(1) No reports concerning the association of platelet Golgi apparatus with acute cerebral infarction or Golgi apparatus participation in platelet CD40L expression have been published. The precise pathway of CD40L transferring to the platelet cell membrane remains unclear.
(2) After acute cerebral infarction, platelet Golgi tubules and vesicles became significantly thickened and enlarged. Alpha granule number in the platelets was significantly reduced. Only a few alpha granules aggregated around Golgi tubules and vesicles after infarction. Golgi apparatus blocking agent Brefeldin A was used, causing a decrease in CD40L expression.
Blood samples were harvested from the antecubital vein of 20 fasting patients with acute cerebral infarction at 1, 7 and 15 days after onset to prepare blood platelet suspension. Fasting antecubital vein blood was collected from an additional 20 normal adults as controls. Under transmission tron microscope, platelet Golgi tubules and vesicles became significantly thickened, enlarged, and irregular after acute cerebral infarction. Alpha granules in platelets significantly reduced in number, especially 1 day after cerebral infarction. Under immunoelectron microscopy, a few alpha granules aggregated around Golgi tubules and vesicles after infarction. These results suggested that platelet Golgi apparatus displayed significant morphological changes, which were possibly associated with enhanced synthetic and secretory functions of activated platelets after acute cerebral infarction. This study used Golgi apparatus blocking agent Brefeldin A to block Golgi apparatus in an aim to study the effects of Golgi apparatus on CD40L expression on the surface of activated platelets. Flow cytometry revealed that CD40L expression on activated platelet surfaces decreased significantly when Golgi apparatus was blocked, which indicated that Golgi apparatus participated in the synthesis and transport of CD40L to the platelet surface.
Prenatal alcohol exposure, especially during early pregnancy, can lead to fetal alcohol syndrome. The pharmacological and toxicological mechanisms of ethanol are related to the effects of ceramide. In this study, we established an alcohol exposure model in wild-type mice and in knockout mice for the key enzyme involved in ceramide metabolism, sphingomyelin synthase 2. This model received daily intragastric administration of 25% ethanol, and pups were used at postnatal days 0, 7, 14, 30 for experiments. Serology and immunofluorescence staining found that ethanol exposure dose-dependently reduced blood sphingomyelin levels in two genotypes of pups, and increased neural cell proliferation and the number of new neurons in the hippocampal dentate gyrus. Western blot analysis showed that the relative expression level of protein kinase C α increased in two notypes of pups after ethanol exposure. Compared with wild-type pups, the expression level of the important activator protein of the ceramide/ceramide-1-phosphate pathway, protein kinase C α, was reduced in the hippocampus of sphingomyelin synthase 2 knockouts. Our findings illustrate that ceramide is involved in alcohol-induced neural proliferation in the hippocampal dentate gyrus of pups after prenatal ethanol exposure, and the mechanism may be associated with increased pression of protein kinase C α activating the ceramide/ceramide-1-phosphate pathway.
(1) The population of northeastern China has a high incidence of ischemic stroke. Previous studies have shown that intracranial large-artery atherosclerosis is one of the main causes of ischemic stroke, and that the mechanisms are related to inflammation and thrombosis of the affected arteries.
(2) This study of 89 patients from northeastern China with acute ischemic stroke caused by intracranial large-artery atherosclerosis evaluated the effects of atorvastatin treatment by measuring changes in the levels of markers of inflammation, thrombogenesis, and hyperlipidemia.
(3) Atorvastatin treatment decreased the levels of markers of inflammation, thrombogenesis, and hyperlipidemia.
(4) Most previous studies of patients with acute ischemic stroke caused by large-artery atherosclerosis focused mainly on measurement of the level of a single marker such as C-reactive protein, fibrinogen, or D-dimer. This study measured all three of these values to evaluate the effects of vastatin treatment, and expanded the range of atorvastatin available for the treatment of acute ischemic stroke.
Atorvastatin decreases inflammation and thrombogenesis in patients with carotid artery plaque. Atorvastatin is administered to lower lipid levels, but its anti-inflammatory and anti-thrombogenic effects remain unclear. Eighty-nine patients from northeastern China with acute ischemic stroke caused by large-artery atherosclerosis were randomly divided into the study and control groups. All patients received routine treatment, including antiplatelet therapy, circulatory support, and symptomatic treatment. The study group (n = 43) also received daily atorvastatin 20 mg/d, and the control group (n = 46) received daily placebo pills containing glucose. After 4 weeks, the levels of C-reactive protein, fibrinogen, and D-dimer were significantly lower in the study group than in the control group. Decreases in the levels of C-reactive protein, fibrinogen, and D-dimer were not associated with decreases in the levels of triacylglycerol and low-density lipoprotein cholesterol. These results suggest that atorvastatin reduces inflammation and thrombogenesis independent of its lipid-lowering effects in patients with acute ischemic stroke caused by large-artery atherosclerosis.
(1) Tri-linear interpolation algorithm for fiber tracking can reduce the noise and partial volume effects, thus obtaining more rapid calculations, more tracked fibers, longer and smoother tracked fibers, more obvious orientation and clearer details.
(2) Comparisons of the tri-linear interpolation algorithm and the tensorline algorithm help to define the theoretic application value. Furthermore, the adaptivity and availability of the tri-linear interpolation algorithm in tracking white matter in human brains have been verified through experimental testing, clinical applicability and comparisons with actual anatomical structures.
Diffusion tensor imaging is a unique method to visualize white matter fibers three-dimensionally, non-invasively and in vivo, and therefore it is an important tool for observing and researching neural regeneration. Different diffusion tensor imaging-based fiber tracking methods have been already investigated, but making the computing faster, fiber tracking longer and smoother and the details shown clearer are needed to be improved for clinical applications. This study proposed a new fiber tracking strategy based on tri-linear interpolation. We selected a patient with acute infarction of the right basal ganglia and designed experiments based on either the tri-linear interpolation algorithm or tensorline algorithm. Fiber tracking in the same regions of interest (genu of the corpus callosum) was performed separately. The validity of the tri-linear interpolation algorithm was verified by quantitative analysis, and its feasibility in clinical diagnosis was confirmed by the contrast between tracking results and the disease condition of the patient as well as the actual brain anatomy. Statistical results showed that the maximum length and average length of the white matter fibers tracked by the tri-linear interpolation algorithm were significantly longer. The tracking images of the fibers indicated that this method can obtain smoother tracked fibers, more obvious orientation and clearer details. Tracking fiber abnormalities are in good agreement with the actual condition of patients, and tracking displayed fibers that passed though the corpus callosum, which was consistent with the anatomical structures of the brain. Therefore, the tri-linear interpolation algorithm can achieve a clear, anatomically correct and reliable tracking result.
Autophagy is involved in neural cell death after cerebral ischemia. Our previous studies showed that rapamycin-induced autophagy decreased the rate of apoptosis, but the rate of apoptosis was creased after the autophagy inhibitor, 3-methyladenine, was used. In this study, a suture-occluded method was performed to generate a rat model of brain ischemia. Under a transmission electron microscope, autophagic bodies and autophagy lysosomes were markedly accumulated in neurons at 4 hours post brain ischemic injury, with their numbers gradually reducing over time. Western blotting demonstrated that protein levels of light chain 3-II and cathepsin B were significantly increased within 4 hours of ischemic injury, but these levels were not persistently upregulated over time. Confocal microscopy showed that autophagy was mainly found in neurons with positive light chain 3 signal. Injection of rapamycin via tail vein promoted the occurrence of autophagy in rat brain tissue after cerebral ischemia and elevated light chain 3 and cathepsin B expression. However, injection of 3-methyladenine significantly diminished light chain 3-II and cathepsin B expression. Results verified that autophagic and lysosomal activity is increased in ischemic neurons. Abnormal components in cells can be eliminated through upregulating cell autophagy or inhibiting autophagy after ischemic brain injury, resulting in a dynamic balance of substances in cells. Moreover, drugs that interfere with autophagy may be potential therapies for the treatment of brain injury.
(1) In this study, we aimed to determine whether cytoglobin could scavenge oxygen free radicals produced by hypoxia-induced oxidative stress and protect cells.
(2) Cytoglobin and hypoxia-inducible factor-1α expression was strongly upregulated by hypoxia. Overexpression of cytoglobin is a protective mechanism against hypoxia in SH-SY5Y cells. In comparison, the expression of hypoxia-inducible factor-1α was nearly undetectable in normal SH-SY5Y cells.
A plasmid for cytoglobin expression, pAcGFP1-C1-cytoglobin, was transfected into SH-SY5Y cells. Cobalt chloride was used to establish a model of hypoxia. Western blotting indicated that cytoglobin was overexpressed and there was low expression of hypoxia-inducible factor-1α in SH-SY5Y cells after transfection. Following cobalt chloride-induced hypoxia, cytoglobin and hypoxia-inducible factor-1α expression gradually increased in SH-SY5Y cells. Flow cytometry showed that with increasing duration of hypoxia, the proportion of normal cells significantly diminished in the transfected and non-transfected groups. The proportion of cells in the early stages of apoptosis increased. However, the proportion of apoptotic cells was significantly lower in the transfected group compared with the non-transfected group. These results demonstrate that cytoglobin and hypoxia-inducible factor-1α are strongly up-regulated by hypoxia, and that there is a strong relationship between hypoxia-inducible factor-1α and cytoglobin during hypoxic injury.
This study aimed to summarize therapy experience of carotid endarterectomy, carotid endarterectomy combined with Fogarty catheter embolectomy, and hybrid surgery for the treatment of extracranial internal carotid artery occlusion. The study included 65 patients with extracranial internal carotid artery occlusion who underwent carotid endarterectomy, carotid endarterectomy combined with Fogarty catheter embolectomy, or hybrid surgery in the Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, China between January 2006 and December 2012. Prior to surgery, all patients underwent perfusion CT or xenon CT to evaluate the occlusion. The procedure for each patient was chosen according to digital subtraction angiography data. The carotid artery was successfully recanalized in 46 of 51 patients who underwent carotid endarterectomy, 9 of 10 patients who underwent carotid endarterectomy combined with Fogarty catheter embolectomy, and 3 of 4 patients who underwent hybrid surgery. In patients with symptomatic carotid artery occlusion, the carotid artery can be recanalized by choosing a treatment procedure based on imaging examination findings.
(1) The present study is the first to analyze the difference of Noggin and basic fibroblast growth factor to induce neural precursor differentiation of human embryonic stem cells.
(2) Using a monolayer differentiation method, the differentiation effects of Noggin and basic fibroblast growth factor were compared. Noggin was more effective than basic fibroblast growth factor in the differentiation of neural precursor cells.
The difference between Noggin and basic fibroblast growth factor for the neural precursor differentiation from human embryonic stem cells has not been studied. In this study, 100 μg/L Noggin or 20 μg/L basic fibroblast growth factor in serum-free neural induction medium was used to differentiate human embryonic stem cells H14 into neural precursors using monolayer differentiation. Two weeks after induction, significantly higher numbers of neural rosettes formed in the Noggin-induced group than the basic fibroblast growth factor-induced group, as detected by phase contrast microscope. Immunofluorescence staining revealed expression levels of Nestin, β-III Tubulin and Sox-1 were higher in the induced cells and reverse-transcription PCR showed induced cells expressed Nestin, Sox-1 and Neurofilament mRNA. Protein and mRNA expression in the Noggin-induced group was increased compared with the basic fibroblast growth factor-induced group. Noggin has a greater effect than basic fibroblast growth factor on the induction of human embryonic stem cell differentiation into neural precursors by monolayer differentiation, as Noggin accelerates and increases the differentiation of neural precursors.
(1) In the current study, a rat model of permanent focal cerebral ischemia was used for the first time to demonstrate that 60-minute sevoflurane preconditioning has neuroprotective effects in rats with permanent cerebral ischemia.
(2) Long time (120 minutes) sevoflurane preconditioning had no obvious neuroprotective effects in rats with permanent cerebral ischemia.
(3) Sixty-minute sevoflurane preconditioning exerts the best neuroprotective effects in rats with permanent cerebral ischemia by inhibiting apoptosis.
Sevoflurane preconditioning has neuroprotective effects in the cerebral ischemia/reperfusion model. However, its influence on permanent cerebral ischemia remains unclear. In the present study, the rats were exposed to sevoflurane for 15, 30, 60, and 120 minutes, followed by induction of permanent cerebral ischemia. Results demonstrated that 30- and 60-minute sevoflurane preconditioning significantly reduced the infarct volume at 24 hours after cerebral ischemia, and 60-minute lurane preconditioning additionally reduced the number of TUNEL- and caspase-3-positive cells in the ischemic penumbra. However, 120-minute sevoflurane preconditioning did not show evident neuroprotective effects. Moreover, 60-minute sevoflurane preconditioning significantly attenuated neurological deficits and infarct volume in rats at 4 days after cerebral ischemia. These findings indicated that 60-minute sevoflurane preconditioning can induce the best neuroprotective effects in rats with permanent cerebral ischemia through the inhibition of apoptosis.
(1) Endogenous and exogenous nerve cells have a limited capacity of differentiation and growth, so some methods are needed to stimulate cell proliferation, promote cell survival and trigger neurite outgrowth.
(2) This study used four collagen treatments to culture primary nerve cells to find an optimal matrix to induce neurite outgrowth and cell survival.
(3) Results from this study confirmed that hydrolyzed collagen facilitated cell survival and neurite outgrowth.
In this study, we investigated the effects of hydrolyzed and non-hydrolyzed collagen and two-dimensional and three-dimensional collagen matrices on cell survival, attachment and neurite outgrowth of primary cultured nerve cells using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay and inverted microscopy. Hydrolyzed collagen facilitated nerve cell survival and neurite outgrowth, but it had no obvious influences on cell attachment. In contrast, non-hydrolyzed two-dimensional collagen matrix had no obvious effects on neurite outgrowth. These findings suggest that hydrolyzed collagen is an ideal nerve cell culture media.
(1) Increased brain cell apoptosis in intrauterine growth-restricted fetal rats is a key reason for unfavorable long-term prognosis of the nervous system.
(2) Taurine supplement in pregnant rats noticeably reduced cell apoptosis, promoted glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in brain tissue of intrauterine growth-restricted fetal rats.
(3) Experimental results provided theoretical evidence for preventing or lessening brain injury and promoting brain development in intrauterine growth-restricted fetuses using a suitable measurement before parturition.
From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.