BACKGROUND: Endothelial dysfunction, the initial pathogenic factor in atherosclerosis, can be alleviated via transient limb ischemia. We observed the effects of regular transient limb ischemia (RTLI) on atherosclerosis in hypercholesterolemic rabbits. METHODS: Twenty-eight rabbits were randomized to control, cholesterol, sham, ischemia groups (n = 7 each) between October 2010 and March 2011. They were fed a normal diet in the control group and hypercholesterolemic diet in other groups for 12 weeks. Six cycles of RTLI were performed once per day on the ischemia group. Serum samples were prepared to measure the total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) before the experiment (W0), at the end of weeks 4, 8, 12 (W4, W8, W12). The whole aorta was harvested at W12 and stained using Sudan IV to identify the plaque. The plaque area was measured using Image J. Results were analyzed by analysis of variance or rank sum test. RESULTS: Concentrations of TC in the cholesterol group were higher than those in the control group at W4 (29.60 [23.75, 39.30] vs. 1.00 [0.80, 1.55], Z = -2.745, P = 0.006), W8 (41.78 [28.08, 47.37] vs. 0.35 [0.10, 0.68], Z = -2.739, P = 0.006), W12 (48.32 [40.04, 48.95] vs. 0.61 [0.50, 0.86], Z = -2.739, P = 0.006). Similar results were obtained for HDL-C and LDL-C. Serum concentrations of TC, HDL-C, and LDL-C in the hypercholesterolemic groups had no differences (all P > 0.05). The percentage of plaque area in the cholesterol group was higher than that in the control group (47.22 ± 23.89% vs. 0, Z = -2.986, P = 0.003). Square root of the percentage of plaque area was smaller in the ischemia group than that in the cholesterol (0.44 ± 0.13 vs. 0.67 ± 0.18, P = 0.014) or sham groups (0.44 ± 0.13 vs. 0.61 ± 0.12, P = 0.049). CONCLUSION In hypercholesterolemic rabbits, RTLI might prevent atherosclerosis progression by reducing the percentage of plaque area.
Animals ; Atherosclerosis ; blood ; prevention & control ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Extremities ; pathology ; Hypercholesterolemia ; blood ; Ischemic Attack, Transient ; blood ; Ischemic Postconditioning ; methods ; Male ; Rabbits ; Triglycerides ; blood

Artemisia capillaris Thunberg is a medicinal plant used as a traditional medicine in many cultures. It is an effective remedy for liver problems including hepatitis. Recent pharmacological reports have indicated that Artemisia species can exert various neurological effects. Previously, we reported a memory-enhancing effect of Artemisia species. However, the mechanisms underlying the neuroprotective effect of A. capillaris (AC) are still unknown. In the present study, we investigated the effect of an ethanol extract of AC on ischemic brain injury in a mouse model of transient forebrain ischemia. The mice were treated with AC for seven days, beginning one day before induction of transient forebrain ischemia. Behavioral deficits were investigated using the Y-maze. Nissl and Fluoro-jade B staining were used to indicate the site of injury. To determine the underlying mechanisms for the drug, we measured acetylcholinesterase activity. AC (200 mg·kg) treatment reduced transient forebrain ischemia-induced neuronal cell death in the hippocampal CA1 region. The AC-treated group also showed significant amelioration in the spontaneous alternation of the Y-maze test performance, compared to that in the untreated transient forebrain ischemia group. Moreover, AC treatment showed a concentration-dependent inhibitory effect on acetylcholinesterase activity in vitro. Finally, the effect of AC on forebrain ischemia was blocked by mecamylamine, a nonselective nicotinic acetylcholine receptor antagonist. Our results suggested that in a model of forebrain ischemia, AC protected against neuronal death through the activation of nicotinic acetylcholine receptors.
Acetylcholinesterase ; metabolism ; Animals ; Artemisia ; Cell Death ; drug effects ; Cholinergic Antagonists ; pharmacology ; Disease Models, Animal ; Ethanol ; chemistry ; Hippocampus ; pathology ; physiopathology ; Ischemic Attack, Transient ; drug therapy ; pathology ; physiopathology ; Male ; Mecamylamine ; pharmacology ; Memory ; drug effects ; Mice ; Mice, Inbred C57BL ; Models, Neurological ; Neuroprotective Agents ; administration & dosage ; pharmacology ; Phytotherapy ; Plant Components, Aerial ; chemistry ; Plant Extracts ; administration & dosage ; pharmacology ; Receptors, Cholinergic ; metabolism

OBJECTIVE: The purpose of this study was to correlate permeability parameters measured with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using a clinical 3-tesla scanner with extravasation of Evans blue in a rat model with transient cerebral ischemia. MATERIALS AND METHODS: Sprague-Dawley rats (n = 13) with transient middle cerebral artery occlusion were imaged using a 3-tesla MRI with an 8-channel wrist coil. DCE-MRI was performed 12 hours, 18 hours, and 36 hours after reperfusion. Permeability parameters (K(trans), v(e), and v(p)) from DCE-MRI were calculated. Evans blue was injected after DCE-MRI and extravasation of Evans blue was correlated as a reference with the integrity of the blood-brain barrier. Correlation analysis was performed between permeability parameters and the extravasation of Evans blue. RESULTS: All permeability parameters (K(trans), v(e), and v(p)) showed a linear correlation with extravasation of Evans blue. Among them, K(trans) showed highest values of both the correlation coefficient and the coefficient of determination (0.687 and 0.473 respectively, p < 0.001). CONCLUSION: Permeability parameters obtained by DCE-MRI at 3-T are well-correlated with Evans blue extravasation, and K(trans) shows the strongest correlation among the tested parameters.
Animals ; Blood-Brain Barrier/pathology ; Capillary Permeability ; Contrast Media ; Disease Models, Animal ; Evans Blue/analysis ; Ischemic Attack, Transient/*diagnosis ; Magnetic Resonance Imaging/instrumentation/*methods ; Male ; Rats ; Rats, Sprague-Dawley ; Stroke/diagnosis

OBJECTIVE: To explore the expression profile of Ephrin-B2 in the ischemic penumbra after transient focal cerebral ischemia in rats, and to clarify the mechanism of Ephrin-B2 triggering angiogenesis. METHODS: Sprague-Dawley rats were randomly divided into a normal group, a sham operation group and ischemic-reperfusion 1, 3, 7, 14, and 28 d groups. Suture-occluded method was used to establish the focal middle cerebral artery occlusion model and the ischemic brain was reperfused 2 h after the occlusion. Western blot and quantitative real-time reverse-transcription polymerase chain reaction were used to detect the dynamic expression profile of Ephrin-B2 in the penumbra cortex. Double immunofluorescence was used to speculate the location and the co-expression of Ephrin-B2 in blood vessels, neurons and astrocytes. Microvessel density was quantified by the number of CD31+ cells. Rats were subjected to neurologic functional tests by modified neurological severity scores (mNSS) before sacrifice. RESULTS: Compared with the sham group, Ephrin-B2 protein and mRNA level of the penumbra cortex in the ischemic group increased 3 days (P<0.05) after the reperfusion, peaked at day 7 and 14 (P<0.01), and declined at day 28. Double immunofluorescence indicated that Ehprin-b2 was expressed in the neurons, blood vessels and astrocytes; mNSS peaked at day 7, and gradually declined at day 14. The microvessel density of penumbra cortex in the ischemic group increased 3 days (P<0.05) after the reperfusion, peaked at day 14 (P<0.01), and gradually declined at 48 h. CONCLUSION Cerebral ischemia reperfusion induces the over-expression of Ephrin-B2, with a dynamic trend, suggesting that Ehprin-b2 may improve post-stroke functional recovery by enhancing angiogenesis and neurogenesis.
Animals ; Astrocytes ; metabolism ; Brain ; pathology ; Brain Ischemia ; metabolism ; Cerebral Cortex ; metabolism ; Ephrin-B2 ; metabolism ; Infarction, Middle Cerebral Artery ; Ischemic Attack, Transient ; Neurons ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism

OBJECTIVEThis review aims to illustrate the relationship between clinical features and the prognosis of patients with limb-shaking transient ischemic attack (LS-TIA).

DATA SOURCESRelevant articles published in two main Chinese medical periodical databases (China National Knowledge Infrastructure and China Science Periodical Database) from 1986 to June 2013 were identified with keywords "limb shaking" and "transient ischemic attack".

STUDY SELECTIONOriginal articles and case reports about LS-TIA were selected.

RESULTSA total of 63 cases collected from 19 articles were included in the pooled analysis. LS-TIA presented in two cerebrovascular diseases, of which atherosclerotic high-grade stenosis or occlusion in carotid artery system and moyamoya disease formed 95.2% and 4.8%, respectively. Of 63 patients, 11 (17.5%) were once misdiagnosed as epileptic and prescribed useless antiepilepsy drugs. The multivariable Logistic regression model showed a significant protective effect of patients with revascularization therapy on prognosis, compared with patients treated with drugs (odds ratio 0.20, 95% CI 0.05-0.74, P = 0.016).

CONCLUSIONSChronic carotid artery system hypoperfusion can induce limb(s) shaking, followed by high possibility of ischemic stroke in the same brain territorial. Revascularization of the responsible artery may work better than conservative drug-based therapy.

Aged ; Extremities ; physiopathology ; Female ; Humans ; Ischemic Attack, Transient ; pathology ; physiopathology ; Male ; Middle Aged ; Prognosis

OBJECTIVE: We wanted to differentiate between transient ischemic attack (TIA) and minor stroke using fractional anisotropy and three-dimensional (3D) fiber tractography. MATERIALS AND METHODS: The clinical data, conventional magnetic resonance imaging (MRI), diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) were obtained for 45 TIA patients and 33 minor stroke patients. The fractional anisotrophy ratio (rFA) between the lesion and the mirrored corresponding contralateral normal tissue was calculated and analyzed. The spatial relationship between the lesion and the corticospinal tract (CST) was analyzed and the lesion sizes in the minor stroke patients and TIA patients were compared. RESULTS: Twenty-two of the 45 TIA patients (49%) revealed focal abnormalities following DWI. The rFA was significantly lower (p < 0.05) in the stroke patients (0.71 +/- 0.29) compared to that of the TIA patients (1.05 +/- 0.37). The CST was involved in almost all stroke lesions, but it was not involved in 68% of the TIA lesions. The TIA patients had significantly lower CST injury scores (3.25 +/- 1.75) than did the stroke patients (8.80 +/- 2.39) (p = 0.004). CONCLUSION: Our data indicate that TIA and minor stroke can be identified by analyzing the rFA and the degree of CST involvement, and this may also allow more accurate prediction of a patient's long-term recovery or disability.
Aged ; Anisotropy ; Area Under Curve ; Chi-Square Distribution ; Diagnosis, Differential ; Diffusion Tensor Imaging/*methods ; Female ; Humans ; Image Interpretation, Computer-Assisted ; *Imaging, Three-Dimensional ; Ischemic Attack, Transient/*pathology ; Male ; Middle Aged ; ROC Curve ; Sensitivity and Specificity ; Stroke/*pathology

Blood cells are transported into the brain and are thought to participate in neurodegenerative processes following hypoxic ischemic injury. We examined the possibility that transient forebrain ischemia (TFI) causes the blood-brain barrier (BBB) to become permeable to blood cells, possibly via dysfunction and degeneration of endothelial cells in rats. Extravasation of Evans blue and immunoglobulin G (IgG) was observed in the hippocampal CA1-2 areas within 8 h after TFI, and peaked at 48 h. This extravasation was accompanied by loss of tight junction proteins, occludin, and zonula occludens-1, and degeneration of endothelial cells in the CA1-2 areas. Iron overload and mitochondrial free radical production were evident in the microvessel endothelium of the hippocampus before endothelial cell damage occurred. Administration of deferoxamine (DFO), an iron chelator, or Neu2000, an antioxidant, blocked free radical production and endothelial cell degeneration. Our findings suggest that iron overload and iron-mediated free radical production cause loss of tight junction proteins and degeneration of endothelial cells, opening of the BBB after TFI.
Animals ; Blood-Brain Barrier/*metabolism ; Capillary Permeability ; Endothelial Cells/*metabolism ; Evans Blue/metabolism ; Free Radicals/metabolism ; Hippocampus/*metabolism/pathology ; Iron/*metabolism ; Ischemic Attack, Transient/pathology/*physiopathology ; Male ; Membrane Proteins/metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of dauricine on the apoptosis of neuronal cells and the expression of apoptosis-related proteins in the brain penumbra of rats induced by transient focal cerebral ischemia-reperfusion injury.

METHODMale SD rats were randomly divided into five groups: sham group (Sham), model group (Model), and Dauricine groups of low, middle and high doses. To make the transient focal cerebral ischemia-reperfusion injury model, the middle cerebral artery on the right side of rat was occluded by inserting a nylon suture through the internal carotid artery for 1 h, followed by reperfusion for 24 h after withdrawing the suture. Dauricine groups, different doses of Dauricine (2.5, 5, 10 mg x kg(-1) as low, middle and high dose respectively) were administered intraperitoneally at the beginning of the cerebral ischemia, and at 11 h and 23 h after reperfusion. At the same time, Sham group and Model group was administered saline as controls. Brain samples of rats were treated with paraformaldehyde perfusion fixation 24 h after blood reperfusion and then collected for making pathological sections. Apoptotic changes of neuronal cells in the brain penumbra of rat were evaluated in situ by terminal deoxyribonucleotidyl transferasemediated dUTP-digoxigenin nick end-labelling (TUNEL). Cytochrome C (Cyt-C) release and the expression of caspase -3 and caspase -9 proteins of the ischemic-reperfusion brain tissue were determined by immunohistochemistry assay.

RESULTTUNEL-positive cells in groups of middle and high doses of dauricine (18.9 +/- 2.02 and 15.9 +/- 2.9 cells/mm2 respectively) decreased significantly compared with model group (25.5 +/- 3.3 cells/mm2, P<0.05). Cyt-C release and the expression of caspase-3 and caspase-9 proteins in groups of middle and high doses of dauricine were also inhibited compared with Model group (P<0.01).

CONCLUSIONThe mechanism of the neuroprotective effect of dauricine after cerebral ischemia-reperfusion injury may parly, related with an inhibition of neuronal cells apoptosis in the penumbra.

Animals ; Apoptosis ; drug effects ; Benzylisoquinolines ; pharmacology ; Caspases ; metabolism ; Cytochromes c ; metabolism ; Dose-Response Relationship, Drug ; Gene Expression Regulation ; drug effects ; Ischemic Attack, Transient ; surgery ; Male ; Neuroprotective Agents ; pharmacology ; Rats ; Reperfusion Injury ; metabolism ; pathology ; prevention & control ; Tetrahydroisoquinolines ; pharmacology

OBJECTIVETo investigate the characteristics of cerebral artery lesions in patients with limb-shaking transient ischemic attacks (LS-TIA) and its treatment.

METHODSWe retrospectively analyzed the clinical data of 20 patients with LS-TIA who received treatment in Peking Union Medical College Hospital from 2005 to 2008.

RESULTSCritical stenosis or occlusion of contralateral arteries were found in the siphonic part of internal carotid artery (ICA) in 6 patients, terminal ICA or proximal middle cerebral artery (MCA) in 6 patients, and distal MCA in 1 patient. Seven patients had proximal ICA occlusion. The brain MRI showed typical watershed cerebral infarctions in 8 patients. EEG studies failed to show epileptiform activity associated with LS-TIA, but found focal frontotemporal lobe slow activity in 6 patients, which was consistent with hypoperfusion area in CT perfusion. Six patients received surgical revascularization and no one recurred.

CONCLUSIONIntracranial artery including the siphonic part of ICA, terminal ICA and proximal MCA stenosis is the main underlying cause of LS-TIA in Chinese, and surgical revascularization may be effective in abolishing the attacks.

Adult ; Aged ; Aged, 80 and over ; Cerebral Arteries ; pathology ; Female ; Humans ; Ischemic Attack, Transient ; complications ; pathology ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Tremor ; etiology

OBJECTIVETo study the changes of insulin-like growth factor-I (IGF-I) in focal cerebral ischemical reperfusion injury model.

METHODSFocal cerebral ischemia was induced in rats using filament method, and the expressions of IGF-I was detected with immunohistochemical staining.

RESULTSThe expression of IGF-I was very low in normal brain tissues, but increased in the infracted area and penumbra after cerebral ischemia. The expressions of IGF-I reached the peak level of 14.83-/+0.48 at days 3 after reperfusion.

CONCLUSIONFocal cerebral ischemia reperfusion injury enhances the expression of endogenous IGF-I.

Animals ; Female ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; metabolism ; pathology ; Insulin-Like Growth Factor I ; biosynthesis ; Ischemic Attack, Transient ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism