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There is a pathological process before the attack of stroke. The current primary and secondary preventions of stroke focus on the cerebral vascular conditions, risk factors, and triggering factors. However, the stroke-prone status followed by the occurrence of stroke has not been paid appropriate attention to, which is named in this article as the process of stroke attack. The biomarkers implying the stroke-prone status would inspire innovative ideas to study the process of stroke attack, and help find the precise prevention through the whole process of stroke.
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Objective:To investigate the correlation between asymmetrically prominent cortical veins (APCV) on susceptibility-weighted imaging (SWI) and early neurological deterioration (END) in patients with acute ischemic stroke.Methods:From October 2016 to September 2018, patients with acute ischemic stroke admitted to the Department of Neurology, Donghua Hospital Affiliated to Sun Yat-sen University were enrolled retrospectively. They completed MRI within 3 d of onset. APCV was evaluated using SWI. END was defined as the National Institutes of Health Stroke Scale (NHISS) score at any time point within 7 d after the onset increased by ≥2 or the motor function item score increased by ≥1 from baseline. Multivariate logistic regression analysis was used to determine the independent correlation between APCV and END. Results:A total of 133 patients with acute ischemic stroke were enrolled, including 40 females and 93 males, with a median age of 57.3 years (interquartile range: 47.5-67.5 years). Baseline NIHSS score was 5.9±5.0. Fifty-one (38.3%) patients had APCV, and 38 (28.6%) had END. The proportions of APCV, ipsilateral large vessel stenosis, and patients receiving anticoagulation after admission were significantly different between the END group and the non-END group ( P<0.05). Multivariate logistic regression analysis showed that after adjusting for age and gender, APCV was an independent risk factor for END in patients with acute ischemic stroke (odds ratio 6.907, 95% confidence interval 2.798-17.052; P<0.001). Conclusions:APCV on SWI was an independent risk factor for END in patients with acute ischemic stroke.
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Epidemiological studies and clinical observations have indicated that cold temperature can trigger the occurrence of stroke in individuals at high risk.However,the underlying mechanisms are still unknown.Matrix metalloproteinase-9 (MMP-9) has been found to be associated with the formation,progression and rapture of atherosclerotic plaques and cerebral aneurysms,which is the pathological basis of stroke.Cold temperature activates renin-angiotensin system (RAS) in circulation and tissue.Angiotensin Ⅱ has been implicated in the inducing MMP-9 expression and activation.An increase of MMP-9 may facilitate destabilization and rupture of atherosclerotic plaques or cerebral aneurysms,resulting in the occurrence of stroke.
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Cold wave will increase the incidence of stroke,especially in individuals with vascular disease such as hypertension.The blood pressure fluctuations induced by cold wave may be the main cause of stroke onset.The main responsible mechanisms for blood pressure changes are related to hormone changes,vasomotor factor disorders,calcium channel changes,hemodynamic changes,etc.All of these,the activation of the renin-angiotensin-aldosterone system plays a leading role.Therefore,actively taking warm measures during cold wave can effectively prevent the occurrence of stroke.
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The cold wave is one of the common meteorological factors which related to occurrence of disease,and growth of animals and plants.Due to seasonal restrictions and differences of the main indicators of each cold wave,it is difficult to be consistent when studying the relationship between cold wave and disease,cold wave and growth of animals and plants.In order to make the experimental results more objective and credible,it is necessary to simulate a cold spell artificially.The key technique for simulating a cold wave is to control the temperature manually,so that can achieve the standard of cold wave.Nowadays,the equipments for cold wave simulating include "artificial climate chamber" or "climate simulator",which can be used in the study of the relationship between cold wave and disease,cold wave and growth of animals and plants.The intelligent artificial climate chambers can successfully create an experimental environment that similar to the natural cold wave,thus the study of the relationship between temperature and growth or incidence of animals and plants is no longer restricted by seasonal restrictions,and maintains the consistency between different artificial cold waves,which is beneficial for analysis and judgment.However,the intelligent artificial climate chambers still needs to be further improved in terms of expanding space and manual control of air pressure and humidity.
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Objective To investigate the preventive effect and mechanisms of Naoshuantong capsule in stroke induced by artificial cold wave in hypertensive rats.Methods A total of 130 SD rats were randomly divided into a sham operation group (n =30),a model control group (n =50) and a Naoshuantong treatment group (n=50;intragastric administration of Naoshuantong,0.5 g/kg,2/d for 7 days).Renovascular hypertensive rats model were established by two-kidney,two clip method.At 13th week after operation,rats were exposed to artificial cold wave for 3 days (12 h light of 22 ℃ and 12 h dark of 4 ℃,3 cycles).The brain tissue samples were extracted at the end of the experiment.Differential protein proteomic techniques were used for the identification,functional classification and preliminary analysis of the differentially expressed protein spots,and Western blot was used for the validation of some key proteins.Results There was no occurrence of stroke in the sham operation group,and the incidence of stroke in the model control group (36.00％,18/50) was significantly higher than that in the Naoshuantong treatment group (18.00％,9 / 50;x2 =4.110,P =0.043).With the two-dimensional gel electrophoresis analysis,6 different proteins were identified from 14 protein spots.Among them,the up-regulated superoxide dismutase 2 (SOD2) and the down-regulated B-cell lymphoma 10 (Bcl-10) were found to be at the central location of protein interactions,which has been verified by Western blot.Conclusion Naoshuantong can reduce the occurrence of stroke induced by artificial cold wave in renovascular hypertensive rats.SOD2 up-regulating and Bcl-10 downregulating may be involved in the mechanisms of of Naoshuantong in the prevention of cold wave-induced stroke in hypertensive rats.
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ObjectiveTo verify the reliability of the mouse model of cerebral cortical microinfarct induced by two-photon microscopy and to explore its pathological changes.MethodsSeventeen male C57BL/6J mice were randomly divided into a microinfarct group (n=11) or a sham operation group (n=6).A thinned cranial window of 3 mm diameter was performed over the cerebral cortex with a high-speed micro-drill until the small blood vessels were clearly observed under a dissecting microscope.Then, a permanent single cortical penetrating arteriole occlusion was induced with a gradually enhanced ultrashort laser irradiation through the thinned cranial window with two-photon microscopy.At 7 days after modeling, the cerebral microinfarct volume was measured with HE staining, and the neuron loss, activation of glial cells and deposition of 3-nitrotyrosine were assessed using immunohistochemistry.ResultsThe target vessels of cerebral cortex in 8 (72.7%) mice were occluded and the microinfarcts formed in the microinfarct group, and the average microinfarct volume was 317.23±20.29 μm3.There were remarkable neuron loss and microglia infiltration in the infarcted core, a large number of reactive astrocytes surrounding the infarcted lesion, and massive deposition of 3-nitrotyrosine in the peri-infarct area.No infarcts were observed in the sham operation group.The deposition of 3-nitrotyrosine in the sham operation group was significantly less than that in the microinfarct group (8.00±1.48 vs.98.38±9.10;t=23.962, P<0.001).Conclusions The mouse model of cerebral cortical microinfarct induced by two-photon microscopy is reliable, and its histopathologic changes are consistent with the pathologic features of cerebral microinfarct.
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Epidemiological data,clinical observation and animal experiments have shown that cold wave is closely associated with the onset of stroke.When a population with stroke etiology or risk factors is under pre-stroke state,they will have stroke under the influence of various inducing factors.Cold wave is the external factor that causes the body to enter the pre-stroke state and there are many possible mechanisms.The drug intervention of stroke-prone hypertensive rats at 1 week before the cold wave can reduce the occurrence of stroke during cold wave,suggesting that it is of great significance to conduct preventive intervention to the pre-stroke population before the cold wave coming.
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Objective To investigate the correlation between the measurement methods of carotidcerebral pulse wave velocity (ccPWV) and the traditional method of brachial-ankle pulse wave velocity (baPWV).Methods A total of 136 healthy volunteers were divided into a youth group (20-39 years),a middleaged group (40-59 years),and an elderly group (more than 60 years) according to their ages.While detecting baPWV,transcranial Doppler ultrasound was used to simultaneously monitor the ipsilateral common carotid artery and the terminal segment of internal carotid artery.The time differences of the beating points of their cardiac cycles and the distanceses of the skin surfaces between the 2 probes were measured and ccPWV was calculated.Results The systolic blood pressure,pulse pressure and mean arterial pressure in the elderly group were signifificantly higher than those in the middle-aged group and the young group.The ccPWVs in the youth,middle-aged and elderly groups were 418 ± 52 cm/s,489 ±54 cm/s,and 599 ± 58 cm/s,respectively.The elderly group was significantly faster than the middle-aged group (t =7.308,P ＜0.001),and the middle-aged group was significantly faster than the youth group (t=6.758,P＜0.001).A Pearson correlation analysis showed that ccPWV was significantly positively associated with the age (r=0.847,P＜0.001) and baPWV (r =0.548,P ＜0.001).The multiple linear regression analysis showed that ccPWV was significantly positively associated with the age and diastolic blood pressure (partial correlation coefficients were 0.742 and 0.293respectively,P ＜0.001 and ＜0.010 respectively).Conchlusions ccPWV is a new measurement method for cerebrovascular stiffneas,and it has a good correlation with the traditional measurement method.
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As a therapeutic strategy for ischemic stroke,neuroprotective agents are used to antagonize a series of harmful molecular biological events in cerebral ischemia.This article reviewes the current status of neuroprotective agents in the treatment of acute ischemic stroke,and the challenges from pre-clinical evidences translating into the clinical trials.The vascular endothelial cells,glial cells and neurons should be studied as a whole.
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Objective Evaluation of cerebral blood flow in patients with transient ischemic attack (TIA) using cerebral CT perfusion imaging.Methods CT perfusion scan was performed on a consecutive series of 20 patients with clinical definite TIA.Following their initial CT scan at acute stage of TIA, patients underwent two repeat CT perfusion scanning of region of interest at acute stage and one month after symptom remission.Results Mild to moderate decrease in regional cerebral blood flow (rCBF) and unchanged or mildly decrease in regional cerebral blood volume (rCBV) were observed at acute stage in the majority cases.Normal cerebral perfusion was found in 12 cases and mild to moderate decrease of rCBF in 8 cases one month after TIA.During the one-year follow-up period, all of 12 cases with normal cerebral perfusion did not have recurrence while among 8 cases with mild to moderate decrease of rCBF at initial scan, 6 cases had recurrent TIA or cerebral infarction and 2 cases did not have recurrence.Patients with more severe cerebral perfusion defects usually had a shorter interval time between two attacks.Conclusions Intensive intervention should be performed on patients with severe and long lasting decrease of cerebral perfusion.
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BACKGROUND: Critical closing pressure (CCP) is recently thought to play a key role in cerebral blood flow autoregulation as an effective downstream pressure of cerebral circulation and can objectively reflect the cerebrovascular tone, namely the vascular smooth muscle contraction and diastole, which is subjected to dynamic modulation.OBJECTIVE: To dynamically assess the hypertension-induced damage of the contraction function of cerebral microvascular smooth muscles and its correlation with morphological changes based on CCP evaluation.DESIGN: Randomized controlled experiment.SETTING: Institute of Neural Science of Second Hospital Affiliated to Guangzhou Medical College and Department of Neurology, First Hospital Affiliated to Sun Yet-san University.MATERIALS: The experiment was carried out at the Laboratory of Physiological Science of Sun Yet-san University between July 2002 and August 2003. Totally 160 health male SD rats were randomized into control group and hypertension group with 80 rats in each group. METHODS: Stroke-prone renovas cular hyp ortonsive rats were established in rats of the hypertension group by bilateral renal artery occlusion with two clips. The rats in the control group were not subjected to the occlusion with other treatments identical to those of the hypertension group. At the time points of 2, 4, 6, 8, 10, 12, 14 and 16 weeks after operation, respectively, 10 rats were randomly selected from each of the two groups for determination of arterial pressure and CCP. After the measurements the frontal-parietal lobe was obtained from the anaesthetized rats and cut into slices for quantitative analysis of the morphological changes in cerebral microvessels.different postoperative time points.mean arterial pressure in hypertension group obviously increased from the 6th postoperative week with significant difference from that of the control after operation to a level significantly higher than that of the control group at postoperative 14 and 16 weeks [(63.75±7.43) vs (37.28±3.68) mm Hg and (67.37±15.57) vs (38.39t7.41) mm Hg, respectively, P ＜ 0.05].significance from that of the control group at the 8th postoperative week (Paverage arterial pressure and cerebral arteriole tunica media (r=0.906 93,0.811 36, respectively, P ＜ 0.05). The changes in CCP was more obvious in the early and advanced stages of blood pressure elevation, but not so manifest during obvious blood pressure increment, displaying an inverted S-shaped curve of changes (R2=0.996 2, P ＜ 0.05).CONCLUSION: Contraction of the cerebrovascular smooth muscles is enhanced with the dynamic increment of arterial pressure after the development of hypertension. Vascular tone increase is more manifest during the early and advanced stages of hypertension.
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Objective To explore the value cerebral blood flow in prediction of motor recovery of stroke patients. Methods After evaluating the cerebral blood flow velocities of bilateral middle cerebral arteries with TCD during passive elbow movement, 68 patients with cerebral infarction were treated by rehabilitation therapy. The motor function of upper limbs was evaluated with Fugl Meyer before and after 6,12 weeks of treatment. The patients were divided into groups A and B according to the Fugl Meyer scales score of the paralytic upper limb at 12 weeks and the changes of cerebral blood velocities were compared between the two groups. Results The score of upper limb motor function were not different between group B and A before the treatment, but the score of group B was significantly higher than that of group A ( P
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@#ObjectiveTo explore the effects of the serum of traditional Chinese medicine Nao Yi An on glutamate induced cell death in cultured hippocampal neurons of rat and the underlying mechanisms. MethodsHippocampal neurons were cultured. The excitatory amino acid induced toxicity on cultured neurons was investigated. The viability of injured neurons was determined with the measurement of Lactate dehydrogenase (LDH) activity. Mitogen activated protein kinase (MAPK) were determined by immunoprecipitation /kinase assays /western blot detection.ResultsThe serum of Nao Yi-An raised cell viability. The serum of Nao Yi-An upregulated the expression of extracellular regulated protein kinases(ERK) and downregulated the expression of c-Jun N terminal kinase/stress activited protein kinase(JNK) in cultured neurons. The serum of Nao Yi-An induced upregulation of ERK and its anti death action were prevented with the specific ERKs inhibitor PD98059. Conclusions Activation of ERK signaling together with inhibition of JNK signaling by Chinese medicine Nao Yi-An appears to be an important mechanism for its survival effects on cultured hippocampal neurons.
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Objective To search the relative factors of cerebral damage, rebleeding, delayed cerebral ischaemia(DCI) and hydrocephalus after subarachnoid haemorrhage (SAH) by CT scans and clinical findings in acute phase. Methods To analyse the relationship between cerebral damage after SAH and clinical findings: CT scans resulte, age, sex, blood pressure, hyponatraemia, therapeutic methods. Results Cerebral damage were related to the pattern of distritution of SAH on brain CT and hyponatraemia. The high attack rate of rebleeding and DCI is related to presence of blood in the surface of brain, collection of blood in the ventricle, saccula aneurysms or cerebral arteriovenous malformation (AVM) (P＜0.01). Conclusions To forecast of cerebral damage after SAH by study of CT scans showing and clinical findings have clincal significance. According to these findings, we may take some therapeutics to prevent the cerebral damage after SAH.
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Objective To establish a new practical method to assess the cerebral blood flow autoregulation. Methods We assessed the flow velociey of middle cerebral artery with transcranial Doppler and recorded invasively the blood presure simultaneonsly. Then on the basis of critical closing pressure (CCP), the lower limit of cerebral blood flow autoregulation and the blood flow resistance of arterioles were calculated.The data compared with the results generated by routine method. Results The lower limit of autoregulation working out by CCP was 70.88±24.05 mmHg, which was similar to the result measured by routine method. The lower limit of autoregulation and the arteriole resistance in RHR were significantly higher than those of normal controls, and highly relate to arterial blood pressure significantly, especially pulse pressure. Conclusions The physiology and pathology of cerebral blood flow can be evaluated conveniently and accurately by assessment of the lower limit of autoregulation and arterioles resistance with CCP.
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AIM:To study the effect of hypertensive arteriosclerosis on cerebral blood flow autoregulation (CBFA), and to introduce a new method to measure the lower limit. METHODS:The blood velocities and blood pressure was recorded simultaneously and the curves of CBFA were analyzed and classified into classical and non-classical pattern. The lower limit were determined by clinical closing pressure (CCP) and the curve CBFA. RESULTS:When the blood pressure was decreasing, the classical and non-classical pattern of the cerebral blood flow autoregulation were 25% and 75% respectively in normal SD rats, while they were 40.55% and 54.45% respectively in renovascular hypertensive rats (RHR). However, when the blood pressure was elevating, the classical and non-classical pattern were 76.47% and 23.53% respectively in SD rats, while they were all classical in RHR. Furthermore, in SD and RHR ras, the lower limits measured by CCP were well in accordance with that measured by CBFA. CONCLUSION:Hypertensive arteriosclerosis could influence the limits and the patterns of cerebral blood flow autoregulation. The lower limit of CBFA can be measured and analyzed by CCP.
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AIM: To explore clinical significance of the serum changes of neuron-specific enolase (NSE)and S-100 ? protein (S-100 ?) during acute cerebral infarction. METHODS: 59 acute cerebral infarction patients were classified as total anterior circulation infarcts (TACI), partial anterior circulation infarcts (PACI), lacunar infarcts (LACI) and posterior circulation infarcts (POCI). Their serum NSE and S-100 ? concentrations were determinated by enzyme linked immunosorbent assay (ELISA) during stroke onset 6 d, and compared with 32 controls. RESULTS: The every time point serum NSE concentration of TACI was higher than controls (P
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AIM: To explore the structural changes of brain microvasculature and mechanism in microvascular lesion after focal cerebral ischemia with reperfusion. METHODS: Using the techniques of immunohistochemical staining, in situ hybridization,optical microscopy and transmission electron microscopy, the expression of uPA, uPA mRNA, and changes in miocrovascular structure were examined in ischemic focus and perifocal areas after focal cerebral ischemia 2 hours with various time points of reperfusion in stroke-prone renovascular hypertensive rats (RHRSP). RESULTS: The brain edema and hemorrhage were severe 12 hours to 3 days after reperfusion. Ultrastructural change showed that the damage characterizations of the basement membrane were degradation, defection, and exfoliated of basement membrane, while uPA, which attack the basememt membrane around cerebral capillaries and extra-cellular matrix, and uPA mRNA expression increased significantly in ischemic and perifocal areas 12 hour to 3 day after reperfusion. CONCLUSION: The main pathologic mechanism of brain edema and hemorrhage after cerebral ischemia with reperfusion may result from the basement membrane lesion of brain microvasculature. The increase in the expression of uPA in reperfusion area may be the main cause of the basement membrane lesion .