Repression of the Antioxidant NRF2 Pathway in Premature Aging.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare, invariably fatal premature aging disorder. The disease is caused by constitutive production of progerin, a mutant form of the nuclear architectural protein lamin A, leading, through unknown mechanisms, to diverse morphological, epigenetic, and genomic damage and to mesenchymal stem cell (MSC) attrition in vivo. Using a high-throughput siRNA screen, we identify the NRF2 antioxidant pathway as a driver mechanism in HGPS. Progerin sequesters NRF2 and thereby causes its subnuclear mislocalization, resulting in impaired NRF2 transcriptional activity and consequently increased chronic oxidative stress. Suppressed NRF2 activity or increased oxidative stress is sufficient to recapitulate HGPS aging defects, whereas reactivation of NRF2 activity in HGPS patient cells reverses progerin-associated nuclear aging defects and restores in vivo viability of MSCs in an animal model. These findings identify repression of the NRF2-mediated antioxidative response as a key contributor to the premature aging phenotype.

A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A.

Sirtuin 6 (SIRT6) is a deacylase and mono-ADP ribosyl transferase (mADPr) enzyme involved in multiple cellular pathways implicated in aging and metabolism regulation. Targeted sequencing of SIRT6 locus in a population of 450 Ashkenazi Jewish (AJ) centenarians and 550 AJ individuals without a family history of exceptional longevity identified enrichment of a SIRT6 allele containing two linked substitutions (N308K/A313S) in centenarians compared with AJ control individuals. Characterization of this SIRT6 allele (centSIRT6) demonstrated it to be a stronger suppressor of LINE1 retrotransposons, confer enhanced stimulation of DNA double-strand break repair, and more robustly kill cancer cells compared with wild-type SIRT6. Surprisingly, centSIRT6 displayed weaker deacetylase activity, but stronger mADPr activity, over a range of NAD+ concentrations and substrates. Additionally, centSIRT6 displayed a stronger interaction with Lamin A/C (LMNA), which was correlated with enhanced ribosylation of LMNA. Our results suggest that enhanced SIRT6 function contributes to human longevity by improving genome maintenance via increased mADPr activity and enhanced interaction with LMNA.

Mechanochromic Hydrogel Fibers with Multiple Fluorescent Colors.

Mechanochromic polymers can change their color in response to external force and have shown promising applications in stress sensing and failure warning. They are usually obtained as thin films or bulky specimens. The mechanochromic fibers, which can be used to make smart fabrics, have been seldom reported due to the lack of efficient fabrication techniques. In this work, a general method using photo-polymerization of microgel solution in a template tube to produce mechanochromic hydrogel fibers is reported. The obtained hydrogel fibers can generate visible and fluorescent color changes upon deformation. The diameter of the mechanochromic fibers can be easily adjusted by using different template tubes. The mechanochromic fibers can be fabricated as long as 1 m. By reducing the fiber diameter or increasing the microgel concentration, the mechanical properties of the mechanochromic fibers can be improved, leading to more obvious mechanochromic behavior. The polymethacrylate (PMA) is further used to coat the hydrogel fibers, prevent the loss of water in the fibers, and increase the storage time. The mechanochromic fibers with multiple fluorescent colors are further fabricated by utilizing different microgel solutions. This work provides an easy and effective method to fabricate mechanochromic fibers with different color change abilities.

Research on a Corrosion Detection Method for Oil Tank Bottoms Based on Acoustic Emission Technology.

This paper presents an acoustic emission (AE) detection method for refined oil storage tanks which is aimed towards specialized places such as oil storage tanks with high explosion-proof requirements, such as cave oil tanks and buried oil tanks. The method utilizes an explosion-proof acoustic emission instrument to detect the floor of a refined oil storage tank. By calculating the time difference between the defective acoustic signal and the speed of acoustic wave transmission, a mathematical model is constructed to analyze the detected signals. An independent channel AE detection system is designed, which can store the collected data in a piece of independent explosion-proof equipment, and can analyze and process the data in a safe area after the detection, solving the problems of a short signal acquisition distance and the weak safety protection applied to traditional AE instruments. A location analysis of the AE sources is conducted on the bottom plate of the tank, evaluating its corrosion condition accurately. The consistency between the evaluation and subsequent open-tank tests confirms that using AE technology effectively captures corrosion signals from oil storage tanks' bottoms. The feasibility of carrying out online inspection under the condition of oil storage in vertical steel oil tanks was verified through a comparison with open inspections, which provided a guide for determining the inspection target and opening order of large-scale oil tanks.

Associations among Parental Phubbing, Self-esteem, and Adolescents' Proactive and Reactive Aggression: A Three-Year Longitudinal Study in China.

Parental phubbing, as a new risk factor for adolescents' healthy development, has been noticed by scholars. However, few studies have clarified the associations between parental phubbing and adolescents' proactive and reactive aggression and the potential mediating mechanisms. To address the gaps, the current study explored the longitudinal associations among parental phubbing, self-esteem, and adolescents' proactive and reactive aggression by using the parallel process latent growth curve model and the cross-lagged panel model. The current study involved 2407 Chinese adolescents (girls were 1202, Mage = 12.75, SD = 0.58 at baseline, range = 11-16). Results indicated that parental phubbing significantly positively predicted adolescents' reactive aggression but not proactive aggression. Self-esteem significantly predicted the adolescents' reactive and proactive aggression. Self-esteem significantly mediated the associations between parental phubbing and adolescents' proactive and reactive aggression, respectively. These findings suggest that intervening with parental phubbing is a promising way to reduce adolescents' reactive aggression, and promoting adolescents' self-esteem is an effective approach to prevent their proactive and reactive aggression.

Antibiotic resistance genes in gut of breast-fed neonates born by caesarean section originate from breast milk and hospital ward air.

The human gut is a reservoir of antibiotic resistance genes (ARGs). Even in the absence of antibiotics, ARGs are present in large quantities in faeces of adults, children and even newborns. However, where and when ARGs are acquired remains unclear, as does the types of ARGs acquired. Herein, we recruited 82 pairs of women and their caesarean section newborns. Conventional culture methods and quantitative PCR were employed to detect nine species and six ARG types in meconia, faeces from 3-day-old newborns, amniotic fluid, colostrum, and hospital ward air samples. Furthermore, ARG transfer was explored by tracking Staphylococcus epidermidis isolated from faeces of 3-day-old newborns, colostrum and ward air samples using multi-locus sequence typing (MLST). No ARGs or microorganisms were detected in meconia or amniotic fluid. One or more ARGs were detected in 90.2% of faeces from 3-day-old newborns, and the mecA gene exhibited the highest detection rate (45.1%). ARGs were detected in 85.4% of colostra consistent with ARGs in faeces from 3-day-old newborns. Some ARGs were detected in ward air, and might also be a source of ARGs in neonatal faeces. Isolation of S. epidermidis from neonatal faeces was consistent with antibiotic resistance and gene profiles for colostrum samples. Traceability analysis of S. epidermidis showed that ARGs in neonatal faeces mainly originated from colostrum, and partly from ward air. After birth, neonates born by caesarean section obtain a variety of ARGs mainly from colostrum, and partly from ward air.

Large-scale DNA barcoding of the subfamily Culterinae (Cypriniformes: Xenocyprididae) in East Asia unveils a geographical scale effect, taxonomic warnings and cryptic diversity.

Geographical scale might be expected to impact significantly the efficiency of DNA barcoding as spatially comprehensive sampling provides opportunities to uncover intricate relationships among closely related species and to detect cryptic diversity for widespread taxa. Here, we present a DNA barcoding study on a Xencyprididae subfamily (Culterinae) involving the production of 998 newly generated DNA barcodes from East Asian drainages (80 localities). Together with 513 barcodes mined from BOLD and GenBank, a reference library consisting of 1511 DNA barcodes (116 localities) for 42 species was assembled, accounting for 66% of known Culterinae species. Intraspecific genetic distances are positively correlated to geographical scale, while a negative correlation is detected between interspecific genetic distances and geographical scale. The present study demonstrates that geographical scale influences the efficiency of DNA barcoding by narrowing the width of the barcoding gap. DNA-based species delimitation analyses delimited 44 molecular operational taxonomic units (MOTUs). Rampant cryptic diversity is detected within eight species with multiple MOTUs, whereas 25 species present mismatch between morphological and molecular delimitations. A total of 18 species are lumped into nine MOTUs due to low interspecific divergence and/or mixed lineages. Several MOTU divergences are hypothesized to relate to known biogeographical barriers and geological events during the Pliocene and Pleistocene. This study provides new insights into the taxonomy and phylogeography of the subfamily Culterinae.

Hybrid Phenol-Rhodamine Dye Based Mechanochromic Double Network Hydrogels with Tunable Stress Sensitivity.

Mechanochromic hydrogels, which can switch their color in response to the applied external force, have shown great potential in stress visualization and damage indication. However, the kinds of colors in the reported mechanochromic hydrogels are limited. It is challenging to develop mechanochromic hydrogels with new kinds of color changes. Herein, a kind of mechanochromic double network (DN) hydrogel is reported based on the hybrid phenol-rhodamine mechanophore. The hydrogels turn into orange color with an emission wavelength of around 566/574 nm in response to tensile and compressive stress. The DN hydrogels show great reversibility. The color of DN hydrogels vanishes slowly after releasing the stress. The stress sensitivity can be tailored by the crosslinking density and the mechanophore concentration of the first network. In addition, the influence of the pH on the mechanochromic properties of DN hydrogels is also studied. This study provides an insightful study in tuning the stress sensitivity in the mechanochromic hydrogel, which will be beneficial for the development of mechanochromic materials.

Modulation of vascular integrity and neuroinflammation by peroxiredoxin 4 following cerebral ischemia-reperfusion injury.

Ischemic stroke is a leading cause of morbidity and mortality worldwide, with oxidative stress playing a key role in the injury mechanism of thrombolytic therapy. There is increasing evidence that oxidative stress damages endothelial cells (ECs), degrades tight junction proteins (TJs), and contributes to increased blood-brain barrier (BBB) permeability. It has been demonstrated that the breakdown of BBB could increase the risk of intracerebral hemorrhagic transformation in ischemic stroke. And an episode of cerebral ischemia/reperfusion (I/R) also initiates oxidative stress-mediated inflammatory processes in ECs, which further promotes BBB disruption and the progression of brain injury. Previous studies have revealed that antioxidants could inhibit ROS generation and attenuate BBB disruption after cerebral I/R. Peroxiredoxin 4 (Prx4) is a member of the antioxidant enzymes family (Prx1-6) and has been characterized to be an efficient H2O2 scavenger. It should be noted that Prx4 may be directly involved in the protection of ECs from the effects of ROS and function in ECs as a membrane-associated peroxidase. This paper reviewed the implication of Prx4 on vascular integrity and neuroinflammation following a cerebral I/R injury.

Insight into the combinatorial transcriptional regulation on α-amylase gene in animal groups with different dietary nutrient content.

Gene expression is generally regulated by multiple transcription factors (TFs). Despite previous findings of individual TFs regulating pancreatic α-amylase gene expression, the combinatorial transcriptional regulation is not fully understood. To gain insight into multiple TF regulation for pancreatic α-amylase gene, we employed a function conservation approach to predict interacting TFs regulating pancreatic α-amylase gene for 3 dietary animal groups. To this end, we have identified 77, 25, and 118 interacting TFs for herbivore, omnivore, and carnivore, respectively. Computational modeling of TF regulatory networks demonstrated that known pancreas-specific TFs (e.g. GR, NFAT, and PR) may play important roles in recruiting non pancreas-specific TFs to the TF-TF interaction networks, offering specificity and flexibility for controlling pancreatic α-amylase gene expression in different dietary animal groups. The findings from this study indicate that combinatorial transcriptional regulation could be a critical component controlling pancreatic α-amylase gene expression.

Performance of Portfolios Based on the Expected Utility-Entropy Fund Rating Approach.

Yang and Qiu proposed and reframed an expected utility-entropy (EU-E) based decision model. Later on, a similar numerical representation for a risky choice was axiomatically developed by Luce et al. under the condition of segregation. Recently, we established a fund rating approach based on the EU-E decision model and Morningstar ratings. In this paper, we apply the approach to US mutual funds and construct portfolios using the best rating funds. Furthermore, we evaluate the performance of the fund ratings based on the EU-E decision model against Morningstar ratings by examining the performance of the three models in portfolio selection. The conclusions show that portfolios constructed using the ratings based on the EU-E models with moderate tradeoff coefficients perform better than those constructed using Morningstar. The conclusion is robust to different rebalancing intervals.

Activation of NADPH/ROS pathway contributes to angiogenesis through JNK signaling in brain endothelial cells.

Recent evidences have shown that reactive oxygen species (ROS) are involved in regulating angiogenesis and preventing tissue injury. However, the precise molecular mechanisms behind ROS-induced angiogenesis are still unknown. The aim of the present study was to investigate the effects of ROS-induced angiogenesis in rat brain microvessel endothelial cells (rBMECs) and identify involving the signal pathways. For initial experiments, the rBMECs were incubated with different concentrations of hydrogen peroxide (H2O2). For the second experiments, the rBMECs were respectively treated with ROS scavenger dimethylthiourea (DMTU), NADPH oxidase (Nox) inhibitor apocynin, small interfering RNAs-mediated knock down Nox2 or Nox4, or pretreated with c-Jun N-terminal kinase (JNK) inhibitor SP600125. The cell proliferation, migration, tube formation, and the expressions of several important neuroangiogenic factors including vascular endothelial growth factor (VEGF), brain derived neurotrophic factor (BDNF), matrix metalloproteinase (MMP) -9 and phos-JNK were measured. Low level of H2O2 significantly promoted endothelial cell (EC) proliferation, migration and tube formation and upregulated levels of VEGF, BDNF, MMP-9 and phos-JNK. DMTU and apocynin significantly inhibited endothelial angiogenesis and downregulated these protein levels. As expected, knockdown of Nox2 or Nox4 expression blocked endothelial angiogenesis and downregulated the expressions of pro-neuroangiogenic factors. Furthermore, H2O2-induced endothelial angiogenesis and high expressions of pro-neuroangiogenic factors were decreased by SP600125. In conclusion, Nox-derived ROS were required for endothelial angiogenesis. Low level of ROS may activate JNK signaling pathway and upregulate pro-neuroangiogenic factors, ultimately mediating endothelial angiogenesis.

Correction to: Parental Phubbing and Adolescents' Depressive Symptoms: Self-Esteem and Perceived Social Support as Moderators.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Parental Phubbing and Adolescents' Depressive Symptoms: Self-Esteem and Perceived Social Support as Moderators.

Parental phubbing refers to the extent to which parents use or are distracted by their cell phone when they interact with their children. There has been growing scholarly interest in understanding the adverse effects of parental phubbing on adolescents' development. However, it is less clear whether parental phubbing potentially increases adolescents' depressive symptoms, to date, and the understanding of the factors which may affect this relationship is also limited. The current study, therefore, examined the relationship between parental phubbing and adolescents' depressive symptoms and sought to determine whether self-esteem and perceived social support simultaneously moderated this relationship. The participants included 2407 students (1202 girls; Mage = 12.75, SD = 0.58) from seven middle schools in China. They completed the questionnaires regarding their experience with parental phubbing, self-esteem, perceived social support, and depressive symptoms. Results indicated that adolescents with a high level of parental phubbing were likely to have a high level of depressive symptoms, after controlling age, gender, and perceived economic stress. Low self-esteem adolescents who experienced higher levels of parental phubbing were more likely to be depressed than high self-esteem adolescents. Furthermore, higher levels of parental phubbing significantly predicted increases in adolescents' depressive symptoms when their self-esteem and perceived social support were both low, or one was low. In contrast, this effect became nonsignificant when adolescents' self-esteem and perceived social support were both high. Parents who are concerned about adolescents' depressive symptoms should pay closer attention to adolescents' self-esteem, as well as their perceived social support, in order to provide appropriate interventions.

Chronic pain induces nociceptive neurogenesis in dorsal root ganglia from Sox2-positive satellite cells.

Chronic pain is one of the most prevalent chronic diseases in the world. The plastic changes of sensory neurons in dorsal root ganglia (DRG) have been extensively studied as the underlying periphery mechanism. Recent studies revealed that satellite cells, the major glial cells in DRG, also played important roles in the development/modulation of chronic pain. Whether DRG satellite glial cells generate new neurons as their counterparts in enteric nerve ganglia and carotid body do under pathological conditions remains poorly investigated. Here, we report that chronic pain induces proliferation and upregulation of progenitor markers in the sex-determining region Y-box 2 (Sox2)- and platelet-derived growth factor receptor alpha (PDGFRα)-positive satellite glial cells. BrdU incorporation assay revealed the generation of IB4- and CGRP-positive neurons, but not NF200-positive neurons in DRG ipsilateral to injury. Genetic fate tracings showed that PDGFRα-positive cells did not generate neurons, whereas Sox2-positive cells produced both IB4- and CGRP-positive neurons. Interestingly, glial fibrillary acidic protein-positive cells, a subpopulation of Sox2-positive satellites, only gave birth to IB4-positive neurons. Local persistent delivery of tetrodotoxin to the sciatic nerve trunk significantly reduced the pain-induced neurogenesis. Furthermore, patch-clamp studies demonstrated that these glia-derived new neurons could fire action potentials and respond to capsaicin. Taken together, our data demonstrated a chronic pain-induced nociceptive neurogenesis in DRG from Sox2-positive satellite cells, indicating a possible contribution of DRG neurogenesis to the pathology of chronic pain.

The role of reactive oxygen species in angiogenesis and preventing tissue injury after brain ischemia.

Oxidative stress, which is defined as an imbalance between proxidant and antioxidant systems, is the essential mechanism involving in the ischemic process. During the early stage of brain ischemia, reactive oxygen species (ROS) are increased. Increased ROS are thought of a consequence of brain ischemia and exacerbating disease due to inducing cell death, apoptosis and senescence by oxidative stress. During brain tissue repair, ROS are act as signaling molecules and may be benefical for regulating angiogenesis and preventing tissue injury. New blood vessel formation is essentially required for rescuing tissue from brain ischemia. In ischemic conditions, ROS promotes angiogenesis, either directly or via the generation of active oxidation products. ROS-induced angiogenesis involves several signaling pathways. This paper reviewed current understanding of the role of ROS as a mediator and modulator of angiogenesis in brain ischemia.

RIPK3/MLKL-Mediated Neuronal Necroptosis Modulates the M1/M2 Polarization of Microglia/Macrophages in the Ischemic Cortex.

Cell death and subsequent inflammation are 2 key pathological changes occurring in cerebral ischemia. Active microglia/macrophages play a double-edged role depending on the balance of their M1/M2 phenotypes. Necrosis is the predominant type of cell death following ischemia. However, how necrotic cells modulate the M1/M2 polarization of microglia/macrophages remains poorly investigated. Here, we reported that ischemia induces a rapid RIPK3/MLKL-mediated neuron-dominated necroptosis, a type of programmed necrosis. Ablating RIPK3 or MLKL could switch the activation of microglia/macrophages from M1 to the M2 type in the ischemic cortex. Conditioned medium of oxygen-glucose deprivation (OGD)-treated wild-type (WT) neurons induced M1 polarization, while that of RIPK3-/- neurons favored M2 polarization. OGD treatment induces proinflammatory IL-18 and TNFα in WT but not in RIPK3-/- neurons, which in turn upregulate anti-inflammatory IL-4 and IL-10. Furthermore, the expression of Myd88-a common downstream adaptor of toll-like receptors-is significantly upregulated in the microglia/macrophages of ischemic WT but not of RIPK3-/- or MLKL-/- cortices. Antagonizing the function of Myd88 could phenocopy the effects of RIPK3/MLKL-knockout on the polarization of microglia/macrophages and was neuroprotective. Our data revealed a novel role of necroptotic neurons in modulating the M1/M2 balance of microglia/macrophages in the ischemic cortex, possibly through Myd88 signaling.

High Tg and Thermo-Oxidatively Stable Thermosetting Polyimides Derived from a Carborane-Containing Diamine.

To provide high-temperature polyimide matrix resins, novel carborane-containing thermosetting polyimides are presented. First, the low-viscosity carborane-containing imide oligomers are synthesized using newly designed 1-(3-amino-4-tolyl)-2-(4-aminophenyl)-o-carborane and aromatic dianhydride as monomers, 4-phenylethynyl phthalic anhydride as the end-capping reagent. Followed by thermal curing, the resulting polyimides show high Tg (≥500 °C) and above 92.1% char yield at 800 °C both in nitrogen and air atmosphere due to the incorporation of the bulky carborane cages. Aging studies, performed at 400 and 500 °C for 5 h in air on a carborane-containing polyimide and a carborane-free polyimide, show that the polyimide with carborane groups possesses excellent thermo-oxidative stability. Moreover, the novel polyimides exhibit constant and relatively low coefficient of thermal expansion values over a wide range of temperature, indicative of a remarkable dimensional stability. Thus, this study clearly demonstrates the viability of the incorporation of carborane cages to access polyimide thermosets with ultrahigh Tg and thermo-oxidative stability.

Effect of Combination Therapy with Neuroprotective and Vasoprotective Agents on Cerebral Ischemia.

Because most tested drugs are active against only one of the damaging processes associated with stroke, other mechanisms may cause cellular death. Thus, a combination of protective agents targeting different pathophysiological mechanisms may obtain better effects than a single agent. The major objective of this study was to investigate the effect of combination therapy with vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) after controlled ischemic brain injury in rabbits. METHODS: Animals were randomly assigned to one of the following groups: sham group, saline-treated control group or NGF+VEGF-treated group. Animals received an intracerebral microinjection of VEGF and NGF or saline at 5 or 8 hours after ischemia. The two specified time points of administration were greater than or equal to the existing therapeutic time window for monoterapy with VEGF or NGF alone (3 or 5 hours of ischemia). Infarct volume, water content, neurological deficits, neural cell apoptosis and the expression of caspase-3 and Bcl-2 were measured. RESULTS: Compared with saline-treated controls, the combination therapy of VEGF and NGF significantly reduced infarct volume, water content, neural cell apoptosis and the expression of caspase-3, up-regulated the expression of Bcl-2 and improved functional recovery (both p<0.01) when administered 5 or 8 hours after ischemia. The earlier the administration the better the neuroprotection. CONCLUSIONS: These results showed that the combination therapy with VEGF and NGF provided neuroprotective effects. In addition, the time window of combination treatment should be at least 8 hours after ischemia, which was wider than monotherapy. RÉSUMÉ: Les effets d'une polythérapie combinant agents neuro-protecteurs et agents vasoprotecteurs dans les cas d'ischémie cérébrale. Contexte:Étant donné que la plupart des médicaments préalablement testés tendent à n'agir contre seulement un des processus de dommage associés aux AVC, il est possible que d'autres processus entraînent une mort cellulaire. À cet effet, il se pourrait qu'une combinaison d'agents protecteurs ciblant divers mécanismes physiopathologiques permette d'obtenir de meilleurs résultats qu'un simple agent. Après avoir suscité de façon contrôlée des lésions cérébrales ischémiques chez des lapins, l'objectif principal de la présente étude a donc été de se pencher sur l'impact d'une polythérapie combinant la protéine dite « facteur de croissance de l'endothélium vasculaire ¼ (ou « VEGF ¼ en anglais) avec le « facteur de croissance des nerfs ¼ (ou « NGF ¼ en anglais). Méthodes: Les animaux ont été attribués au hasard à l'un des groupes suivants : ceux ayant reçu un traitement fictif ; ceux, du groupe témoin, ayant bénéficié d'un traitement à base de solution saline ; et finalement ceux ayant été traités au moyen des VEGF et NGF. À noter que les lapins ont reçu une micro-injection intracérébrale de VEGF et de NGF ou de solution saline 5 heures ou 8 heures à la suite de leur AVC. Ces deux délais d'administration des VEGF et NGF sont équivalents ou supérieurs aux délais actuels d'administration des VEGF ou NGF à titre de monothérapie (3 heures ou 5 heures à la suite d'un AVC). Tant le volume des infarctus, le contenu en eau, les déficits neurologiques ainsi causés, l'apoptose des neurones que l'expression des protéases caspase 3 et des protéines Bcl-2 ont été mesurés. Résultats: Si on la compare au traitement à base de solution saline administré au groupe témoin, la polythérapie à base de VEGF et de NGF, lorsqu'administrée 5 heures ou 8 heures à la suite de l'AVC, a su réduire de façon notable le volume des infarctus, le contenu en eau, l'apoptose des neurones et l'expression des protéases caspase 3. Elle a également permis de réguler à la hausse l'expression des protéines Bcl-2 en plus d'entraîner une amélioration de la récupération fonctionnelle (p < 0,01 pour ces deux aspects). Ainsi donc, plus tôt l'on opte pour cette polythérapie, meilleure sera la neuroprotection encourue. CONCLUSIONS: Ces résultats démontrent que la polythérapie à base de VEGF et de NGF procure des effets neuroprotecteurs. Quant au délai d'administration de ce traitement combinatoire, il devrait être d'au moins 8 heures à la suite d'un AVC, ce qui est plus élevé que la monothérapie.