (12.1%) with PH; BS was observed more frequently in HT group than non-HT group. Binary logistic regression analysis showed that BS was independently associated with HT of patients with acute ischemic stroke following IVT (OR=2.589, 95% CI: 1.080-6.210, P=0.033). In those without reperfusion after IVT, patients with higher BS grade had higher HT rate (P=0.023).

CONCLUSIONBrush sign on SWI can be used for predicting hemorrhagic transformation after intravenous thrombolysis in patients with acute ischemic stroke.

Administration, Intravenous ; Aged ; Aged, 80 and over ; Brain Ischemia ; diagnosis ; drug therapy ; Carotid Artery, Internal ; pathology ; Diagnostic Imaging ; Female ; Humans ; Male ; Middle Aged ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Stroke ; diagnosis ; drug therapy ; Thrombolytic Therapy ; Tissue Plasminogen Activator ; administration & dosage ; therapeutic use ; Treatment Outcome ; United States

OBJECTIVETo evaluate the thrombus length on CT perfusion imaging and to assess its predictive value for recanalization and clinical outcome after intravenous thrombolysis therapy (IVT).

METHODSFifty-six consecutive acute ischemic stroke patients with proximal middle cerebral artery (M1 segment) occlusion underwent CT perfusion imaging examination before IVT between June 2009 and May 2015. The onset-to needle time was (214.3 ± 82.0) min, and the pretreatment NIHSS score of patients was 13 (IQR 8-17). The thrombus length was determined as the distance between the proximal and distal thrombus end delineated on dynamic angiography, which was reconstructed from CT perfusion source images. Recanalization was evaluated according to Arterial Occlusive Lesion (AOL) scale, and functional outcome was based on modified Rankin scale (mRS) 3 months after IVT. Logistic regression model was used to investigate the relationship between thrombus length and recanalization, and the optimal cut-off points were determined by receiver operating characteristic curve (ROC).

RESULTSAmong 56 patients, 42 (75%) achieved recanalization 24 h after IVT with mean thrombus length of (9.0 ± 4.7) mm; and 14 (25%) patients remained occlusion with mean thrombus length of (10.0 ± 5.4) mm. Logistic regression analysis demonstrated that thrombus length was an independent predictor for both recanalization (OR=0.869; 95% CI:0.764-0.987; P=0.031) and unfavorable outcome (OR=1.180;95% CI:1.023-1.362; P=0.023). Thrombus length of 11.3 mm was identified as the optimal cut-off value for recanalization (AUC=0.697, sensitivity 71.4%, specificity 76.2%), while thrombus length of 9.9 mm was the optimal cut-off value for unfavorable functional outcome (AUC=0.689, sensitivity 64.7%, specificity 71.4%).

CONCLUSIONThe thrombus length evaluated on CT perfusion imaging is an effective predictor for recanalization and unfavorable outcome after IVT in acute ischemic stroke patients with middle cerebral artery occlusion.

Angiography ; Humans ; Infarction, Middle Cerebral Artery ; pathology ; Logistic Models ; Perfusion Imaging ; Sensitivity and Specificity ; Stroke ; diagnosis ; drug therapy ; Thrombolytic Therapy ; Thrombosis ; diagnosis ; drug therapy ; Tomography, X-Ray Computed

Stroke classified into ischemic and hemorrhagic subtypes, is among the most devastating diseases for human being. Certain drugs could increase the blood viscosity, thereby increasing the potential risk of ischemia. Anti-platelet and anti-coagulation drugs, as the treatment of first choice, increase the risk of intracranial hemorrhage and death. Here, we are the first to propose the concept of drug-related stroke, and discuss the treatment strategy for patients who are complicated with intracranial hemorrhage or plan to receive neurosurgical operation during either anti-platelet or anti-coagulation medication. We hope to arouse the attention for drug related stroke among the clinicians and offer recommendation for clinical intervention.
Drug-Related Side Effects and Adverse Reactions ; pathology ; Humans ; Intracranial Hemorrhages ; complications ; Stroke ; chemically induced ; prevention & control ; therapy