Compensation for Electrode Detachment in Electrical Impedance Tomography with Wearable Textile Electrodes.

Electrical impedance tomography (EIT) is a radiation-free and noninvasive medical image reconstruction technique in which a current is injected and the reflected voltage is received through electrodes. EIT electrodes require good connection with the skin for data acquisition and image reconstruction. However, detached electrodes are a common occurrence and cause measurement errors in EIT clinical applications. To address these issues, in this study, we proposed a method for detecting faulty electrodes using the differential voltage value of the detached electrode in an EIT system. Additionally, we proposed the voltage-replace and voltage-shift methods to compensate for invalid data from the faulty electrodes. In this study, we present the simulation, experimental, and in vivo chest results of our proposed methods to verify and evaluate the feasibility of this approach.

Acoustic-Field Beamforming for Low-Power Portable Ultrasound.

Portable ultrasound has been extensively used for diagnostic applications in health monitoring, emergency rooms, and ambulances. However, these handheld ultrasound systems may suffer from heat and battery issues attributed to the large power consumption of the transmitter. Additionally, the largest portion of the direct current (DC) power consumption can be attributed to the amplifier in the digital-to-analog converter (DAC) of the transmitter and to the analog-to-digital converter (ADC) of the receiver. Therefore, the number of transmit/receive channels in a portable ultrasound instrument is one of the crucial design factors regarding heat and battery related issues. To address these problems, we propose an acoustic-field beamforming (AFB) technique for low-power portable ultrasound systems with a single receive and five transmit channels. Finally, the simulation, experimental, and in vivo results verified the feasibility of this approach.

Dry Wearable Textile Electrodes for Portable Electrical Impedance Tomography.

Electrical impedance tomography (EIT), a noninvasive and radiation-free medical imaging technique, has been used for continuous real-time regional lung aeration. However, adhesive electrodes could cause discomfort and increase the risk of skin injury during prolonged measurement. Additionally, the conductive gel between the electrodes and skin could evaporate in long-term usage and deteriorate the signal quality. To address these issues, in this work, textile electrodes integrated with a clothing belt are proposed to achieve EIT lung imaging along with a custom portable EIT system. The simulation and experimental results have verified the validity of the proposed portable EIT system. Furthermore, the imaging results of using the proposed textile electrodes were compared with commercial electrocardiogram electrodes to evaluate their performance.

DeepPPI: Boosting Prediction of Protein-Protein Interactions with Deep Neural Networks.

The complex language of eukaryotic gene expression remains incompletely understood. Despite the importance suggested by many proteins variants statistically associated with human disease, nearly all such variants have unknown mechanisms, for example, protein-protein interactions (PPIs). In this study, we address this challenge using a recent machine learning advance-deep neural networks (DNNs). We aim at improving the performance of PPIs prediction and propose a method called DeepPPI (Deep neural networks for Protein-Protein Interactions prediction), which employs deep neural networks to learn effectively the representations of proteins from common protein descriptors. The experimental results indicate that DeepPPI achieves superior performance on the test data set with an Accuracy of 92.50%, Precision of 94.38%, Recall of 90.56%, Specificity of 94.49%, Matthews Correlation Coefficient of 85.08% and Area Under the Curve of 97.43%, respectively. Extensive experiments show that DeepPPI can learn useful features of proteins pairs by a layer-wise abstraction, and thus achieves better prediction performance than existing methods. The source code of our approach can be available via http://ailab.ahu.edu.cn:8087/DeepPPI/index.html .

Analysis and Prediction of Exon Skipping Events from RNA-Seq with Sequence Information Using Rotation Forest.

In bioinformatics, exon skipping (ES) event prediction is an essential part of alternative splicing (AS) event analysis. Although many methods have been developed to predict ES events, a solution has yet to be found. In this study, given the limitations of machine learning algorithms with RNA-Seq data or genome sequences, a new feature, called RS (RNA-seq and sequence) features, was constructed. These features include RNA-Seq features derived from the RNA-Seq data and sequence features derived from genome sequences. We propose a novel Rotation Forest classifier to predict ES events with the RS features (RotaF-RSES). To validate the efficacy of RotaF-RSES, a dataset from two human tissues was used, and RotaF-RSES achieved an accuracy of 98.4%, a specificity of 99.2%, a sensitivity of 94.1%, and an area under the curve (AUC) of 98.6%. When compared to the other available methods, the results indicate that RotaF-RSES is efficient and can predict ES events with RS features.

Role for HIF-1α and Downstream Pathways in Regulating Neuronal Injury after Intracerebral Hemorrhage in Diabetes.

BACKGROUND/AIMS: HIF-1α is accumulated in the cellular nucleus and cytoplasm under conditions of oxygen deprivation and engaged in pathophysiologic changes of homeostasis by modulating the expression of several target genes. As an endogenous signaling protein, HIF-1α contributes to in neuroprotection, erythropoiesis, and apoptosis modulation. The purpose of this study was to examine the role played by HIF-1α in regulating neurological injury evoked by intracerebral hemorrhage (ICH) through its downstream product, namely vascular endothelial growth factor (VEGF). In particular, we examined the effects of diabetic hyperglycemia on HIF-1α response in the processing of ICH. METHODS: ELISA was used to measure HIF-1α and VEGF; and Western Blot analysis to examine the protein expression of VEGFR-2 and Caspase-3. Neurological Severity Score and brain water content were used to indicate neurological function and brain edema. RESULTS: HIF-1α and VEGF were significantly increased in the brain after induction of ICH in non-diabetic control rats and diabetic rats; however, the amplified levels of HIF-1α and VEGF were attenuated in diabetic rats (P<0.05 vs. non-diabetic rats) as compared with non-diabetic rats. Also, the protein expression of VEGF receptor subtype 2 was significantly less in the brain of diabetic rats (P<0.05 vs. non-diabetic rats). Further, cerebral infusion of HIF-1 activator stabilized VEGF levels, attenuated Caspase-3 and improved neurological deficits induced by ICH and the effects are smaller in diabetic animals. CONCLUSION: HIF-1α activated by ICH likely plays a beneficial role via VEGF mechanisms and response of HIF-1α is largely impaired in diabetes. This has pharmacological implications to target specific HIF-1α and VEGF pathway for neuronal dysfunction and vulnerability related to ICH.

Capillarisin Suppresses Lipopolysaccharide-Induced Inflammatory Mediators in BV2 Microglial Cells by Suppressing TLR4-Mediated NF-κB and MAPKs Signaling Pathway.

Capillarisin, one of the major bioactive compounds derived from Artemisia capillaries Thunb, has been reported to have extensive pharmacological properties, such as ant-inflammatory and anti-nociceptive activities. However, the molecular mechanisms responsible for the anti-inflammatory activity of capillarisin have not been elucidated in microglia. In the present study, we investigated the anti-inflammatory effects and molecular mechanisms of capillarisin on LPS-stimulated BV2 microglial cells. The effects of capillarisin on inflammatory mediators TNF-α, IL-6, IL-1ß, NO and PGE2 were detected. The effects of capillarisin on NF-κB and MAPK activation were detected by western blotting. The results showed that capillarisin suppressed LPS-induced TNF-α, IL-6, IL-1ß, NO and PGE2 production in a dose-dependent manner. Capillarisin also inhibited LPS-induced TLR4 expression, NF-κB and MAPKs activation in BV2 microglia. In conclusion, capillarisin inhibited LPS-induced inflammation by blocking TLR4-mediated NF-κB and MAPKs activation in BV2 microglia.

Metabolic Investigation on the Interaction Mechanism between Dietary Dihydrochalcone Intake and Lipid Peroxidation Product Acrolein Reduction.

SCOPE: Acrolein (ACR), a lipid peroxidation product, pathologically participates in various chronic diseases. In vitro evidence suggestes that dietary dihydrochalcones (DHCs) potentiate safe and alternative therapeutics to synthetic pharmaceuticals for ACR scavenging. Here, to investigate whether ingested DHCs could trap ACR and thereof result in reductions in endogenous ACR in mice is aimed. METHODS AND RESULTS: Three doses of phloretin (25, 100, and 400 mg kg-1 ), a major dietary DHC, are orally administrated to mice and 24 h urine and fecal samples are collected, respectively. High-resolution MS-based targeted metabolomics reveal for the first time that phloretin and its oxidized metabolite are able to trap endogenous ACR via formation of ACR conjugates. Quantification further demonstrate that a) more than 13% of ingested phloretin can dose-dependently trap 0.77-9.92 nmol of ACR within 24 h; b) phloretin ingestion leads to marked reductions in both free ACR and ACR metabolites in mouse urine compared to control; and c) trapping reactions by phloretin can account for up to 20.1% of the total decreases in endogenous ACR, depending on the administration doses. CONCLUSION: Findings from this study indicate that regular consumption of DHCs-rich diets holds great promise to alleviate the development of ACR-associated chronic diseases.

Influence of temperature gradient of slab track on the dynamic responses of the train-CRTS III slab track on subgrade nonlinear coupled system.

Temperature is an important load for ballastless track. However, there is little research on the system dynamic responses when a train travels on a ballastless track under the temperature gradient of ballastless track. Considering the moving train, temperature gradient of slab track, gravity of slab track, and the contact nonlinearity between interfaces of slab track, a dynamic model for a high-speed train runs along the CRTS III slab track on subgrade is developed by a nonlinear coupled way in ANSYS. The system dynamic responses under the temperature gradient of slab track with different amplitudes are theoretically investigated with the model. The results show that: (1) The proportions of the initial force and stress caused by the temperature gradient of slab track are different for different calculation items. The initial fastener tension force and positive slab bending stress have large proportions exceeding 50%. (2) The maximum dynamic responses for slab track are not uniform along the track. The maximum slab bending stress, slab acceleration, concrete base acceleration appear in the slab middle, at the slab end, and at the concrete base end, respectively. (3) The maximum accelerations of track components appear when the fifth or sixth wheel passes the measuring point, and at least two cars should be used. (4) The temperature gradient of slab track has a small influence on the car body acceleration. However, the influences on the slab acceleration, concrete base acceleration, fastener tension force are large, and the influence on the slab bending stress is huge.

Adenoviral transfer of hemopexin gene attenuates oxidative stress and apoptosis in cultured primary cortical neuron cell exposed to blood clot.

BACKGROUND: A growing body of experimental evidence suggests that hemin released from heme is a potent oxidant and accumulates in intracranial hematomas. Hemopexin (Hpx) decreases hemin accumulation and catabolism by nerve cells. In previous study, we observed that Hpx gene knockout aggravated striatal injury and worsened behavioral deficits of mice subjected to intracerebral hemorrhage. AIM: To examine the effect of Hpx on oxidative damage and apoptosis in cultured nerve cells with blood clot. METHODS: Neuron and glial cells were transfected with adenoviral Hpx gene. Transfected primary neuron-glial cells were co-cultured with 50 µl of arterial blood clot using insert transwells. The sham group was co-coulture with 50 µl of DMEM/F12, which contained 28 µl of serum; the control group was transfected with adenoviral vector. At 12 and 24 h, the level of malonaldehyde (MDA), surperoxide dismutase (SOD) concentration, glutathione (GSH), apoptosis, expression of HO-1 and caspase-3 were detected. RESULTS: MDA level was decreased (P < 0.01) whereas SOD and GSH concentration were increased in the Hpx group (P < 0.05 and P < 0.01, respectively). Results of flow cytometry revealed no significant difference in apoptosis between the Hpx group and model group at 12 h. However, the percentage of cells undergoing apoptosis in the Hpx group was decreased at 24 h compared with the model group (P < 0.01). HO-1 expression decreased in the Hpx group at 24 h (P < 0.01) while caspase-3 expression decreased at both 12 and 24 h (P < 0.011 and P < 0.05, respectively) compared with the model group. CONCLUSION: Hpx protected nerve cells exposed to blood from injury by anti-oxidation and a decrease in the expression of HO-1 and caspase-3.

A double-injection model of intracerebral hemorrhage in rabbits.

We aimed to develop a double-injection model of intracerebral hemorrhage (ICH) in rabbits and to evaluate it as a tool for investigating post-ICH brain injury. Rabbits were injected with 300microL fresh autologous whole blood into the right basal ganglia. Behavioral changes were rated, brain water content (BWC) was measured and brain tissue morphology was also examined. ICH was established in 93.5% of the blood injection group. At 1, 3 and 7 days after ICH, there were significant differences in the total neurological scores (p<0.01) and BWC (p<0.01) between a sham-operated group and the ICH group. These findings suggest that the model produces a persistent neurological deficit, hematoma volume and perihematomal edema and closely mimics human hypertensive basal ganglia ICH; it is a controllable and reproducible hematoma that lends itself to quantitative investigation.

[Therapeutic effect of hypoxia-inducible factor-1alpha on focal cerebral ischemia: experiment with rats].

OBJECTIVE: To construct a recombinant adenoviral vector carrying HIF-1alpha gene and explore the therapeutic effect of HIF-1alpha on focal cerebral ischemia in adult rats. METHODS: The AdEasy System was used to construct the recombinant adenoviral vector carrying HIF-1alpha gene and green fluorescent protein and PCR was used to identify the HIF-1alpha gene. Middle cerebral artery occlusion (MCAo) and reperfusion models were established and divided into Ad-HIF-1alpha group, Ad group and NS group. After Ad-HIF-1alpha, Ad and NS were injected into the ischemic ventricle, expression of Ad-HIF-1alpha was observed and its therapeutic effect was evaluated by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining and neurological severity scores. RESULTS: GFP expression distributed apart from the ventricle and reached a peak at 14 days and persisted for about 4 weeks under fluorescent microscope. The neurological severity scores was 2.4 +/- 0.5 at 24 h in Ad-HIF-1alpha group and there was no statistical significance compared with Ad group (2.6 +/- 0.5) and NS group (2.7 +/- 0.7) (P > 0.05). The scores were 1.6 +/- 0.7 at 48 h and 0.9 +/- 0.6 at 72 h in Ad-HIF-1alpha group, and there were statistical significance compared with Ad group (2.9 +/- 0.6 and 3.2 +/- 0.6 respectively) and NS group (3.0 +/- 0.7 and 3.2 +/- 0.8) (P < 0.05). The infarct volume was 81.2 mm(3) +/- 1.4 mm(3) at 72 h in Ad-HIF-1alpha group and there was statistical significance compared with Ad group (173.9 mm(3) +/- 1.3 mm(3)) and NS group (171.7 mm(3) +/- 6.2 mm(3)) (P < 0.05). CONCLUSION: HIF-1alpha gene had definite therapeutic effect on focal cerebral ischemia in adult rats, which settles a foundation for next HIF-1alpha gene study and clinic application.

Prediction of protein-protein interaction sites by means of ensemble learning and weighted feature descriptor.

BACKGROUND: Reliable prediction of protein-protein interaction sites is an important goal in the field of bioinformatics. Many computational methods have been explored for the large-scale prediction of protein-protein interaction sites based on various data types, including protein sequence, structural and genomic data. Although much progress has been achieved in recent years, the problem has not yet been satisfactorily solved. RESULTS: In this work, we presented an efficient approach that uses ensemble learning algorithm with weighted feature descriptor (EL-WFD) to predict protein-protein interaction sites. Moreover, weighted feature descriptor was designed to describe the distance influence of neighboring residues on interaction sites. The results on two dataset (Hetero and Homo), show that the proposed method yields a satisfactory accuracy with 83.8 % recall and 96.3 % precision on the Hetero dataset and 84.2 % recall and 96.3 % precision on the Homo dataset, respectively. In both datasets, our method tend to obtain high Mathews correlation coefficient compared with state-of-the-art technique random forest method. CONCLUSIONS: The experimental results show that the EL-WFD method is quite effective in predicting protein-protein interaction sites. The novel weighted feature descriptor was proved to be promising in discovering interaction sites. Overall, the proposed method can be considered as a new powerful tool for predicting protein-protein interaction sites with excellence performance.

[Study in the mechanism of Shuxuetong injection on antithrombosis and thrombolysis].

OBJECTIVE: To study the effect of Shuxuetong injection on cerebral tissue and brain microvascular endothelial cell(BMEC) in secreting tissue-type plasminogen activator (tPA). METHOD: The experiment in vivo was designed for three groups: sham-operation group, focal cerebral ischemia model group, Shuxuetong injection-treated group. The gene expression and the activity of tPA on brains were detected by RT-PCR and chromogenic substrate analysis respectively after treatment for five days; The experiment in vitro: The cultured BMEC were divided into experimental group and control group. The Shuxuetong injection were added into experimental group and the BMECs in the experimatal groups were treated for 24 h. The gene expression and the activity of tPA on cultured BMEC were detected by RT-PCR and chromogenic substrate analysis respectively. RESULT: The gene expression and the content of tPA on both cerebral tissue and BMEC in the experimatal groups were significantly higher than that in the control groups. CONCLUSION: Shuxuetong injection could accelerate secretion of tPA, and therefore enhance fibrinolysis.

Resveratrol ameliorates oxidative stress and inhibits aquaporin 4 expression following rat cerebral ischemia-reperfusion injury.

Cerebral ischemia-reperfusion (I/R) is associated with increased levels of reactive oxygen species (ROS) and brain edema, which lead to the deterioration of patient prognosis. Resveratrol serves a neuroprotective role in I/R injury, and this role may be associated with its anti­oxidative effects. However, resveratrol's mechanism of action in cerebral I/R injury remains to be fully understood. In order to investigate the effect of resveratrol in cerebral I/R­induced injury, male Sprague­Dawley rats were randomly assigned to four groups: The sham­operation group, the I/R group and the edaravone and resveratrol groups (I/R + E and I/R + R groups). Infarct volume was evaluated by 2,3,5­tripenyltetrazolium chloride staining, brain edema was evaluated by the water content in the reperfused brain and malondialdehyde (MDA) was measured by the thiobarbituric acid method. Superoxide dismutase (SOD) levels were measured using the Total Superoxide Dismutase Assay kit. Inducible nitric oxide synthase (iNOS) levels in the hippocampus and cortex were measured by ELISA, and aquaporin 4 (AQP4) expression was measured by immunohistochemical staining and western blot analysis. The results demonstrated that resveratrol reduced the infarct volume and the incidence of brain edema and reduced neurological deficits. These outcomes were accompanied by reduced levels of MDA, iNOS and AQP4, and increased SOD levels in cerebral I/R injury. In conclusion, resveratrol protected against cerebral I/R injury by ameliorating oxidative stress and reducing AQP4 expression.

Inhibition of endothelin A receptor protects brain microvascular endothelial cells against hypoxia­induced injury.

Endothelin-1 (ET-1)-induced cell damage is commonly involved in ischemia/hypoxia-associated diseases. PD155080 [sodium 2-benzo (1.3)dioxol-5-yl-3-benzyl-4-(4­metho-xyphenyl)-4-oxobut-2-enoate] is a selective endothelin A receptor (ETAR) antagonist that inhibits ET-1­induced cell damage. The aim of this study was to investigate the effects of PD155080 on hypoxia-induced rat brain microvascular endothelial cell (BMEC) injury. BMECs were isolated from the cerebral cortex of Wistar rats and cultured in an anoxia chamber, containing 95% N(2) and 5% CO(2) for 12 h. BMEC injury was assessed by determining cellular ultra-microstructural changes and cell viability by MTT assay, trypan blue (TB) staining and measuring the lactate dehydrogenase (LDH) levels. ET-1 mRNA expression was detected by in situ hybridization and reverse transcription PCR (RT-PCR); the ET-1 protein level was measured by radioimmunoassay. Following exposure to hypoxic conditions, the viability of the BMECs was markedly decreased and the ultrastructure of the BMECs was damaged, as demonstrated by chromatin margination, chromatin agglutination, plasma edema, the increased number of intracellular liposomes and vacuoles, mitochondrial swelling and the expansion of a rough surfaced endoplasmic reticulum. The levels of ET-1 and ET-1 mRNA expression in the BMECs were increased following exposure to hypoxic conditions. Of note, the administration of PD155080 greatly enhanced the viability of the BMECs and ameliorated hypoxia-induced cellular injury. PD155080 also inhibited hypoxia-induced ET-1 production by the BMECs. In conclusion, PD155080 exerts protective effects against hypoxia-induced BMEC injury.

Associations of matrix metalloproteinase-9 and monocyte chemoattractant protein-1 concentrations with carotid atherosclerosis, based on measurements of plaque and intima-media thickness.

PURPOSE: To examine associations of matrix metalloproteinase-9 (MMP-9) and monocyte chemoattractant protein-1 (MCP-1) concentrations with the severity of carotid atherosclerosis, based on measurements of carotid plaque and intima-media thickness (IMT). METHODS: This cross-sectional study included 116 stroke-free participants (45.7% males, 54.3% females; mean age, 64.73 ± 14.53 years). Serum MMP-9 and MCP-1 concentrations were measured, and plaque morphology, including total plaque score (PS), plaque stability, and IMT, was assessed ultrasonographically. Participants were grouped according to total PS (0, 1-2, ≥ 3), plaque stability (no plaque, stable, unstable) and IMT tertiles (<0.8 mm, 0.8-1 mm, >1 mm). Multinomial logistic regression models were used to assess the associations of MMP-9 and MCP-1 concentrations with plaque and IMT values after adjusting for vascular risk factors. RESULTS: MMP-9 quartiles (vs. quartile 1) were significantly associated with a greater prevalence of plaque instability [Q2: odds ratio (OR) = 5.13, 95% confidence interval (CI) = 1.01-24.9, p = 0.042; Q3: OR = 15.5, 95% CI = 3.1-78.1, p = 0.001; Q4: OR = 13.2, 95% CI = 2.7-64.97, p = 0.001] and high total PS (Q3: OR = 10.02, 95% CI = 1.5-65.33, p = 0.016; Q4: OR = 21.5, 95% CI = 3.5-132.1, p = 0.001). MCP-1 concentration was significantly associated with IMT (OR = 22.94, 95% CI = 2.14-245.66, p = 0.01). CONCLUSIONS: Elevated serum MMP-9 concentration was independently associated with high total carotid artery PS, plaque instability, and large IMT value. MCP-1 concentration was independently associated with IMT, but not with plaque morphology.

Meta-analysis comparing deep brain stimulation of the globus pallidus and subthalamic nucleus to treat advanced Parkinson disease.

OBJECT: Deep brain stimulation (DBS) is the surgical procedure of choice for patients with advanced Parkinson disease (PD). The globus pallidus internus (GPi) and the subthalamic nucleus (STN) are commonly targeted by this procedure. The purpose of this meta-analysis was to compare the efficacy of DBS in each region. METHODS: MEDLINE/PubMed, EMBASE, Web of Knowledge, and the Cochrane Library were searched for English-language studies published before April 2013. RESULTS: of studies investigating the efficacy and clinical outcomes of DBS of the GPi and STN for PD were analyzed. RESULTS: Six eligible trials containing a total of 563 patients were included in the analysis. Deep brain stimulation of the GPi or STN equally improved motor function, measured by the Unified Parkinson's Disease Rating Scale Section III (UPDRSIII) (motor section, for patients in on- and off-medication phases), within 1 year postsurgery. The change score for the on-medication phase was 0.68 (95% CI - 2.12 to 3.47, p > 0.05; 5 studies, 518 patients) and for the off-medication phase was 1.83 (95% CI - 3.12 to 6.77, p > 0.05; 5 studies, 518 patients). The UPDRS Section II (activities of daily living) scores for patients on medication improved equally in both DBS groups (p = 0.97). STN DBS allowed medication dosages to be reduced more than GPi DBS (95% CI 129.27-316.64, p < 0.00001; 5 studies, 540 patients). Psychiatric symptoms, measured by Beck Depression Inventory, 2nd edition scores, showed greater improvement from baseline after GPi DBS than after STN DBS (standardized mean difference -2.28, 95% CI -3.73 to -0.84, p = 0.002; 3 studies, 382 patients). CONCLUSIONS: GPi and STN DBS improve motor function and activities of daily living for PD patients. Differences in therapeutic efficacy for PD were not observed between the 2 procedures. STN DBS allowed greater reduction in medication for patients, whereas GPi DBS provided greater relief from psychiatric symptoms. An understanding of other symptomatic aspects of targeting each region and long-term observations on therapeutic effects are needed.

Effects of recombinant adenovirus-mediated hypoxia-inducible factor-1alpha gene on proliferation and differentiation of endogenous neural stem cells in rats following intracerebral hemorrhage.

OBJECTIVE: To investigate the effects of adenovirus (Ad)-mediated hypoxia-inducible factor-1alpha (HIF-1α) gene on proliferation and differentiation of endogenous neural stem cells (NSCs) in rats following intracerebral hemorrhage (ICH) and the underlying mechanisms. METHODS: A total of 120 specific pathogen-free, adult, male Sprague-Dawley rats were included in this study. After establishment of ICH models in rats, PBS, Ad, or Ad-HIF-1α was administered via the ischemic ventricle. On the 1st, 7th, 14th, 21st and 28th d after ICH, rat neurological deficits were scored, doublecortin (DCX) expression in the subventricular zone cells was detected by immunohistochemical staining, and 5-bromo-2'-deoxyuridine (BrdU)-, BrdU/DCX-, and BrdU/glial fibrillary acidic protein-positive cells in the subventricular zone were counted using immumofluorescence method among PBS, Ad, and Ad-HIF-1α groups. RESULTS: On the 7th, 14th, 21st and 28th d after ICH, neurological deficit scores in the Ad-HIF-1α group were significantly lower than in the PBS and Ad groups (P<0.05). In the Ad-HIF-1α group, DCX expression was significantly increased on the 7th d, peaked on the 14th d, and then gradually decreased. In the Ad-HIF-1α group, BrdU-positive cells were significantly increased over time course, and significant difference in BrdU-positive cell counts was observed when compared with the PBS and Ad groups at each time point (P<0.01 or 0.05). On the 7th, 14th, 21st and 28th d after ICH, the number of DCX-, BrdU-, BrdU/DCX-, and BrdU/DCX-positive cells in the Ad-HIF-1α group was significantly greater than in the PBS and Ad groups (P<0.05). CONCLUSIONS: HIF-1α gene can promote the proliferation, migration and differentiation of endogenous neural stem cells after ICH, thereby contributing to neurofunctional recovery after ICH.

Erythropoietin reduces brain injury after intracerebral hemorrhagic stroke in rats.

Erythropoietin (EPO) has been shown to be neuroprotective in various models of neuronal injury. The aim of the present study was to investigate the beneficial effect of recombinant human EPO (rhEPO) following intracerebral hemorrhage (ICH) and the underlying molecular and cellular mechanisms. ICH was induced using autologous blood injection in adult rats. rhEPO (5000 IU/kg) or vehicle was administered to rats with ICH 2 h following surgery and every 24 h for 1 or 3 days. To study the involvement of the PI3K signaling pathway in the rhEPO­mediated effect, the PI3K inhibitor wortmannin (15 µg/kg), was intravenously administered to rats with ICH 90 min prior to rhEPO treatment. Brain edema was measured 3 days following ICH and behavioral outcomes were measured at 1, 7, 14, 21 and 28 days following ICH using the modified neurological severity score (mNSS) and the corner turn test. Proinflammatory cytokines, including tumor necrosis factor (TNF)­α, interleukin (IL)-1ß and IL-6, in the ipsilateral striatum were analyzed using an enzyme-linked immunosorbent assay 24 h following ICH. Neuronal apoptosis in the perihematomal area was determined by NeuN and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) double-staining. The results showed that rhEPO treatment reversed ICH, increased brain water content, upregulated proinflammatory cytokines, neuronal loss and apoptosis in the perihematomal area and rescued behavioral deficits in injured rats. Inhibiting the PI3K pathway with wortmannin abolished the rhEPO­mediated neuroprotective effects. Moreover, western blot analysis showed that rhEPO induced the upregulation of Akt phosphorylation and downregulation of glycogen synthase kinase (GSK)­3ß phosphorylation, which were reversed by pretreatment with wortmannin, indicating the involvement of PI3K signaling in rhEPO-mediated anti-apoptotic and anti-inflammatory effects following ICH. In conclusion, these results suggested that rhEPO may exert its beneficial effects in ICH through the activation of the PI3K signaling pathway.