Investigation of the role of sodium chloride on wheat starch multi-structure, physicochemical and digestibility properties during X-ray irradiation.

In this paper, different NaCl content was added to wheat starch and then subjected to X-ray irradiation to investigate the effect of salt on starch modification by irradiation. The results showed that the degradation of wheat starch intensified with the increase in irradiation dose. When irradiated at the same dose, wheat starch with sodium chloride produced shorter chains, lower molecular weight and amylose content, and higher crystallinity, solubility, and resistant starch than wheat starch without sodium chloride. The energy generated by X-rays dissociating sodium chloride caused damage to the glycoside bonds of the starch molecule. With a further increase in the mass fraction of NaCl, the hydrogen bonds of the starch molecules were broken, and the double helix structure was depolymerized, which exacerbated the extent of irradiation-modified wheat starch. At the same time, starch molecules will be rearranged to form a more stable structure.

Investigating the relationship between intracranial atherosclerotic plaque remodelling and diabetes using high-resolution vessel wall imaging.

BACKGROUND: Intracranial atherosclerosis, a leading cause of stroke, involves arterial plaque formation. This study explores the link between plaque remodelling patterns and diabetes using high-resolution vessel wall imaging (HR-VWI). AIM: To investigate the factors of intracranial atherosclerotic remodelling patterns and the relationship between intracranial atherosclerotic remodelling and diabetes mellitus using HR-VWI. METHODS: Ninety-four patients diagnosed with middle cerebral artery or basilar artery atherosclerosis were enrolled. Their basic clinical data were collected, and HR-VWI was performed. The vascular area at the plaque (VAMLN) and normal reference vessel (VAreference) were delineated and measured using image postprocessing software, and the Remodelling index (RI) was calculated. According to the value of the RI, the patients were divided into a positive remodelling (PR) group, intermediate remodelling (IR) group, negative remodelling (NR) group, PR group and non-PR (N-PR) group. RESULTS: The PR group exhibited a higher prevalence of diabetes and serum cholesterol levels than the IR and NR groups [45.2%, 4.54 (4.16, 5.93) vs 25%, 4.80 ± 1.22 and 16.4%, 4.14 (3.53, 4.75), respectively, P < 0.05]. The diabetes incidence was also significantly greater in the PR group than in the N-PR group (45.2% vs 17.5%, P < 0.05). Furthermore, the PR group displayed elevated serum triglyceride and cholesterol levels compared to the N-PR group [1.64 (1.23, 2.33) and 4.54 (4.16, 5.93) vs 4.54 (4.16, 5.93) and 4.24 (3.53, 4.89), P < 0.05]. Logistic regression analysis revealed diabetes mellitus as an independent influencing factor in plaque-PR [odds ratio (95% confidence interval): 3.718 (1.207-11.454), P < 0.05]. CONCLUSION: HR-VWI can clearly show the morphology and signal characteristics of intracranial vascular walls and plaques. Intracranial atherosclerotic plaques in diabetic patients are more likely to show PR, suggesting poor plaque stability and a greater risk of stroke.

Identification of sex pheromone of red swamp crayfish Procambarus clarkii and exploration of the chemosensory mechanism of their antennae.

Red swamp crayfish, Procambarus clarkii, is a globally invasive species, which has caused great damage to biodiversity, agriculture, and fishing. Therefore, the development of effective management methods, such as pheromone control, is necessary for biological control and biodiversity protection. However, the components of P. clarkii sex pheromones have not yet been explored, and the chemosensory mechanism of the P. clarkii antennae after stimulation by sex pheromone also remains unknown. In this study, we isolated and identified the candidate bioactive component of the female P. clarkii sex pheromone using ultrafiltration centrifugation, semi-preparative liquid phase separation and omics technologies and conducted bioassays to determine its attraction ability. Meanwhile, RNA-Seq technology was used to analyze the potential chemosensory mechanism of antennae. Our results indicated that the male P. clarkii were uniaxially attracted to the female crude conditioned water (FCW), medium fraction (MF, isolated by ultrafiltration centrifugation), and preparative fragment 6 of females (PFF6, isolated by semi-preparative liquid phase separation). Metabolomic analysis revealed the presence of 18 differential metabolites between the PFF6 and PFM6 samples, among which 15 were significantly upregulated in the PFF6 sample. Bioassay test also showed that mestranol, especially at concentrations of 10-5-10-2 mol∙l-1, could significantly attract P. clarkii males; therefore, mestranol was identified as the candidate sex pheromone component of P. clarkii females. Furthermore, RNA-Seq results showed that most differentially expressed genes (DEGs) enriched in lipid metabolism and signal transduction pathways were up-regulated in P. clarkii males. In addition, high expressions of Ca2+-binding protein and ion transporting ATPases may enhance the sensitivity of the antennae of P. clarkii males towards sex pheromones. Our study provides data on P. clarkii sex pheromone composition and reveals the molecular mechanism of sex pheromone response in P. clarkii. Moreover, our study provides a referable method for the isolation of candidate bioactive molecules from the P. clarkii sex pheromone.

Benefit of Using Both Ultrasound Imaging and Clinical Information for Predicting Malignant Soft Tissue Tumors.

OBJECTIVE: Ultrasonography (US) is the primary imaging method for soft tissue tumors (STTs), the diagnostic performance of which still requires improvement. To achieve an accurate evaluation of STTs, we built the diagnostic nomogram for STTs using the clinical and US features of patients with STTs. METHODS: A total of 613 patients with 195 malignant and 418 benign STTs were retrospectively recruited. We used a blend of clinical and ultrasonic features, as well as exclusively US features, to develop two distinct diagnostic models for STTs: the clinical-US model and the US-only model, respectively. The two models were evaluated and compared by measuring their areas under the receiver operating characteristic curve (AUC), calibration, integrated discrimination improvement (IDI) and decision curve analysis. The performance of the clinical-US model was also compared with that of two radiologists. RESULTS: The clinical-US model had better diagnostic performance than the model based on US imaging features alone (AUCs of the clinical-US and US-only models: 0.95 [0.93-0.97] vs. 0.89 [0.87-0.92], p < 0.001; IDI of the two models: 0.15 ± 0.03, p < 0.001). The clinical-US model was also superior to the two radiologists in diagnosing STTs (AUCs of clinical-US model and two radiologists: 0.95 [0.93-0.97] vs. 0.79 [0.75-0.82] and 0.83 [0.80-0.85], p < 0.001). CONCLUSION: The diagnostic model based on clinical and US imaging features had high diagnostic performance in STTs, which could help identify malignant STTs for radiologists.

Ultrasound features and differential diagnosis for superficial nodular fasciitis.

BACKGROUND: Nodular fasciitis (NF) has nonspecific clinical manifestations and is often misdiagnosed as sarcoma. The investigations of imaging methods for NF were limited. OBJECTIVE: To analyze the ultrasound (US) features of NF, and to evaluate the diagnostic value of US for NF. MATERIALS AND METHODS: A total of 61 NF patients were recruited retrospectively, and 551 lesions in the subcutaneous fat layer were included for comparison. We evaluated the ultrasound features of the patients and divided the NF cases into three types. Chi-square test or Fisher exact test were conducted to detect the potential difference in the distributions of three types in the two groups. RESULTS: Among the 61 NF cases, 65.6% were in the upper extremities (n = 40). The proportion of type 1, 2, and 3 were 57.4%, 24.6%, and 18.0%, respectively. NF were significantly more likely locating in the upper extremities than the other soft tissue tumors (p < 0.001). Type 1 and type 2 of sonographic features were significantly more commonly observed in NF than other soft tissue tumors among the three types (p < 0.001). CONCLUSION: The type 1 and type 2 of US features can help to distinguish NF from other lesions. US has great potential to improve the diagnostic accuracy and reduce the unnecessary surgery.

Ultrasound Assessment of Entheseal Sites and Anterior Chest Wall in Ankylosing Spondylitis: A Cross-Sectional Study.

OBJECTIVES: The study was designed to evaluate entheseal sites and anterior chest wall (ACW) of patients with ankylosing spondylitis (AS) using ultrasound (US) and investigate the correlation between disease activity and US score. METHODS: This prospective cross-sectional study included 104 patients with AS and 50 control subjects. Each patient underwent US scanning of 23 entheses and 11 sites of the ACW. The US features, including hypoechogenicity, thickness, erosion, calcification, bursitis, and Doppler signal, were evaluated. Disease activity was assessed based on C reactive protein (CRP), erythrocyte sedimentation rate (ESR), disease activity score-C reactive protein (ASDAS-CRP), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). RESULTS: The most commonly involved entheses on US were the Achilles tendon (AT) and quadriceps tendon (QT). The most involved site of ACW was the sternoclavicular joint (SCJ). Compared with the control group, significant differences were observed in the AS group in the rates of US enthesitis and ACW in AT (P = .01), SCJ (P = .00), and costochondral joint (CCJ) (P = .01). Patients with high or very high disease activity had a higher erosion score (P = .02). The erosion score was weakly positively associated with CRP, ESR, BASDAI, ASDAS-CRP, and ASDAS-ESR (correlation coefficient: 0.22-0.45). CONCLUSIONS: The most commonly involved entheseal sites on US were AT and QT, while the site of ACW was SCJ. The US assessment of AS should take the ACW into account. High disease activity might indicate erosion in AS.

The extraction and identification of active components of the sex pheromones of Asian citrus psyllid, Diaphorina citri.

In this study, we extracted and identified the active components of the Asian citrus psyllid, Diaphorina citri sex pheromones to provide a basis for further development of sex attractants. Under laboratory conditions, mating activity in D. citri started 3 d after emergence, which peaked at 6-7 d, and mating activity had no obvious peak during the observed period 7:00-21:00 h. Additionally, D. citri males were attracted to the emanations from conspecific females, especially to the n-hexane extracts of the pheromone. A total of 17 compounds were identified from the n-hexane extracts of female and male D. citri by gas chromatography-mass spectrometer (GC-MS). Among them, 13 compounds were identified from the female D. citri n-hexane extracts, of which 7 (dichloromethane, acetic acid, toluene, butyl acetate, ethyl carbamoylacetate, α-pinene, and 1-nonanal) were not found in the male D. citri n-hexane extracts. In addition, a total of 33 compounds were identified from the solid phase microextraction (SPME) volatiles of the male and female D. citri adults. Among these, 17 compounds were identified from the female D. citri volatiles, of which 6 (cycloheptatriene, 5-methyl-2-phenylindole, 1-dodecanol, cis-11-hexadecena, dodecyl aldehyde, and nerylacetone) were not identified in the volatiles of the D. citri males. It was found that males were significantly attracted to 0.1-10 µL/mL acetic acid and 1-nonanal with the selection rates ranging from 62.04%-70.56% and 62.22%-67.22%, respectively. Therefore, the results of this study suggest that acetic acid and 1-nonanal might be the active compounds of the female D. citri sex pheromones.

Comparative mitogenome analysis and phylogenetic inference of the genus Ultragryllacris (Orthoptera: Gryllacrididae).

The genus Ultragryllacris is mainly distributed in China and Thailand, and the type species Ultragryllacris pulchra Gorochov & Dawwrueng, 2015 includes four subspecies. Up to now, these subspecies were identified mainly based on their morphological characteristics, and no study on the molecular identification of subspecies and phylogenetic analyses has been reported. Here we obtained three mitogenomes of U. pulchra rubricapitis and one mitogenome of Homogryllacris yunnana and reconstructed the relationship of Ultragryllacris among genera. Species identification was performed with ABGD, jMOTU, and NJ tree based on cox1 (658 bp) and cob (550 bp) genes. The mitogenomes of U. pulchra rubricapitis and H. yunnana were 15558-16625 bp and 16209 bp in length, respectively. Most of the PCGs started with the typical ATN codons and terminated with complete TAA/TAG. Four mitogenomes showed positive AT skews and negative GC skews. Besides, the phylogenetic tree of BI and ML revealed that Ultragryllacris was a monophyletic group. One geographical population of Ultragryllacris pulchra rubricapitis was described and illustrated.

In vitro antifungal activity of lasiodiplodin, isolated from endophytic fungus Lasiodiplodia pseudotheobromae J-10 associated with Sarcandra glabra and optimization of culture conditions for lasiodiplodin production.

A macrolide antibiotic, lasiodiplodin was isolated from the endophytic fungus (EF) Lasiodiplodia pseudotheobromae J-10 associated with the medicinal plant Sarcandra glabra. In vitro antifungal assay demonstrated the inhibitory activity of lasiodiplodin against the growth of six phytopathogenic fungi, with the IC50 values ranging between 15.50 and 52.30 µg/mL. The highest antifungal activities were recorded against Exserohilum turcicum, Colletotrichum capsici, and Pestalotiopsis theae, with IC50 values of 15.50, 15.90, and 17.55 µg/mL, respectively. The underlying mechanism of the antifungal activity of lasiodiplodin against E. turcicum included the alteration of its colony morphology and disturbance of its cell membrane integrity. In addition, the optimization of L. pseudotheobromae J-10 culture conditions increased lasiodiplodin yield to 52.33 mg/L from 0.59 mg/L at pre-optimization. This is the first report on the isolation and identification of antifungal compound from the EF L. pseudotheobromae J-10 associated with S. glabra, as well as on the optimization of L. pseudotheobromae J-10 culture conditions to increase lasiodiplodin yield. The results of this study support that lasiodiplodin is a natural compound with high potential bioactivity against phytopathogens, and provide a basis for further study of the EF associated with S. glabra.

The NEDD8-activating enzyme inhibitor MLN4924 reduces ischemic brain injury in mice.

Blood-brain barrier (BBB) breakdown and inflammation occurring at the BBB have a key, mainly a deleterious role in the pathophysiology of ischemic stroke. Neddylation is a ubiquitylation-like pathway that is critical in various cellular functions by conjugating neuronal precursor cell-expressed developmentally down-regulated protein 8 (NEDD8) to target proteins. However, the roles of neddylation pathway in ischemic stroke remain elusive. Here, we report that NEDD8 conjugation increased during acute phase after ischemic stroke and was present in intravascular and intraparenchymal neutrophils. Inhibition of neddylation by MLN4924, also known as pevonedistat, inactivated cullin-RING E3 ligase (CRL), and reduced brain infarction and improved functional outcomes. MLN4924 treatment induced the accumulation of the CRL substrate neurofibromatosis 1 (NF1). By using virus-mediated NF1 silencing, we show that NF1 knockdown abolished MLN4924-dependent inhibition of neutrophil trafficking. These effects were mediated through activation of endothelial P-selectin and intercellular adhesion molecule-1 (ICAM-1), and blocking antibodies against P-selectin or anti-ICAM-1 antibodies reversed NF1 silencing-induced increase in neutrophil infiltration in MLN4924-treated mice. Furthermore, we found that NF1 silencing blocked MLN4924-afforded BBB protection and neuroprotection through activation of protein kinase C δ (PKCδ), myristoylated alanine-rich C-kinase substrate (MARCKS), and myosin light chain (MLC) in cerebral microvessels after ischemic stroke, and treatment of mice with the PKCδ inhibitor rottlerin reduced this increased BBB permeability. Our study demonstrated that increased neddylation promoted neutrophil trafficking and thus exacerbated injury of the BBB and stroke outcomes. We suggest that the neddylation inhibition may be beneficial in ischemic stroke.

Hippocampal alpha-synuclein mediates depressive-like behaviors.

Alpha-synuclein (α-syn) which encoded by SNCA plays a critical role in the neurotransmission, vesicle dynamics, and neuroplasticity. Alteration to SNCA expression is associated with major depressive disorder. However, the pathogenic mechanism of SNCA in depression remains unknown. Herein, we reported that SNCA was up-regulated in the peripheral blood of major depressive disorder (MDD) patients and the depressive mice. Chronic restraint stress (CRS) also up-regulated the SNCA expression in the hippocampus. Moreover, over-expression of SNCA in the hippocampus triggered spontaneous depressive-like behaviors under the non-stressed conditions in mice, and knockout of SNCA could reverse CRS-induced depressive-like behaviors. SNCA led to synapse loss and neuronal cell death in the hippocampus possibly via complement-mediated microglial engulfment and inflammation, and thus contributed to the pathogenesis of depressive disorder. Overall, hippocampal SNCA and complement system are involved in the pathogenesis of depressive disorder and it provides a new perspective for the occurrence of depressive disorder.

New additions to the Chinese Agraeciini Redtenbacher, 1891 (Orthoptera, Tettigoniidae: Conocephalinae) with report the complete mitochondrial genome of Palaeoagraecia brunnea Ingrisch, 1998.

This paper reports one newly recorded species and one new species from China, namely Anelytra (Lichnofugia) symfioma (Ingrisch, 1998) and Liara (Liara) shii Liu Bian sp. nov. All the species of Agraeciini Redtenbacher, 1891 from China are listed. The examined specimens are deposited in Guangxi Normal University. The complete mitochondrial genome of Palaeoagraecia brunnea Ingrisch, 1998 was 15984 bp and consisted of 37 genes and a control region. The A + T content of the mitogenome was as high as 70.2%. Most protein-coding genes started with the codon ATN and ended with typical stop codons TAA. Phylogenetic analyses based on mitogenomes suggested that Palaeoagraecia brunnea and the genus Pseudorhynchus had the closest genetic relationship.

Preoperative Axillary Ultrasound Helps in the Identification of a Limited Nodal Burden in Breast Cancer Patients.

Since the Z0011 trial, the clinical evaluation of axillary status has been redirected to predicting nodal tumor burden rather than nodal metastases. Our study aimed to evaluate the value of clinicopathological factors and axillary ultrasound (US) for the prediction of a high nodal burden (≥3 metastatic lymph nodes) in breast cancer patients. A total of 532 consecutive patients who underwent preoperative axillary US and subsequent surgery for clinical T1-2 breast cancer with a final pathologic analysis were included. Clinical and pathologic variables were retrospectively evaluated. Univariate and multivariate statistical analyses were performed to identify the variables that were associated with a high nodal burden. Among the 532 patients, 110 (20.7%) had a high axillary nodal burden and 422 (79.3%) had a limited nodal burden. The multivariate analysis showed that suspicious axillary US findings (P < 0.001), clinical T2 stage (P = 0.011), the presence of lymphovascular invasion (P < 0.001), and estrogen receptor positivity (P < 0.001) were significantly associated with a high nodal burden. Patients with negative axillary US findings seldom had a high nodal burden, with a negative predictive value of 93.0% (294/316). Patients with suspicious axillary US findings, clinical T2 stage, lymphovascular invasion, and estrogen receptor positivity are more likely to have a high nodal burden, which may provide additional information for the treatment plan of breast cancer patients. Preoperative axillary US helps identify a limited nodal burden in breast cancer patients and has implications for axillary lymph node dissection and adjuvant treatment.

Neutrophil extracellular traps released by neutrophils impair revascularization and vascular remodeling after stroke.

Neovascularization and vascular remodeling are functionally important for brain repair after stroke. We show that neutrophils accumulate in the peri-infarct cortex during all stages of ischemic stroke. Neutrophils producing intravascular and intraparenchymal neutrophil extracellular traps (NETs) peak at 3-5 days. Neutrophil depletion reduces blood-brain barrier (BBB) breakdown and enhances neovascularization at 14 days. Peptidylarginine deiminase 4 (PAD4), an enzyme essential for NET formation, is upregulated in peri-ischemic brains. Overexpression of PAD4 induces an increase in NET formation that is accompanied by reduced neovascularization and increased BBB damage. Disruption of NETs by DNase 1 and inhibition of NET formation by genetic ablation or pharmacologic inhibition of PAD increases neovascularization and vascular repair and improves functional recovery. Furthermore, PAD inhibition reduces stroke-induced STING-mediated production of IFN-ß, and STING knockdown and IFN receptor-neutralizing antibody treatment reduces BBB breakdown and increases vascular plasticity. Collectively, our results indicate that NET release impairs vascular remodeling during stroke recovery.

Injection of α-syn-98 Aggregates Into the Brain Triggers α-Synuclein Pathology and an Inflammatory Response.

Pathological aggregation of α-synuclein (α-syn) is a major component of Lewy bodies (LB), which play a central role in pathogenesis of Parkinson's disease (PD). Differential expression of α-syn isoforms has been shown in PD. Isoform α-syn-98 is generated by excision of exon-3 and exon-5 of the α-syn gene. In contrast to the canonical full-length α-syn isoform (α-syn140), little is known about the function of the α-syn-98 isoform. In the present study, to identify the potential role of α-syn-98 protein in PD, we examined the effects of exogenous recombinant insoluble α-syn-98 aggregates on α-syn pathology and inflammatory responses in the midbrain. After injection of α-syn-98 aggregates into the substantia nigra (SN), mice exhibited motor dysfunction accompanied by nigral dopaminergic neuron loss. In addition, α-syn-98 aggregates injection resulted in a significant increase in phosphorylation of endogenous α-syn. Accumulations of α-syn were co-localized with p62 and ubiquitin, which suggests α-syn-98 aggregates-induced pathology exhibits properties similar to human LB. Many glial cells were activated after α-syn-98 aggregates injection. In addition, expression of NF-κB, interleukin 6 (IL6), and tumor necrosis factor-α (TNF-α) and levels of oxidative stress increased after α-syn-98 aggregates injection. Our results suggest that α-syn-98 may play a crucial role in the pathogenesis of PD.

ADAMTS13 maintains cerebrovascular integrity to ameliorate Alzheimer-like pathology.

Blood-brain barrier (BBB) defects and cerebrovascular dysfunction contribute to amyloid-ß (Aß) brain accumulation and drive Alzheimer disease (AD) pathology. By regulating vascular functions and inflammation in the microvasculature, a disintegrin and metalloprotease with thrombospondin type I motif, member 13 (ADAMTS13) plays a significant protective effect in atherosclerosis and stroke. However, whether ADAMTS13 influences AD pathogenesis remains unclear. Using in vivo multiphoton microscopy, histological, behavioral, and biological methods, we determined BBB integrity, cerebrovascular dysfunction, amyloid accumulation, and cognitive impairment in APPPS1 mice lacking ADAMTS13. We also tested the impact of viral-mediated expression of ADAMTS13 on cerebrovascular function and AD-like pathology in APPPS1 mice. We show that ADAMTS13 deficiency led to an early and progressive BBB breakdown as well as reductions in vessel density, capillary perfusion, and cerebral blood flow in APPPS1 mice. We found that deficiency of ADAMTS13 increased brain plaque load and Aß levels and accelerated cerebral amyloid angiopathy (CAA) by impeding BBB-mediated clearance of brain Aß, resulting in worse cognitive decline in APPPS1 mice. Virus-mediated expression of ADAMTS13 attenuated BBB disruption and increased microvessels, capillary perfusion, and cerebral blood flow in APPPS1 mice already showing BBB damage and plaque deposition. These beneficial vascular effects were reflected by increase in clearance of cerebral Aß, reductions in Aß brain accumulation, and improvements in cognitive performance. Our results show that ADAMTS13 deficiency contributes to AD cerebrovascular dysfunction and the resulting pathogenesis and cognitive deficits and suggest that ADAMTS13 may offer novel therapeutic opportunities for AD.

Transfusion of Resting Platelets Reduces Brain Hemorrhage After Intracerebral Hemorrhage and tPA-Induced Hemorrhage After Cerebral Ischemia.

BACKGROUND: Exacerbated blood-brain barrier (BBB) damage is related with tissue plasminogen activator (tPA)-induced brain hemorrhage after stroke. Platelets have long been recognized as the cellular orchestrators of primary haemostasis. Recent studies have demonstrated further that platelets are required for supporting intact mature blood vessels and play a crucial role in maintaining vascular integrity during inflammation. Therefore, we sought to investigate whether platelets could reduce tPA-induced deterioration of cerebrovascular integrity and lead to less hemorrhagic transformation. METHODS: Mice were subjected to models of collagenase-induced intracerebral hemorrhage (ICH) and transient middle cerebral artery (MCA) occlusion. After 2 h of MCA occlusion, tPA (10 mg/kg) was administered as an intravenous bolus injection of 1 mg/kg followed by a 9 mg/kg infusion for 30 min. Immediately after tPA treatment, mice were transfused with platelets. Hemorrhagic volume, infarct size, neurological deficit, tight junction and basal membrane damages, endothelial cell apoptosis, and extravascular accumulation of circulating dextran and IgG, and Evans blue were quantified at 24 h. RESULTS: Platelet transfusion resulted in a significant decrease in hematoma volume after ICH. In mice after ischemia, tPA administration increased brain hemorrhage transformation and this was reversed by resting but not activated platelets. Consistent with this, we observed that tPA-induced brain hemorrhage was dramatically exacerbated in thrombocytopenic mice. Transfusion of resting platelets ameliorated tPA-induced loss of cerebrovascular integrity and reduced extravascular accumulation of circulating serum proteins and Evans blue, associated with improved neurological functions after ischemia. No changes were found for infarct volume. Inhibition of platelet receptor glycoprotein VI (GPVI) blunted the ability of platelets to attenuate tPA-induced BBB disruption and hemorrhage after ischemia. CONCLUSION: Our findings demonstrate the importance of platelets in safeguarding BBB integrity and suggest that transfusion of resting platelets may be useful to improve the safety of tPA thrombolysis in ischemic stroke.

Growth Differentiation Factor 11 Promotes Neurovascular Recovery After Stroke in Mice.

Background: Growth differentiation factor 11 (GDF11), a member of transforming growth factor-ß (TGF-ß) superfamily, was shown to rejuvenate cardiac and skeletal muscle function and to improve cerebral vasculature and neurogenesis in old mice. However, recent experimental data reported that raising GDF11 levels inhibited skeletal muscle regeneration and had no effect on cardiac hypertrophy. Our aim was to investigate the effects of GDF11 on brain repair during the recovery phase after stroke. Methods: Mice were subjected to distal middle cerebral artery occlusion, and recombinant GDF11 (rGDF11) was injected intraperitoneally once a day during days 7-13 after stroke. Neuronal precursor cells (NPCs) proliferation and angiogenesis were assayed at 14 days. Neuronal regeneration was assayed at 42 days. The beam-walking test and CatWalk were used to evaluate behavioral functions. Downstream pathways of GDF11 were also investigated. Results: GDF11 was upregulated in the ipsilateral peri-infarct cortex and subventricular zone (SVZ) at 14 days after stroke. Treatment with rGDF11 enhanced the number of newborn NPCs and endothelial cells, microvascular length and area, and brain capillary perfusion. Western blots showed that rGDF11 upregulated brain-derived neurotrophic factor (BDNF) and increased the levels of proangiogenic factor angiopoietin-2 (Ang-2) and phosphorylation of vascular endothelial growth factor receptor-2 (VEGFR-2). We also found that rGDF11 upregulated the transcription factors Smad2 and Smad3 phosphorylation, but these activations were blocked by a TGF-ß receptor inhibitor SB431542. Moreover, rGDF11-induced angiogenic remodeling and NPCs proliferation were reversed by injection of SB431542, suggesting that GDF11 may exert its effect via the TGF-ß/Smad2/3 signaling pathway. Finally, treating mice with rGDF11 resulted in a significant increase in neuronal regeneration and functional recovery. Conclusion: GDF11 promoted neurogenesis and angiogenesis and contributed to functional recovery after stroke in mice.