Evolution Path of Precursor-Induced High-Temperature Lithiation Reaction during the Synthesis of Lithium-Rich Cathode Materials.

High-temperature lithiation is one of the crucial steps for the synthesis of Li- and Mn-rich layered metal oxide (LMLO) cathodes. A profound insight of the micromorphology and crystal structure evolution during calcination helps to realize the finely controlled preparation of final cathodes, finally achieving a desired electrochemical performance. In this work, two typical precursors (hydroxide and oxalate) were selected to prepare LMLO. It is found that the influence of the lithium source on reaction pathways is determined by the properties of precursors. In the case of hydroxide as a precursor, whatever lithium sources it is, the flake morphology of LMLO is inherited from hydroxide precursors. This is because the crystal structure of cathode products has a high similarity with its precursor in terms of the oxygen array arrangement, and the topological transformation occurs from hydroxide (P-3ml) to LMLOs (C/2m and R3m). Thus, the morphology and microstructure of LMLO cathodes could be well controlled only by tuning the properties of hydroxide precursors. Conversely, the decomposition of a lithium source has a great influence on the intermediate transformation when oxalate is used as the precursor. This is because a large amount of CO2 is released from the oxalate precursor after the decomposition reaction, resulting in drastic structural changes. At this time, the diffusion ability of the lithium source leads to the competition between the spinel phase and layered phase. Based on this point, the formation of a spinel intermediate phase can be reduced by accelerating the decomposition of the lithium source, contributing to the generation of a highly pure layered phase, thus exhibiting higher electrochemical performance. These insights provide an exciting cue to the rational selection and design of raw materials and lithium sources for the controlled synthesis of LMLO cathodes.

Life cycle assessment of an efficient biomass power plant supported by semi-closed supercritical CO2 cycle and chemical looping air separation.

Biomass power plant with carbon capture facility has great carbon emission reduction potential due to biomass's carbon neutrality characteristic, but it has been long-time suffered from undesirable system efficiency. This paper explored the life cycle carbon emission of a high-efficient biomass power generation system, which was comprised by the semi-closed supercritical CO2 cycle and chemical looping air separation sub-units. This system was proved to be environmentally superior with the life cycle warming impact value at 97.69 kg CO2 eq./MWh, the life cycle carbon emission reduction rate was 49.61 % and 45.46 % compared with traditional biomass gasification combined cycle system and biomass chemical looping gasification combined cycle system, respectively. The fuel and materials preparation stage should receive improvement attention due to its largest emission share of 76 %. In addition, the effects of key parameters, such as CO2 to biomass ratio (CO2/C), biomass gasification temperature, oxygen carrier and biomass types on environmental performance were investigated to further reveal this system's carbon emission reduction potential. The biomass/coal co-fired system showed net zero carbon emission was achieved when biomass share exceeded only around 10 %.

Evaluation of Compressive and Permeability Behaviors of Trabecular-Like Porous Structure with Mixed Porosity Based on Mechanical Topology.

The mechanical properties and permeability properties of artificial bone implants have high-level requirements. A method for the design of trabecular-like porous structure (TLPS) with mixed porosity is proposed based on the study of the mechanical and permeability characteristics of natural bone. With this technique, the morphology and density of internal porous structures can be adjusted, depending on the implantation requirements, to meet the mechanical and permeability requirements of natural bone. The design parameters mainly include the seed points, topology optimization coefficient, load value, irregularity, and scaling factor. Characteristic parameters primarily include porosity and pore size distribution. Statistical methods are used to analyze the relationship between design parameters and characteristic parameters for precise TLPS design and thereby provide a theoretical basis and guidance. TLPS scaffolds were prepared by selective laser melting technology. First, TLPS under different design parameters were analyzed using the finite element method and permeability simulation. The results were then verified by quasistatic compression and cell experiments. The scaling factor and topology optimization coefficient were found to largely affect the mechanical and permeability properties of the TLPS. The corresponding compressive strength reached 270-580 MPa; the elastic modulus ranged between 6.43 and 9.716 GPa, and permeability was 0.6 × 10-9-21 × 10-9; these results were better than the mechanical properties and permeability of natural bone. Thus, TLPS can effectively improve the success rate of bone implantation, which provides an effective theory and application basis for bone implantation.

Humanistic care interventions in patients with lower extremity arteriosclerosis obliterans.

OBJECTIVE: This study was designed to investigate the application value of humanistic care interventions in patients with lower extremity arteriosclerosis obliterans (LEASO). METHODS: We enrolled 98 LEASO patients undergoing interventional therapy in our hospital into this study, among whom 47 cases received conventional care interventions (the regular group) while the other 51 received humanistic care interventions based on conventional care interventions (the research group). The two groups were compared in negative emotions, complications, and quality of life of patients. RESULTS: Scores of negative emotions were lower in the research group than in the regular group after care (P < 0.05). The pain intensity decreased in both groups after care, with a sharper decrease in the research group (P < 0.05). The incidence of complications was lower in the research group than in the regular group after care (P < 0.05). The pain-free walking distance (PFWD) increased remarkably in both groups after care, with a longer PFWD in the research group than in the regular group (P < 0.05). Scores of the 36-Item Short-Form Health Survey (SF-36) increased after care in both groups (P < 0.05), with higher SF-36 scores in the research group than in the regular group (P < 0.05). SF-36 reflects the quality of life of patients from four aspects including vitality, emotional state, social function, and role-emotional. The care compliance and satisfaction level with care of patients were higher in the research group than in the regular group (P < 0.05). The care compliance rate and patient satisfaction level with care were higher in the research group than in the regular group (P < 0.05). CONCLUSION: Humanistic care interventions can reduce postoperative pain intensity and improve the quality of life in patients with LEASO.

New Technique Integrating Hydrate-Based Gas Separation and Chemical Absorption for the Sweetening of Natural Gas with High H2S and CO2 Contents.

Given the drawbacks of the traditional MDEA absorption process, we introduced a hydrate-based gas separation approach. Then, to study the effectiveness of this method, we performed some hydrating experiments demonstrating that energy consumption could be remarkably reduced. However, the acid components (H2S and CO2) in the product gas failed to meet the specification requirements of the sales gas. Consequently, a new technique was developed that integrated hydrate-based gas separation and chemical absorption for the sweetening of natural gas with high H2S and CO2 contents. To evaluate the performance of this new integrated method, technical comparisons based on simulation and experimental data were conducted. The results showed that the new integrated method could effectively remove sour components, which resulted in the product gas being able to meet the sales gas specifications. Additionally, the integrated technique consumed much less energy than the traditional MDEA absorption process and its amine regeneration duty was only 42% that of the MDEA method. What is more, upon an economical evaluation being performed, it was shown that the integrated technique tremendously reduced the investment and operating cost.

Hemoglobin-induced neuronal degeneration in the hippocampus after neonatal intraventricular hemorrhage.

Neuronal degeneration following neonatal intraventricular hemorrhage (IVH) is incompletely understood. Understanding the mechanisms of degeneration and cell loss may point toward specific treatments to limit injury. We evaluated the role of hemoglobin (Hb) in cell death after intraventricular injection in neonatal rats. Hb was injected into the right lateral ventricle of post-natal day 7 rats. Rats exposed to anesthesia were used for controls. The CA-1 region of the hippocampus was analyzed via immunohistochemistry, hematoxylin and eosin (H&E) staining, Fluoro-Jade C staining, Western blots, and double-labeling stains. Compared to controls, intraventricular injection of Hb decreased hippocampal volume (27% decrease; p<0.05), induced neuronal loss (31% loss; p<0.01), and increased neuronal degeneration (2.7 fold increase; p<0.01), which were all significantly reduced with the iron chelator, deferoxamine. Hb upregulated p-JNK (1.8 fold increase; p<0.05) and increased expression of the Hb/haptoglobin endocytotic receptor CD163 in neurons in vivo and in vitro (cultured cortical neurons). Hb induced expression of the CD163 receptor, which co-localized with p-JNK in hippocampal neurons, suggesting a potential pathway by which Hb enters the neuron to result in cell death. There were no differences in neuronal loss or degenerating neurons in Hb-injected animals that developed hydrocephalus versus those that did not. Intraventricular injection of Hb causes hippocampal neuronal degeneration and cell loss and increases brain p-JNK levels. p-JNK co-localized with the Hb/haptoglobin receptor CD163, suggesting a novel pathway by which Hb enters the neuron after IVH to result in cell death.

Susceptibility to intracerebral hemorrhage-induced brain injury segregates with low aerobic capacity in rats.

Although low exercise capacity is a risk factor for stroke, the exact mechanisms that underlie this connection are not known. As a model system for exploring the association between aerobic capacity and disease risks we applied two-way artificial selection over numerous generations in rats to produce low capacity runners (LCR) and high capacity runners (HCR). Here we compared intracerebral hemorrhage (ICH)-induced brain injury in both genders of these rat lines. HCR and LCR rats had 100µl blood injected into the right caudate and were killed at days 1, 3, 7 and 28 for brain water content determination, immunohistochemistry, histology, Western blot, and behavioral tests. Compared to male HCRs, male LCRs had more severe ICH-induced brain injury including worse brain edema, necroptosis, brain atrophy, and neurological deficits, but not increased numbers of Fluoro-Jade C positive cells or elevated cleaved caspase-3 levels. This was associated with greater microglial activation, and heme oxygenase-1 and protease activated receptor (PAR)-1 upregulation. In females, edema was also greater in LCRs than in HCRs, although it was less severe in females than in males for both LCRs and HCRs. Thus, ICH-induced brain injury was more severe in LCRs, a model of low exercise capacity, than in HCRs. Increased activation of microglia and PAR-1 may participate mechanistically in increased ICH-susceptibility. Females were protected against ICH-induced brain edema formation in both HCRs and LCRs.

Ischemic preconditioning attenuates brain edema after experimental intracerebral hemorrhage.

Ischemic preconditioning (IPC) provides protection against subsequent severe ischemic injury. A recent study found that cerebral IPC prolongs bleeding time. In this study, we examined whether IPC protects against intra-cerebral hemorrhage (ICH)-induced brain edema formation and whether IPC affects blood coagulation. There were three sets of experiments in this study. In the first set, male Sprague-Dawley rats were preconditioned with either 15 min of left middle cerebral artery occlusion, an IPC stimulus, or a sham operation. Three days later, rats received an infusion of autologous whole blood in the ipsilateral or contralateral caudate. Rats were killed 24 h later for brain water content measurement. In the second set, rats underwent 15 min of IPC or a sham operation. Three days later, rats were used for bleeding and thrombin clotting time tests. In the third set, the levels of p44/42 mitogen-activated protein kinases (MAPKs), heme oxygenase-1 (HO-1), transferrin (Tf), and transferrin receptor (TfR) in the brain 24 or 72 h after IPC were examined. We found that IPC reduced ICH-induced brain edema when blood was injected into the ipsilateral caudate but it did not when blood was injected into the contralateral caudate. IPC resulted in prolongation of bleeding time and thrombin clotting time. IPC also induced the activation of p44/42 MAPKs and upregulation of HO-1, Tf, and TfR levels in the ipsilateral caudate. These results suggest that IPC protects against ICH-induced brain edema formation and decreases blood coagulation. The protection of IPC against ICH is mainly due to local factors in the brain and may be related to activation of p44/42 MAPKs and upregulation of HO-1, Tf, and TfR.

Minocycline-induced attenuation of iron overload and brain injury after experimental intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Brain iron overload plays a detrimental role in brain injury after intracerebral hemorrhage (ICH). A recent study found that minocycline acts as an iron chelator and reduces iron-induced neuronal death in vitro. The present study investigated if minocycline reduces iron overload after ICH and iron-induced brain injury in vivo. METHODS: This study was divided into 4 parts: (1) rats with different sizes of ICH were euthanized 3 days later for serum total iron and brain edema determination; (2) rats had an ICH treated with minocycline or vehicle. Serum iron, brain iron, and brain iron handling proteins were measured; (3) rats had an intracaudate injection of saline, iron, iron+minocycline, or iron+macrophage/microglia inhibitory factor and were used for brain edema and neuronal death measurements; and (4) rats had an intracaudate injection of iron and were treated with minocycline. The brains were used for edema measurement. RESULTS: After ICH, serum total iron and brain nonheme iron increased and these changes were reduced by minocycline treatment. Minocycline also reduced ICH-induced upregulation of brain iron handling proteins and neuronal death. Intracaudate injection of iron caused brain edema, blood-brain barrier leakage, and brain cell death, all of which were significantly reduced by coinjection with minocycline. CONCLUSIONS: The current study found that minocycline reduces iron overload after ICH and iron-induced brain injury. It is also well known minocycline is an inhibitor of microglial activation. Minocycline may be very useful for patients with ICH because both iron accumulation and microglia activation contribute to brain damage after ICH.

Thrombin-induced autophagy: a potential role in intracerebral hemorrhage.

Autophagy occurs in the brain after intracerebral hemorrhage (ICH) and thrombin contributes to ICH-induced brain injury and cell death. In this study, we investigated whether thrombin may activate autophagy (in vivo and in cultured astrocytes) and its potential role in ICH. Autophagy was examined using electron microscopy, conversion of light chain 3(LC3) from the LC3-I form to LC3-II, cathepsin D Western blotting and monodansylcadaverine (MDC) staining to detect autophagic vacuoles. 3-Methyladenine (3-MA) was used as an autophagy inhibitor. In vivo, we found that intracaudate injection of thrombin increased conversion of LC3-I to LC3-II, cathepsin D levels, and formation of autophagic vacuoles in the ipsilateral basal ganglia. ICH-induced upregulation of LC3-I to LC3-II conversion and cathepsin D levels was reduced by a thrombin inhibitor, hirudin. In cultured astrocytes, thrombin enhanced the conversion of LC3-I to LC3-II and increased MDC-labeled autophagic vacuoles. 3-MA inhibited thrombin-induced autophagic vacuole formation and exacerbated thrombin-induced cell death. These results indicate that thrombin activates autophagy in the brain and that thrombin has a role in ICH-induced autophagy.

Effects of aging on autophagy after experimental intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) causes severe brain injury in aged rats. Autophagy occurs in the brain after ICH, and the present study examined the effects of aging on autophagy after ICH. Aged (18-22-month) and young (4-6-month) male Fischer rats received an intracerebral injection of 100-µL autologous whole blood. Rats were killed at day 7 for Western blot analysis to measure microtubule-associated protein light chain-3 (LC3), a biomarker of autophagosome, and cathepsin D, a lysosomal biomarker. Rats were killed at 11 weeks after ICH for brain histology. Age-related changes in neurological deficits were also examined. Western blotting showed that the LC3-I/LC3-II conversion ratio in the ipsilateral basal ganglia was higher in aged compared to young rats (p<0.05). Perihematomal cathepsin D levels were also higher in aged rats (p<0.05). Neurological deficits after ICH were more severe in aged rats, and they had a slower recovery of function (p<0.05). In addition, there were more ferritin and OX-42 positive cells in the ipsilateral basal ganglia in aged than in young rats 11 weeks after ICH (p<0.05). Brain atrophy was found in both young and aged rats. In conclusion, ICH causes more severe autophagy and neurological deficits in aged rats.

Iron accumulation and DNA damage in a pig model of intracerebral hemorrhage.

Cerebral iron overload causes brain injury after intracerebral hemorrhage (ICH) in rats and pigs. The current study examined whether an iron chelator, deferoxamine, can reduce ICH-induced DNA damage in pigs. Pigs received an injection of autologous blood into the right frontal lobe. Deferoxamine (50 mg/kg, i.m.) or vehicle was given 2 h after ICH and then every 12 h up to 7 days. Animals were killed at day 3 or day 7 after ICH to examine iron accumulation and DNA damage. We found that ICH resulted in the development of a reddish perihematomal zone, with iron accumulation and DNA damage within that zone. Deferoxamine treatment reduced the perihematomal reddish zone, and the number of Perls' (p<0.01) and TUNEL (p<0.01) positive cells. In conclusion, iron accumulates in the perihematomal zone and causes DNA damage. Systemic deferoxamine treatment reduces ICH-induced iron overload and DNA damage in pigs.

Hemoglobin expression in neurons and glia after intracerebral hemorrhage.

The purpose of this study was to examine the expression of hemoglobin (Hb) in the brain after intracerebral hemorrhage (ICH) and the effects of hemin and iron on neuronal Hb. For the in vivo studies, male Sprague-Dawley rats received either a sham operation or an ICH. The rats were killed 1, 4, 24 or 72 h later, and brains were used for real-time polymerase chain reaction (PCR) and immunohistochemistry. For the in vitro study, primary cultured neurons were exposed to either hemin or vehicle. Some neurons also received treatment with deferoxamine, an iron chelator. Neurons were collected 24 h later for real-time PCR. We found that α-globin (HbA) and ß-globin (HbB) mRNA levels in the ipsilateral basal ganglia are significantly increased after ICH, and Hb is localized in neurons and glia cells. Exposure of neurons to hemin also upregulated HbA and HbB mRNA levels. Hemin-induced HbA and HbB expression in cultured neurons was reduced by deferoxamine treatment. These results indicate that ICH increases HbA and HbB expression in neurons and glia cells, and that heme and iron may be important factors in inducing endogenous Hb expression after ICH.

Myeloid-specific deletion of the mineralocorticoid receptor reduces infarct volume and alters inflammation during cerebral ischemia.

BACKGROUND AND PURPOSE: mineralocorticoid receptor (MR) antagonists have protective effects in rodent models of ischemic stroke, but the cell type-specific actions of these drugs are unknown. In the present study, we examined the contribution of myeloid cell MR during focal cerebral ischemia using myeloid-specific MR knockout mice. METHODS: myeloid-specific MR knockout mice were subjected to transient (90 minutes) middle cerebral artery occlusion followed by 24 hours reperfusion (n=5 to 7 per group). Ischemic cerebral infarcts were identified by hematoxylin and eosin staining and quantified with image analysis software. Immunohistochemical localization of microglia and macrophages was performed using Iba1 staining, and the expression of inflammatory markers was measured after 24 hours of reperfusion by quantitative reverse transcription-polymerase chain reaction. RESULTS: myeloid-specific MR knockout resulted in a 65% reduction in infarct volume (P=0.005) after middle cerebral artery occlusion. This was accompanied by a significant reduction in activated microglia and macrophages in the ischemic core. Furthermore, myeloid-specific MR knockout suppressed classically activated M1 macrophage markers tumor necrosis factor-α, interleukin-1ß, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and interleukin-6 at the same time as partially preserving the induction of alternatively activated, M2, markers Arg1, and Ym1. CONCLUSIONS: these data demonstrate that myeloid MR activation exacerbates stroke and identify myeloid MR as a critical target for MR antagonists. Furthermore, these data indicate that MR activation has an important role in controlling immune cell function during the inflammatory response to stroke.

Tumor-targeted inhibition by a novel strategy - mimoretrovirus expressing siRNA targeting the Pokemon gene.

Pokemon gene has crucial but versatile functions in cell differentiation, proliferation and tumorigenesis. It is a master regulator of the ARF-HDM2-p53 and Rb-E2F pathways. The facts that the expression of Pokemon is essential for tumor formation and many kinds of tumors over-express the Pokemon gene make it an attractive target for therapeutic intervention for cancer treatment. In this study, we used an RNAi strategy to silence the Pokemon gene in a cervical cancer model. To address the issues involving tumor specific delivery and durable expression of siRNA, we applied the Arg-Gly-Asp (RGD) peptide ligand and polylysine (K(18)) fusion peptide to encapsulate a recombinant retrovirus plasmid expressing a siRNA targeting the Pokemon gene and produced the 'mimoretrovirus'. At charge ratio 2.0 of fusion peptide/plasmid, the mimoretrovirus formed stable and homogenous nanoparticles, and provided complete DNase I protection and complete gel retardation. This nanoparticle inhibited SiHa cell proliferation and invasion, while it promoted SiHa cell apoptosis. The binding of the nanoparticle to SiHa cells was mediated via the RGD-integrin α(v)ß(3) interaction, as evidenced by the finding that unconjugated RGD peptide inhibited this binding significantly. This tumor-targeting mimoretrovirus exhibited excellent anti-tumor capacity in vivo in a nude mouse model. Moreover, the mimoretrovirus inhibited tumor growth with a much higher efficiency than recombinant retrovirus expressing siRNA or the K(18)/P4 nanoparticle lacking the RGD peptide. Results suggest that the RNAi/RGD-based mimoretrovirus developed in this study represents a novel anti-tumor strategy that may be applicable to most research involving cancer therapy and, thus, has promising potential as a cervical cancer treatment.

Hemoglobin and iron handling in brain after subarachnoid hemorrhage and the effect of deferoxamine on early brain injury.

The purpose of this study was to investigate hemoglobin and iron handling after subarachnoid hemorrhage (SAH), examine the relationship between iron and neuroglial cell changes, and determine whether deferoxamine (DFX) can reduce SAH-induced injury. The SAH was induced in Sprague-Dawley rats (n=110) using an endovascular perforation technique. Animals were treated with DFX (100 mg/kg) or vehicle 2 and 6 hours after SAH induction followed by every 12 hours for 3 days. Rats were killed at 6 hours, Days 1 and 3 to determine nonheme iron and examine iron-handling proteins using Western blot and immunohistochemistry. 8-Hydroxyl-2'-deoxyguanosine and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining were performed to assess oxidative DNA damage and neuronal cell death. After SAH, marked heme-oxygenase-1 (HO-1) upregulation at Day 3 (P<0.01) was accompanied by elevated nonheme iron (P<0.01), transferrin (Tf) (P<0.01), Tf receptor (P<0.05), and ferritin levels (P<0.01). Deferoxamine treatment reduced SAH-induced mortality (12% versus 29%, P<0.05), brain nonheme iron concentration, iron-handling protein expression, oxidative stress, and neuronal cell death at Day 3 (P<0.01) after SAH. These results suggest that iron overload in the acute phase of SAH causes oxidative injury leading to neuronal cell death. Deferoxamine effectively reduced oxidative stress and neuronal cell death, and may be a potential therapeutic agent for SAH.

Brain alpha- and beta-globin expression after intracerebral hemorrhage.

Our recent study has demonstrated that hemoglobin (Hb) is present in cerebral neurons and neuronal Hb is inducible after cerebral ischemia. In the present study, we examined the effects of intracerebral hemorrhage (ICH) on the mRNA levels of the α-globin (HbA) and the ß-globin (HbB) components of Hb and Hb protein in the brain in vivo and in vitro. In vivo, male Sprague-Dawley rats received either a needle insertion (sham) or an infusion of autologous whole blood into the basal ganglia and were killed at different time points. In vitro, cultured rat brain cells were used for HbA, HbB and Hb determination. Cultured neurons were exposed to 50 or 100 µM hemin for 24 h. Some neurons also were treated with deferoxamine, an iron chelator, or vehicle. Levels of HbA and HbB, Hb and hemopexin, a transporter of heme, were measured. We found that HbA, HbB and Hb are primarily expressed in neurons, with much lower expression in astrocytes and microglia. HbA, HbB and Hb expression in the perihematomal zone was increased after ICH and Hb was localized in neurons and glia. Hemin increased HbA, HbB and hemopexin mRNA levels in cultured neurons. Deferoxamine reduced hemin-induced neuronal Hb expression. ICH increased HbA and HbB expression in the brain, which may potentially serve to buffer the heme released during clot resolution.

Activated autophagy pathway in experimental subarachnoid hemorrhage.

Recent results have suggested a role for autophagy in acute brain injury but an involvement in subarachnoid hemorrhage (SAH) has not been investigated. Although, autophagy is a regulated process essential for cellular homeostasis, it may represent an additional type of cell death mechanism. This study employed a modified endovascular perforation rat model under guidance by intracranial pressure monitoring to investigate whether autophagy pathway is involved in the early brain injury following SAH. Sham-operated control rats underwent an identical procedure without vessel perforation. Electron microscopy was performed to examine the ultrastructural changes in neural cells after SAH. Additionally, microtubule-associated protein light chain-3 (LC3), cathepsin-D and beclin-1 were investigated by Western blot analysis and immunohistochemistry. Electron microscopically, there was a marked increase in autophagosomes and autolysosomes in neurons at Day 1 following SAH. Although LC3 could be detected in sham-operated control rats, the conversion of LC3-I to LC3-II was significantly increased at Day 1 (P<0.01) and Day 3 (P<0.05). The time-course of beclin-1 expression paralleled the LC3 conversion. Cathepsin-D expression was also elevated at Day 1 (P<0.01). Immunohistochemical study with antibodies against cathepsin-D and beclin-1 showed numerous positive stained cells after SAH, especially in deep layers of the fronto-basal cortex. Double immunolabeling revealed beclin-1 expression predominantly in neurons. This present study showed that the autophagy pathway is activated in neurons in the acute phase after SAH.

Effects of cerebral ischemia on neuronal hemoglobin.

This study examined whether neuronal hemoglobin (Hb) is present in rats. It then examined whether cerebral ischemia or ischemic preconditioning (IPC) affects neuronal Hb levels in vivo and in vitro. In vivo, male Sprague-Dawley rats were subjected to either 15 mins of transient middle cerebral artery occlusion (MCAO) with 24 h of reperfusion, an IPC stimulus, or 24 h of permanent MCAO (pMCAO), or IPC followed 3 days later by 24 h of pMCAO. In vitro, primary cultured neurons were exposed to 2 h of oxygen-glucose deprivation (OGD) with 22 h of reoxygenation. Results showed that Hb is widely expressed in rat cerebral neurons but not astrocytes. Hemoglobin expression was significantly upregulated in the ipsilateral caudate and the cortical core of the middle cerebral artery territory after IPC. Hemoglobin levels also increased more in the penumbral cortex and the contralateral hemisphere 24 h after pMCAO, but expressions in the ipsilateral caudate and the cortical core area were decreased. Ischemic preconditioning modified pMCAO-induced brain Hb changes. Neuronal Hb levels in vitro were increased by 2 h of OGD and 22 h of reoxygenation. These results indicate that Hb is synthesized in neurons and can be upregulated by ischemia.

Blockade of EphB2 enhances neurogenesis in the subventricular zone and improves neurological function after cerebral cortical infarction in hypertensive rats.

EphB2/ephrinBs has been recently demonstrated to regulate cell proliferation in the neurogenic subventricular zone (SVZ). However, little is known about the role of EphB2 in adult neurogenesis following cerebral infarction. In the present study, we investigated the role of EphB2 in proliferation and differentiation of precursor cells within the SVZ, as well as the neurological function recovery after permanent middle cerebral artery occlusion (MCAO) in hypertensive rats. Bromodeoxyuridine (BrdU) was given twice per day starting from 24h after MCAO for 6-consecutive days. Recombinant EphB2-Fc or IgG-Fc was preclustered by incubation with anti-human Fcgamma and then intraventricularly administrated at 24h after MCAO. The neurological function was evaluated before operation and at 7, 14 and 21 days after MCAO respectively. The infarct size and immunoreactivities of BrdU, Nestin, DCX, GFAP and NeuN were measured at 7, 14 and 21 days after MCAO respectively. Treatment with EphB2-Fc markedly improved the neurological function recovery within 3 weeks after MCAO. In parallel, EphB2-Fc significantly increased the number of BrdU-labeled cells and led to marked increases in BrdU+/DCX+ and BrdU+/Nestin+ cells within the ipsilateral SVZ for 2 weeks after MCAO respectively (all p < 0.05). The BrdU+/NeuN+ cells in the peri-infarct area and neighboring ipsilateral striatum were significantly increased following EphB2-Fc infusion within 3 weeks after MCAO (all p < 0.05). Our data suggest that administration of exogenous clustered EphB2-Fc at 24h can enhance the endogenous neurogenesis and concomitantly improve neurological recovery after cerebral infarction.