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1.
Acta Neuropathol ; 147(1): 79, 2024 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-38705966

RESUMO

Although human females appear be at a higher risk of concussion and suffer worse outcomes than males, underlying mechanisms remain unclear. With increasing recognition that damage to white matter axons is a key pathologic substrate of concussion, we used a clinically relevant swine model of concussion to explore potential sex differences in the extent of axonal pathologies. At 24 h post-injury, female swine displayed a greater number of swollen axonal profiles and more widespread loss of axonal sodium channels than males. Axon degeneration for both sexes appeared to be related to individual axon architecture, reflected by a selective loss of small caliber axons after concussion. However, female brains had a higher percentage of small caliber axons, leading to more extensive axon loss after injury compared to males. Accordingly, sexual dimorphism in axonal size is associated with more extensive axonal pathology in females after concussion, which may contribute to worse outcomes.


Assuntos
Axônios , Concussão Encefálica , Modelos Animais de Doenças , Caracteres Sexuais , Animais , Feminino , Axônios/patologia , Concussão Encefálica/patologia , Masculino , Suínos , Encéfalo/patologia
2.
J Periodontal Res ; 58(6): 1235-1247, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37712743

RESUMO

BACKGROUND: Periodontal ligament stem cells (PDLSCs) are the most potential cells in periodontal tissue regeneration and bone tissue regeneration. Our prior work had revealed that WD repeat-containing protein 72 (WDR72) was crucial for osteogenic differentiation of PDLSCs. Here, we further elucidated its underlying mechanism in PDLSC osteogenic differentiation. METHODS: Human PDLSCs, isolated and identified by flow cytometry, were prepared for osteogenic differentiation induction. Levels of WDR72, long non-coding RNA X-Inactive Specific Transcript (XIST), upstream stimulatory factor 2 (USF2), and osteogenic marker genes (Runx2, Osteocalcin, and Collagen I) in human PDLSCs and clinical specimens were detected by RT-qPCR. Protein expressions of WDR72, Runx2, Osteocalcin, and Colla1 were tested by Western blot. The interactions among the molecules were verified by RIP, RNA pull-down, ChIP, and luciferase reporter assays. Osteogenic differentiation was evaluated by alkaline phosphatase (ALP) and alizarin red staining (ARS). RESULTS: WDR72 was decreased in periodontal tissues of periodontitis patients, and overexpression reversed TNF-α-mediated suppressive effects on PDLSC osteogenic differentiation. Mechanically, XIST recruited the enrichment of USF2 to the WDR72 promoter region, thereby positively regulating WDR72. WDR72 silencing overturned XIST-mediated biological effects in PDLSCs. CONCLUSION: WDR72, regulated by the XIST/USF2 axis, enhances osteogenic differentiation of PDLSCs, implying a novel strategy for alleviating periodontitis.


Assuntos
Periodontite , RNA Longo não Codificante , Humanos , Diferenciação Celular , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Osteocalcina/metabolismo , Osteogênese , Ligamento Periodontal , Periodontite/metabolismo , Proteínas/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Células-Tronco/metabolismo , Fatores Estimuladores Upstream/metabolismo
3.
Heart Surg Forum ; 26(4): E336-E345, 2023 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-37691275

RESUMO

BACKGROUND: High rates of mortality and aortic arch stenosis have been reported for one-stage radical surgery of interruption of aortic arch (IAA) with ventricular septal defect (VSD) and other associated intracardiac defects, but the sample size of the study is relatively small, and the credibility of the study is not high. The risk factors of death and aortic arch stenosis will be analyzed in a large sample size of infants with IAA, VSD and other associated intracardiac defects after one-stage radical resection. METHODS: A retrospective analysis was performed on 152 children with IAA, VSD and other associated intracardiac defects from January 2006 to January 2017 who had undergone one-stage radical resection, including 95 cases of type A and 57 cases of type B. January 2006-December 2011 as the early period, and January 2012-January 2017 as the late period. Cox proportional hazards regression model was used to analyze the risk factors for mortality and aortic arch stenosis after surgery, the overall survival rate was analyzed by the Kaplan-Meier method, and the survival curve was drawn by GraphPad Prism 8 software. RESULTS: 22 cases (14.47%) died, 27 cases (17.76%) developed aortic arch stenosis. The 1-month, 3-month, 6-month, 1-year, 3-year, and 5-year survival rates were 85.53%, 85.53%, 85.53%, 84.21%, 78.95% and 75.66%, respectively. Low age (Hazard Ratio (HR) = 0.551, 95% Confidence Interval (CI): 0.320-0.984, p = 0.004), low body weight (HR = 0.632, 95% CI: 0.313-0.966, p = 0.003), large ratio of VSD diameter/aortic diameter (VSD/AO) (HR = 2.547, 95% CI: 1.095-7.517, p = 0.044), long duration of cardiopulmonary bypass (HR = 1.374, 95% CI: 1.000-3.227, p = 0.038), and left ventricular outflow tract obstruction (LVOTO) (HR = 3.959, 95% CI: 1.123-9.268, p = 0.015) were independent risk factors for postoperative death. The surgical period (January 2006-December 2011) (HR = 0.439, 95% CI: 0.109-0.964, p = 0.046) and the addition of pericardial anastomosis to the anterior aortic wall (HR = 0.398, 95% CI: 0.182-0.870, p = 0.021) were independent risk factors for postoperative aortic arch stenosis. CONCLUSIONS: Children with low age, low body weight, large ratio of VSD/AO, long duration of cardiopulmonary bypass, LVOTO, the surgical period (January 2006-December 2011) and pericardial anastomosis with anterior aortic wall have poor prognosis.


Assuntos
Coartação Aórtica , Estenose da Valva Aórtica , Comunicação Interventricular , Obstrução da Via de Saída Ventricular Esquerda , Lactente , Criança , Humanos , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Constrição Patológica , Estudos Retrospectivos , Comunicação Interventricular/complicações , Comunicação Interventricular/diagnóstico , Comunicação Interventricular/cirurgia , Pericárdio , Prognóstico , Peso Corporal
4.
Acta Neuropathol ; 144(5): 967-985, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36107227

RESUMO

Despite being a major health concern, little is known about the pathophysiological changes that underly concussion. Nonetheless, emerging evidence suggests that selective damage to white matter axons, or diffuse axonal injury (DAI), disrupts brain network connectivity and function. While voltage-gated sodium channels (NaChs) and their anchoring proteins at the nodes of Ranvier (NOR) on axons are key elements of the brain's network signaling machinery, changes in their integrity have not been studied in context with DAI. Here, we utilized a clinically relevant swine model of concussion that induces evolving axonal pathology, demonstrated by accumulation of amyloid precursor protein (APP) across the white matter. Over a two-week follow-up post-concussion with this model, we found widespread loss of NaCh isoform 1.6 (Nav1.6), progressive increases in NOR length, the appearance of void and heminodes and loss of ßIV-spectrin, ankyrin G, and neurofascin 186 or their collective diffusion into the paranode. Notably, these changes were in close proximity, yet distinct from APP-immunoreactive swollen axonal profiles, potentially representing a unique, newfound phenotype of axonal pathology in DAI. Since concussion in humans is non-fatal, the clinical relevance of these findings was determined through examination of post-mortem brain tissue from humans with higher levels of acute traumatic brain injury. Here, a similar loss of Nav1.6 and changes in NOR structures in brain white matter were observed as found in the swine model of concussion. Collectively, this widespread and progressive disruption of NaChs and NOR appears to be a form of sodium channelopathy, which may represent an important substrate underlying brain network dysfunction after concussion.


Assuntos
Concussão Encefálica , Lesões Encefálicas , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Anquirinas/análise , Anquirinas/metabolismo , Axônios/patologia , Concussão Encefálica/patologia , Lesões Encefálicas/patologia , Humanos , Isoformas de Proteínas/metabolismo , Nós Neurofibrosos/química , Nós Neurofibrosos/metabolismo , Nós Neurofibrosos/patologia , Sódio/metabolismo , Canais de Sódio/análise , Canais de Sódio/metabolismo , Espectrina/análise , Espectrina/metabolismo , Suínos
5.
J Surg Res ; 280: 196-203, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35994981

RESUMO

INTRODUCTION: Beta-blockers (BB) after traumatic brain injury (TBI) accelerate cognitive recovery weeks after injury. BBs also inhibit leukocyte (LEU) mobilization to the penumbral blood brain barrier (BBB) 48-h after TBI. It is unclear whether the latter effects persist longer and accompany the persistent cognitive improvement. We hypothesized that 2 wk of BB after TBI reduce penumbral BBB leukocyte-endothelial interactions. METHODS: Thirty CD1 mice underwent TBI (controlled cortical impact, CCI: 6 m/s velocity, 1 mm depth, 3 mm diameter) or sham craniotomy followed by i.p. saline (NS) or propranolol (1, 2, 4 mg/kg) every 12 h for 14 d. On day 14, in vivo pial intravital microscopy visualized endothelial-LEU interactions and BBB microvascular leakage. Day 14 Garcia neurological test scores and animal weights were compared to preinjury levels reflecting concurrent clinical recovery. RESULTS: LEU rolling was greatest in CCI + NS when compared to sham (P = 0.03). 4 mg/kg propranolol significantly reduced postCCI LEU rolling down to uninjured sham levels (P = 0.03). LEU adhesion and microvascular permeability were not impacted at this time interval. Untreated injured animals (CCI + NS) scored lower Garcia neurological test and greater weight loss recovery at day 14 when compared to preinjury (P < 0.05). Treatment with higher doses of propranolol (2, 4 mg/kg), improved weight loss recovery (P < 0.001). CONCLUSIONS: LEU rolling alone, was influenced by BB therapy 14 d after TBI suggesting that certain penumbral neuroinflammatory cellular effects of BB therapy after TBI persist up to 2 wk after injury potentially explaining the pervasive beneficial effects of BBs on learning and memory.


Assuntos
Edema Encefálico , Lesões Encefálicas Traumáticas , Animais , Camundongos , Barreira Hematoencefálica , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Modelos Animais de Doenças , Leucócitos , Propranolol/farmacologia , Propranolol/uso terapêutico , Redução de Peso
6.
BMC Cardiovasc Disord ; 22(1): 112, 2022 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-35300595

RESUMO

BACKGROUND: To explore the effect of initial surgery for type I and II pulmonary atresia with intact ventricular septum (PA/IVS). METHODS: 50 children with type I PA/IVS and 50 with type II PA/IVS who had undergone initial surgery were enrolled. Children with Type I were divided into groups A (n = 25) and B (n = 25). Group A had received BT shunt combined with PDA ligation and balloon dilatation of pulmonary valve, whereas group B had undergone BT shunt combined with PDA ligation and pulmonary valve incision. Children with type II were divided into groups C (n = 25) and D (n = 25). Group C had received BT shunt combined with PDA ligation, right ventricular outflow tract (RVOT) incision and transannular patch. Group D had undergone BT shunt combined with PDA ligation, RVOT incision, transannular patch and artificial pulmonary valve implantation. The differences in mechanical ventilation time, length of ICU stay, mortality rate, tricuspid Z value, tricuspid regurgitation, oxygen saturation, pulmonary regurgitation, McGoon ratio, pulmonary artery transvalvular pressure, survival rate were compared between groups A and B, between groups C and D respectively. RESULTS: The ventilator assistance time and length of ICU stay were greater in group C than in group D (80.96 ± 8.42 h vs. 65.16 ± 4.85 h, P = 0.045; 222.00 ± 11.72 h vs. 162.48 ± 7.91 h, P = 0.048). The pulmonary artery transvalvular pressure was significantly higher in group A than in group B at 3, 6, 12, 24 and 36 months after surgery (64.86 ± 4.13 mmHg vs. 53.04 ± 5.64 mmHg, P = 0.045; 69.47 ± 1.93 mmHg vs. 55.95 ± 4.04 mmHg, P = 0.005; 80.16 ± 3.76 mmHg vs. 73.24 ± 2.34 mmHg, P = 0.035; 62.95 ± 5.64 mmHg vs. 48.47 ± 7.44 mmHg, P = 0.04; 53.69 ± 4.89 vs. 45.77 ± 3.26, P = 0.02). Furthermore, the tricuspid Z value was significantly greater in group B than in group A at 3 and 24 months after surgery (- (1.37 ± 0.04) vs. - (1.43 ± 0.06), P = 0.03; - (0.41 ± 0.06) vs. - (0.51 ± 0.11), P = 0.02). CONCLUSIONS: The effect of BT shunt combined with PDA ligation and pulmonary valve incision is superior to BT shunt combined with PDA ligation and balloon dilatation of pulmonary valve, and the effect of BT shunt combined with PDA ligation, RVOT incision, transannular patch and artificial pulmonary valve implantation is superior to BT shunt combined with PDA ligation, RVOT incision and transannular patch.


Assuntos
Cardiopatias Congênitas , Atresia Pulmonar , Insuficiência da Valva Pulmonar , Valva Pulmonar , Criança , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Atresia Pulmonar/diagnóstico por imagem , Atresia Pulmonar/cirurgia , Valva Pulmonar/diagnóstico por imagem , Valva Pulmonar/cirurgia , Resultado do Tratamento
8.
Zhongguo Zhong Yao Za Zhi ; 45(24): 5951-5957, 2020 Dec.
Artigo em Zh | MEDLINE | ID: mdl-33496134

RESUMO

Based on the results of the fourth national survey of traditional Chinese medicine resources in Turpan city, Xinjiang, this study counted the types of traditional Chinese medicine resources in Turpan Basin. The spatial distribution differences of traditional Chinese medicine resources in Turpan Basin of Xinjiang were analyzed by using grid technology, trend surface analysis, global spatial autocorrelation analysis, and local spatial autocorrelation analysis, so as to clarify the overall change trend and aggregation degree of traditional Chinese medicine resources in Turpan Basin in horizontal and vertical directions. The results showed the following: in the horizontal direction, the species richness of traditional Chinese medicine resources in the central part of Turpan Basin was high, and there were great differences in the species richness of traditional Chinese medicine resources in Turpan Basin under different grid sizes. The spatial scale effect of the richness of traditional Chinese medicine resources in Turpan Basin is obvious. Among them, under the 30 km×30 km scale, the richness of the types of Chinese medicine resources shows a high spatial correlation, and the richness of the types of Chinese medicine resources at 5 km×5 km scale presents a near random distribution state, and the richness of the types of Chinese medicine resources at 80, 90, and 100 km scale sits negatively related. Vertical direction, Chinese medicine resources appear rich at the range of-154-150 m and 900-1 050 m following by range of 1 050-1 200 m.


Assuntos
Medicina Tradicional Chinesa , Tecnologia , China , Análise Espacial
10.
Sci Rep ; 14(1): 14495, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914729

RESUMO

Investigating surfactant effects on the floatability of Wiser bituminous coal holds significant importance in improving coal cleanliness and utilization value. Using density functional theory and molecular dynamics simulation methods, this study constructed models of Wiser bituminous coal and examined the impact of different surfactants, including the anionic surfactant sodium dodecyl benzene sulfonate, the cationic surfactant hexadecyl trimethyl ammonium bromide (CTAB), and the non-ionic surfactant fatty alcohol ethoxylated ether. The focus was on investigating the charge distribution characteristics of these molecules and the modifying effect of binary surfactants on the hydrophobicity of bituminous coal. Results revealed that the maximum electrostatic potential was concentrated near oxygen/nitrogen/sulfur-containing functional groups like sulfonic acid groups, quaternary ammonium cations, ethylene oxide, hydroxyl groups, carboxyl groups, and sulfur bonds. These functional groups exhibited a propensity for accepting/delivering electrons to form hydrogen bonds. Among the surfactants tested, CTAB revealed the slightest difference in frontier orbital energy, measuring 3.187 eV, thereby demonstrating a superior trapping ability compared with the other two surfactants. Adsorption reactions within the system were determined to be spontaneous, with over 60% of the interaction force attributed to electrostatic forces. Moreover, the repulsive force magnitude with water molecules followed the trend: sulfonate group (2.20 Å) < ethylene oxide (2.43 Å) < quaternary ammonium cation (2.57 Å), indicating more excellent water repellency of CTAB. Findings showed that CTAE binary surfactants proved most effective in modifying the hydrophobicity of bituminous coal. This study offers valuable insights into reducing waste, pollution, and resource wastage.

11.
Sci Rep ; 14(1): 4209, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378840

RESUMO

Deep clustering has been widely applicated in various fields, including natural image and language processing. However, when it is applied to hyperspectral image (HSI) processing, it encounters challenges due to high dimensionality of HSI and complex spatial-spectral characteristics. This study introduces a kind of deep clustering model specifically tailed for HSI analysis. To address the high dimensionality issue, redundant dimension of HSI is firstly eliminated by combining principal component analysis (PCA) with t-distributed stochastic neighbor embedding (t-SNE). The reduced dataset is then input into a three-dimensional attention convolutional autoencoder (3D-ACAE) to extract essential spatial-spectral features. The 3D-ACAE uses spatial-spectral attention mechanism to enhance captured features. Finally, these enhanced features pass through an embedding layer to create a compact data-representation, and the compact data-representation is divided into distinct clusters by clustering layer. Experimental results on three publicly available datasets validate the superiority of the proposed model for HSI analysis.

12.
Eur Heart J Case Rep ; 7(11): ytad527, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38025123

RESUMO

Background: Pulmonary hypertensive crisis is a complication with extremely high mortality after surgery of congenital heart disease. However, there are still no treatment guidelines or expert consensus on the standard treatment of pulmonary hypertensive crisis, and the effect of conventional treatment is still unsatisfactory. We present a case of a patient who developed pulmonary hypertensive crisis after cardiac surgery, and was successfully rescued with a pioneering method, which has never been reported so far. Case summary: An infant with congenital heart disease had undergone cardiac surgery successfully. Due to obvious myocardial oedema, sternal closure was delayed. The left atrial and right ventricular pressure monitoring tubes, both of which were connected through a triplet, were inserted into right pulmonary vein and pulmonary artery, respectively, and the triplet was in closed condition. On the night of the surgery, pulmonary hypertensive crisis occurred. Emergency bedside thoracotomy was given, and the triplet was turned on urgently to make the left atrial and right ventricular pressure monitoring tubes connected. Meantime, conventional treatment was performed. Eventually, the pulmonary hypertensive crisis was quickly relieved, and the infant was discharged 9 days later. Discussion: The left atrial and right ventricular pressure monitoring tubes are placed intraoperatively in patients who both need delayed sternal closure and have high risk factors for pulmonary hypertensive crisis, by which could not only monitor the pressure of left atrium and right ventricle in real time but also effectively relieve the right ventricular pressure instantaneously when pulmonary hypertensive crisis occurs, as well as remedy ischaemia of systemic and coronary circulation.

13.
ACS Omega ; 8(3): 3461-3469, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36713738

RESUMO

Obvious differences exist in the structures of different coal rank coals, resulting in many differences and similarities in the amount of methane (CH4) gas adsorbed by coal and the control mechanism. In this study, we conducted adsorption simulations of three different coal rank coals in the superposition state using the Materials Studio software with simulated temperatures of 293.15, 313.15, and 333.15 K and adsorption pressures ranging from 0 to 10 MPa. We used the grand canonical ensemble Monte Carlo calculation method to calculate and study the adsorption amount, adsorption process, isosteric heat, and diffusion coefficient of CH4 in detail. We found that the adsorption of CH4 by coal samples of three coal rank coals (i.e., anthracite, bituminous coal, and lignite), which were mixed and stacked separately, was concentrated in the effective pores of coal molecules. Their effect on the amount of CH4 adsorption was dominated by the coal samples with more effective pores in the coal molecules. The isosteric heat of the coal samples showed an obvious exponential relationship with the adsorption pressure, and the isosteric heat of coal samples as a nonhomogeneous adsorbent gradually decreased with an increase in adsorption pressure. During the transformation of free-state CH4 into an adsorbed state, we obtained the best adsorption effect for bituminous-lignite superposition-state coal samples, and the diffusion coefficient of CH4 was the lowest.

14.
J Trauma Acute Care Surg ; 95(1): 47-54, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37038259

RESUMO

BACKGROUND: Tranexamic acid (TXA) given early, but not late, after traumatic brain injury (TBI) appears to improve survival. This may be partly related to TXA-driven profibrinolysis and increased leukocyte (LEU)-mediated inflammation when administered late post-injury. We hypothesized that early TXA (1 hour post-TBI), blunts penumbral, blood-brain barrier (BBB) leukocyte-endothelial cell (LEU-EC) interactions and microvascular permeability, in vivo when compared with late administration (24 hours post-TBI). METHODS: CD1 male mice (n = 35) were randomized to severe TBI (injury by controlled cortical impact; injury: velocity, 6 m/s; depth, 1 mm; diameter, 3 mm) or sham craniotomy followed by intravenous saline (placebo) at 1 hour, or TXA (30 mg/kg) at 1 hour or 24 hours. At 48 hours, in vivo pial intravital microscopy visualized live penumbral LEU-EC interactions and BBB microvascular fluorescent albumin leakage. Neuroclinical recovery was assessed by the Garcia Neurological Test (motor, sensory, reflex, and balance assessments) and body weight loss recovery at 1 and 2 days after injury. Analysis of variance with Bonferroni correction assessed intergroup differences ( p < 0.05). RESULTS: One-hour, but not 24-hour, TXA improved Garcia Neurological Test performance on day 1 post-TBI compared with placebo. Both 1 hour and 24 hours TXA similarly improved day 1 weight loss recovery, but only 1 hour TXA significantly improved weight loss recovery on day 2 compared with placebo ( p = 0.04). No intergroup differences were found in LEU rolling or adhesion between injured animal groups. Compared with untreated injured animals, only TXA at 1 hour reduced BBB permeability. CONCLUSION: Only early post-TBI TXA consistently improves murine neurological recovery. Tranexamic acid preserves BBB integrity but only when administered early. This effect appears independent of LEU-EC interactions and demonstrates a time-sensitive effect that supports only early TXA administration.


Assuntos
Antifibrinolíticos , Edema Encefálico , Lesões Encefálicas Traumáticas , Ácido Tranexâmico , Animais , Masculino , Camundongos , Antifibrinolíticos/farmacologia , Antifibrinolíticos/uso terapêutico , Barreira Hematoencefálica , Edema Encefálico/prevenção & controle , Lesões Encefálicas Traumáticas/tratamento farmacológico , Ácido Tranexâmico/farmacologia , Ácido Tranexâmico/uso terapêutico , Redução de Peso
15.
Prog Neurobiol ; 217: 102332, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35870679

RESUMO

During development, half of brain white matter axons are maintained for growth, while the remainder undergo developmental axon degeneration. After traumatic brain injury (TBI), injured axons also appear to follow pathways leading to either degeneration or repair. These observations raise the intriguing, but unexamined possibility that TBI recapitulates developmental axonal programs. Here, we examined axonal changes in the developing brain in young rats and after TBI in adult rat. Multiple shared changes in axonal microtubule (MT) through tubulin post-translational modifications and MT associated proteins (MAPs), tau and MAP6, were found in both development and TBI. Specifically, degenerating axons in both development and TBI underwent phosphorylation of tau and excessive tubulin tyrosination, suggesting MT instability and depolyermization. Conversely, nearby axons without degenerating morphologies, had increased MAP6 expression and maintenance of tubulin acetylation, suggesting enhanced MT stabilization, thereby supporting survival or repair. Quantitative proteomics revealed similar signaling pathways of axon degeneration and growth/repair, including protein clusters and networks. This comparison approach demonstrates how focused evaluation of developmental processes may provide insight into pathways initiated by TBI. In particular, the data suggest that TBI may reawaken dormant axonal programs that direct axons towards either degeneration or growth/repair, supporting further study in this area.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Substância Branca , Animais , Axônios/metabolismo , Lesões Encefálicas/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Ratos , Tubulina (Proteína)/metabolismo , Substância Branca/metabolismo
16.
Mil Med ; 186(Suppl 1): 601-609, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33499439

RESUMO

INTRODUCTION: Blast overpressure exposure, an important cause of traumatic brain injury (TBI), may occur during combat or military training. TBI, most commonly mild TBI, is considered a signature injury of recent combat in Iraq and Afghanistan. Low intensity primary blast-induced TBI (bTBI), caused by exposure to an explosive shock wave, commonly leaves no obvious physical external signs. Numerous studies have been conducted to understand its biological effects; however, the role of shock wave energy as related to bTBI remains poorly understood. This report combines shock wave analysis with established biological effects on the mouse brain to provide insights into the effects of shock wave physics as related to low intensity bTBI outcomes from both open-air and shock tube environments. METHODS: Shock wave peak pressure, rise time, positive phase duration, impulse, shock velocity, and particle velocity were measured using the Missouri open-air blast model from 16 blast experiments totaling 122 mice to quantify physical shock wave properties. Open-air shock waves were generated by detonating 350-g 1-m suspended Composition C-4 charges with targets on 1-m elevated stands at 2.15, 3, 4, and 7 m from the source. RESULTS: All mice sustained brain injury with no observable head movement, because of mice experiencing lower dynamic pressures than calculated in shock tubes. Impulse, pressure loading over time, was found to be directly related to bTBI severity and is a primary shock physics variable that relates to bTBI. DISCUSSION: The physical blast properties including shock wave peak pressure, rise time, positive phase duration, impulse, shock velocity, and particle velocity were examined using the Missouri open-air blast model in mice with associated neurobehavioral deficits. The blast-exposed mice sustained ultrastructural abnormalities in mitochondria, myelinated axons, and synapses, implicating that primary low intensity blast leads to nanoscale brain damage by providing the link to its pathogenesis. The velocity of the shock wave reflected back from the target stand was calculated from high-speed video and compared with that of the incident shock wave velocity. Peak incident pressure measured from high sample rate sensors was found to be within 1% of the velocity recorded by the high-speed camera, concluding that using sensors in or close to an animal brain can provide useful information regarding shock velocity within the brain, leading to more advanced knowledge between shock wave physics and tissue damage that leads to bTBIs.


Assuntos
Lesões Encefálicas Traumáticas , Afeganistão , Animais , Modelos Animais de Doenças , Iraque , Camundongos , Missouri , Física
17.
Front Neurol ; 12: 818169, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35095749

RESUMO

Most traumatic brain injuries (TBIs) during military deployment or training are clinically "mild" and frequently caused by non-impact blast exposures. Experimental models were developed to reproduce the biological consequences of high-intensity blasts causing moderate to severe brain injuries. However, the pathophysiological mechanisms of low-intensity blast (LIB)-induced neurological deficits have been understudied. This review provides perspectives on primary blast-induced mild TBI models and discusses translational aspects of LIB exposures as defined by standardized physical parameters including overpressure, impulse, and shock wave velocity. Our mouse LIB-exposure model, which reproduces deployment-related scenarios of open-field blast (OFB), caused neurobehavioral changes, including reduced exploratory activities, elevated anxiety-like levels, impaired nesting behavior, and compromised spatial reference learning and memory. These functional impairments associate with subcellular and ultrastructural neuropathological changes, such as myelinated axonal damage, synaptic alterations, and mitochondrial abnormalities occurring in the absence of gross- or cellular damage. Biochemically, we observed dysfunctional mitochondrial pathways that led to elevated oxidative stress, impaired fission-fusion dynamics, diminished mitophagy, decreased oxidative phosphorylation, and compensated cell respiration-relevant enzyme activity. LIB also induced increased levels of total tau, phosphorylated tau, and amyloid ß peptide, suggesting initiation of signaling cascades leading to neurodegeneration. We also compare translational aspects of OFB findings to alternative blast injury models. By scoping relevant recent research findings, we provide recommendations for future preclinical studies to better reflect military-operational and clinical realities. Overall, better alignment of preclinical models with clinical observations and experience related to military injuries will facilitate development of more precise diagnosis, clinical evaluation, treatment, and rehabilitation.

18.
Zhonghua Yi Xue Za Zhi ; 90(7): 458-61, 2010 Feb 23.
Artigo em Zh | MEDLINE | ID: mdl-20368068

RESUMO

OBJECTIVE: To discuss the effect of the new target controlled infusion (TCI) system in Chinese children undergoing minor operation and compared with TCI system with Marsh parameters. METHODS: Ninety ASA I, aged 3 - 5 yrs children undergoing elective unilateral high ligation of hernial sac under general anesthesia were randomly divided into group L (n = 45) and group M (n = 45) 2 groups. All subjects were unpremedicated. Systolic blood pressure (SBP), diastolic blood pressure (DBP), ECG, SpO2 and BIS were monitored. Patients of Group L and group M were anesthetized with propofol by Lian propofol TCI system and Marsh system respectively, combined with regional block. The target plasma concentration of TCI system was set at 6 microg/ml initially and up-regulated 1 microg/ml gradually if obvious body movement occurred while skin incision. If the target plasma concentration up to 8 microg/ml but there still had body movement, the TCI venous anesthesia was replaced by inhaled anesthesia. HR, RR, SBP, DBP and BIS were recorded in time points of baseline (T(0)), after the induction (T(1)), skin incision (T(2)), 3, 5 min after skin incision (T(3), T(4)), the end of operation (T(5)). Complications, the awakening time and the number of cases which anesthetized with different propofol plasma concentrations or inhaled anesthesia were recorded respectively as well. RESULTS: The number of cases which completed the operation under TCI plasma concentration 6 microg/ml in group L were significantly more than those in group M (P < 0.01). There were significantly different of T(1)-T(4) values of HR, RR, SBP, DBP and BIS in group M (P < 0.05), but not in group L. Compared with group L, T(2)-T(4) values of HR, RR, SBP, DBP and BIS were higher in group M (P < 0.05 or 0.01). Complications were lower in group L than those in group M. CONCLUSION: Compared with Marsh system, propofol 6 microg/ml plasma concentration with the new target controlled infusion system applied in Chinese children undergoing unilateral high ligation of hernial sac could maintain stable hemodynamics, less stress reaction and complications.


Assuntos
Sistemas de Liberação de Medicamentos , Hérnia Inguinal/cirurgia , Propofol/administração & dosagem , Pré-Escolar , Feminino , Humanos , Masculino , Propofol/farmacologia
19.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 30(3): 264-7, 2010 Mar.
Artigo em Zh | MEDLINE | ID: mdl-20535923

RESUMO

OBJECTIVE: To assess the condition of myocardial injury after cardiopulmonary bypass (CPB) and the effects of breviscapine (BVC) on cardiac function in children undergoing open heart surgery. METHODS: Thirty-six children (ASA II or III, aged 2-65 months) scheduled to receive ventricular septal defect repairing were randomly assigned to three groups, the control group treated with saline, and the BVC treated groups treated respectively with low dose (0.5 mg/kg) and high dose (1.0 mg/kg) BVC, 12 patients in each group. Saline or BVC (in volume of 15 mL) was administered intravenously after induction of anesthesia with micro-pump within 30 min. Blood levels of troponin I (cTn-I ) and malondialdehyde (MDA) were measured at different time points: pre-operation (T0), during aortic unclamping (T1), and 30 min, 1 h, 6 h, 24 h after aortic unclamping (T2, T3, T4, T5). And the time of operation, CPB, aortic unclamping, and the condition of drainage in 24 h after operation as well as the dosages of narcotics (midazolam, propofol and fentanyl) used were recorded. RESULTS: No significant difference among groups was found in terms of sex ratio, age, body weight, time of aortic unclamping, CPB and operation, as well as the dosages of narcotics used and the volume of post-operation drainage. Compared with baseline (T0), levels of cTn-I at T1, T4 and T5 increased significantly in all three groups (P<0.01), with the peak revealed at T4; cTn-I in the control group were higher than those in the low dose BVC treated group at T1 and T4 (P<0.01), and those in the high dose BVC group at T1, T4, and T5, while it was insignificantly different between the two BVC treated groups. Level of plasmal MDA began to rise in all groups at T1 with the peak revealed at T2, it lowered after then, and reached the baseline at T5; comparison between groups showed that it was lower in the BVC treated groups than in the control group at T1-T4. CONCLUSIONS: Different degree of cardiac injury always happens after open heart surgery and CPB, showing high level of cTn- I within 24 h with the peak revealed at 6 h after aortic unclamping. Intravenous perfusion BVC before CPB at the dose of 0.5 or 1 mg/kg could protect the cardiac function to some extent.


Assuntos
Ponte Cardiopulmonar/efeitos adversos , Flavonoides/administração & dosagem , Malondialdeído/sangue , Troponina I/sangue , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Flavonoides/uso terapêutico , Humanos , Lactente , Masculino , Período Pós-Operatório
20.
Exp Ther Med ; 19(2): 1554-1559, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32010338

RESUMO

Garlic (Allium sativum) has been widely used for culinary and medicinal purposes. Aged garlic extract (AGE) and sulfur-containing compounds, including S-allylcysteine (SAC) are well documented botanical active components of garlic. AGE is prepared by the prolonged extraction of fresh garlic with aqueous ethanol and is considered a nutritional supplement with potential to promote human health. SAC is a water-soluble organosulfur compound and the most abundant component of AGE. Studies have demonstrated that both AGE and SAC can exert neuroprotective effects against neuroinflammation and neurodegeneration. Another bioactive component in AGE is N-α-(1-deoxy-D-fructos-1-yl)-L-arginine (FruArg) although less is known about the metabolic activity of this compound. The main aim of this review was to provide an undated overview of the neuroprotective perspectives of these active garlic components (AGE, SAC and FruArg). Of interest, our studies and those of others indicate that both AGE and FruArg are involved in the regulation of gene transcription and protein expression. AGE has been shown to reverse 67% of the transcriptome alteration induced by endotoxins-lipopolysaccharide (LPS), and FruArg has been shown to account for the protective effects by reversing 55% of genes altered in a cell-based neuroinflammation paradigm stimulated by LPS in murine BV-2 microglial cells. AGE and FruArg can alleviate neuroinflammatory responses through a variety of signaling pathways, such as Toll-like receptor and interleukin (IL)-6 signaling, as well as by upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated oxidative stress pathways known to promote microglial resiliency against neuroinflammation and neurodegeneration. The capability of FruArg to pass through the blood-brain barrier further supports its potential as a therapeutic compound. In summary, these experimental results provide new insight into the understanding of the neuroprotective effects of garlic components in promoting brain resiliency for health benefits.

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