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1.
J Thorac Dis ; 15(9): 5029-5036, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37868868

RESUMO

Background: Aortic coarctation (CoA) is a common congenital aortic disease, which is often accompanied by aortic root disease. This study aimed to explore the simultaneous surgical treatment of aortic root replacement and ascending-abdominal aortic bypass grafting for patients with CoA and aortic root disease. Case Description: From June 2014 to December 2019, nine patients with CoA and aortic root disease underwent simultaneous surgical treatment involving ascending-abdominal aortic bypass grafting and aortic root replacement (Bentall operation in eight patients and Wheat's operation in one patient). The degree of constriction, cardiopulmonary bypass time, ascending aorta occlusion time, operation time, artificial vessel diameter, ventilator support time and blood loss were recorded and analyzed. The blood pressure data of the limbs were measured pre- and postoperatively. All patients were followed up for 24±7 months. The mean extracorporeal circulation time was 130±17 minutes. The mean duration of the aortic clamp occlusion was 85±14 minutes. The mean operation time was 6.2±1.9 hours. The mean blood loss during and after surgery was 1,958±849 mL. The mean ventilator support time after operation was 20.3±11.6 hours. There were no operative mortalities. The arterial pressure gradient in the upper and lower limbs significantly improved. Postoperative computer-enhanced transvenous angiograms showed that the grafts were open with fluent flow. None of the patients experienced gastrointestinal complications, and no adverse events were observed during the follow-up. Conclusions: Simultaneous surgical treatment with ascending-to-abdominal aorta bypass grafting and aortic root replacement is feasible for patients with CoA and aortic root disease.

2.
Neurocrit Care ; 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37848656

RESUMO

BACKGROUND: The objective of this research was to examine the impact of the monocyte-to-lymphocyte ratio (MLR) on the advancement of hematoma after cerebral contusion. METHODS: The clinical information and laboratory test findings of people with cerebral contusion were retrospectively analyzed. Using the tertiles of MLR, the study participants were categorized into three groups, enabling the evaluation of the correlation between MLR and the advancement of hematoma after cerebral contusion. RESULTS: Among the cohort of patients showing progression, MLR levels were significantly higher compared with the nonprogress group (P < 0.001). The high MLR group had a significantly higher proportion of patients with hematoma progression compared with the medium and low MLR groups. However, the medium MLR group had a lower proportion of patients with hematoma progression compared with the low MLR group. High MLR levels were independently linked to a higher risk of hematoma progression (Odds Ratio 3.546, 95% Confidence Interval 1.187-10.597, P = 0.024). By incorporating factors such as Glasgow Coma Scale score on admission, anticoagulant/antiplatelet therapy, white blood cell count, and MLR into the model, the predictive performance of the model significantly improved (area under the curve 0.754). CONCLUSIONS: Our study suggests that MLR may serve as a potential indicator for predicting the progression of hematoma after cerebral contusion. Further research is necessary to investigate the underlying pathological and physiological mechanisms that contribute to the association between MLR and the progression of hematoma after cerebral contusion and to explore its clinical implications.

3.
Opt Lett ; 47(19): 4945-4948, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36181157

RESUMO

Stimulated Raman transitions are often used in an atom interferometer (AI) for wave packet manipulation. Normally, two lasers with different frequencies contained in a Raman beam are combined first and then amplified by a single tapered amplifier (TA). This configuration can simplify the laser system of the AI, however, additional sidebands will be generated by the TA because of the nonlinear effect in the TA. In this work, the impact of additional sidebands generated with a single TA on the AI is studied. We first observe the additional sidebands in a Raman laser by a Fabry-Pérot interferometer (FPI), and the additional sidebands will be greatly suppressed by reducing the injection laser power of the TA. This is also confirmed by observing the position-dependent Raman transitions induced by additional sidebands at different injection power in an AI. However, the phase shifts induced by additional sidebands are not reduced obviously when the injection power of the TA is reduced. Therefore, it is necessary to separately amplify two lasers contained in the Raman laser by two TAs for a high precision AI. The spectroscopy of Raman laser generated by two TAs is also measured by the FPI, and the impact of additional sidebands on the AI is eliminated. This work has guiding significance for the design of the laser system in a high-precision AI.

4.
Opt Express ; 30(7): 10723-10731, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35473032

RESUMO

Precise information of positions and sizes of atom clouds is required for atom-interferometry-based G measurements. In this work, characterizing atom clouds using a charge-coupled device (CCD) is presented. The parameters of atom clouds are extracted from fluorescence images captured by the CCD. For characterization, in-situ calibration of the magnification of the imaging system is implemented using the free-fall distance of atom clouds as the dimension reference. Moreover, influence of the probe beam on measuring the positions of atom clouds is investigated, and a differential measurement by reversing the direction of the probe beam is proposed to suppress the influence. Finally, precision at sub-mm level for characterizing atom clouds is achieved.

5.
Rev Sci Instrum ; 93(4): 044503, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35489930

RESUMO

Vibration correction provides a simple and flexible method of suppressing ambient vibration noise in transportable atom gravimeters. However, in the seismometers used for vibration correction, a spurious output may be induced by the magnetic field of the magnetic-optical trap, introducing errors to the gravity measurements. This paper evaluates the influence of the magnetic field on the seismometer and the corresponding errors in the gravity measurements. It is found that an error level of order 10 µGal may be present if the seismometer is not configured carefully. The dependence of the influence on the orientation of the seismometer and the lasting time of the magnetic field are investigated. The effective suppression of the influence by shielding the seismometer is also demonstrated. Our results focus attention on the possible errors related to seismometers in high-precision gravity measurements by using atom gravimeters.

6.
Opt Lett ; 47(1): 114-117, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34951896

RESUMO

The additional sidebands (ASBs) in a Raman laser will have a significant effect on the performance of atom gravimeters (AGs) based on phase-modulated Raman lasers. We propose a method of modulating the sideband-to-carrier ratio in Raman lasers to determine the magic time intervals where the phase shift induced by the ASB effect is minimized, and this method is demonstrated by experiments. Among these magic time intervals, some noise-immunity points are predicted. Based on the prediction and the result of the ASB effect changing with the interval time T between adjacent Raman pulses, an optimal magic time interval is selected. Therefore, the uncertainty to the gravity measurement induced by the ASB effect when the AG works at the magic time interval is reduced to 0.5 µGal. Furthermore, the ASB effect and its zero-phase points in four-pulse atom interferometers are also discussed. This work provides a clear way to eliminate the phase shift induced by the ASB effect in high-precision AGs employing phase-modulated Raman lasers.

7.
Rev Sci Instrum ; 92(5): 053202, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34243337

RESUMO

As part of a program to determine the gravitational constant G using multiple independent methods in the same laboratory, an atom gravity gradiometer is being developed. The gradiometer is designed with two magneto-optical traps to ensure both the fast simultaneous launch of two atomic clouds and an optimized configuration of source masses. Here, the design of the G measurement by atom interferometry is detailed, and the experimental setup of the atom gravity gradiometer is reported. A preliminary sensitivity of 3 × 10-9 g/Hz to differential gravity acceleration is obtained, which corresponds to 99 E/Hz (1 E = 10-9 s-2) for the gradiometer with a baseline of 0.3 m. This provides access to measuring G at the level of less than 200 parts per million in the first experimental stage.

8.
Rev Sci Instrum ; 92(6): 063202, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34243513

RESUMO

As the existence of the gravity gradient, the output of gravimeters is actually the gravitational acceleration at the reference instrumental height. Precise knowledge of the reference height is indispensable in the utilization of gravity measurements, especially for absolute gravimeters. Here, we present an interferometric method to measure the distance between the atomic cloud and a reflecting mirror directly, which consequently determines the reference height of our atom gravimeter. This interferometric method is based on a frequency jump of Raman lasers applied at the π pulse of the atom interferometer, which induces an additional phase shift proportional to the interested distance. An uncertainty of 2 mm is achieved here for the distance measurement, and the effect of the gravity gradient on absolute gravity measurements can thus be constrained within 1 µGal. This work provides a concrete-object-based measurement of the reference height for atom gravimeters.

9.
Opt Express ; 28(8): 12189-12200, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32403717

RESUMO

We present a matter wave gyroscope with a Sagnac area of 5.92 cm2, achieving a short-term sensitivity of 167 nrad/s/Hz1/2. The atom interferometry gyroscope is driven by a π/2 - π - π - π/2 Raman pulse sequence based on an atom fountain with a parabolic trajectory. The phase-locked laser beams for Raman transitions partly propagate outside of the vacuum chamber and expose to the air when passing through the two arms of the vacuum chamber. This configuration leads to the tilt of the laser's wave-front and suffers the fluctuation of air density. The impacts on both the fringe contrast and long-term stability are experimentally investigated in detail, and effective schemes are developed to improve the performance of our atom gyroscope. The method presented here could be useful for developing large atom interferometry facilities with separated vacuum chambers.

10.
Front Neurol ; 11: 551411, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33510702

RESUMO

This study aims at evaluating the importance and its underlying mechanism of the cluster of microRNA-144/451 (miR-144/451) in the models with intracerebral hemorrhage (ICH). A model of collagenase-induced mice with ICH and a model of mice with simple miR-144/451 gene knockout (KO) were used in this study. Neurodeficits and the water content of the brain of the mice in each group were detected 3 days after collagenase injection. The secretion of proinflammatory cytokines, such as tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß), as well as certain biomarkers of oxidative stress, was determined in this study. The results revealed that the expression of miR-451 significantly decreased in the mice with ICH, whereas miR-144 showed no significant changes. KO of the cluster of miR-144/451 exacerbated the neurological deficits and brain edema in the mice with ICH. Further analyses demonstrated that the KO of the cluster of miR-144/451 significantly promoted the secretion of TNF-α and IL-1ß and the oxidative stress in the perihematomal region of the mice with ICH. In addition, the miR-144/451's depletion inhibited the regulatory axis' activities of miR-451-14-3-3ζ-FoxO3 in the mice with ICH. In conclusion, these data demonstrated that miR-144/451 might protect the mice with ICH against neuroinflammation and oxidative stress by targeting the pathway of miR-451-14-3-3ζ-FoxO3.

11.
Rev Sci Instrum ; 90(4): 043104, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31042969

RESUMO

A compact laser system for a portable 87Rb atom interferometry gravimeter has been demonstrated in this work. This laser system is based on frequency doubling of a single seed laser at the wavelength of 1560 nm. The frequency of the seed laser is controlled by a digital unit with an analog feedback circuit. By using this frequency control method, the frequency of the laser system can be shifted over 1 GHz. Based on this method, the Raman frequency can be locked on the F = 3 → F' = 4 transition of 85Rb atoms. Moreover, the Raman sideband and the repumping laser are generated by a phase modulator, and it can generate different laser frequencies to meet the requirements of a typical atom interferometer. Additional sidebands in the Raman beam produced from the phase modulator are optimized and reduced, allowing us to observe atom interference with a free evolution time of 320 ms. The control unit including the laser system has been integrated into a box with a volume of 1.5 m × 0.6 m × 0.6 m, and the weight of which is only 150 kg. Using this compact optical scheme, our atomic gravimeter has achieved a sensitivity of 53 µGal/Hz1/2 and a resolution of better than 1 µGal (1 µGal = 1 × 10-8 m/s2) in an integration time of 3000 s.

12.
J Cereb Blood Flow Metab ; 39(8): 1588-1601, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-29513122

RESUMO

Postsynaptic density protein-95 (PSD95) plays important roles in the formation, differentiation, remodeling, and maturation of neuronal synapses. This study is to estimate the potential role of PSD95 in cognitive dysfunction and synaptic injury following intracerebral hemorrhage (ICH). The interaction between PSD95 and NMDA receptor subunit NR2B-neurotransmitter nitric oxide synthase (nNOS) could form a signal protein complex mediating excitatory signaling. Besides NR2B-nNOS, PSD95 also can bind to neurexin-1-neuroligin-1 to form a complex and participates in maintaining synaptic function. In this study, we found that there were an increase in the formation of PSD95-NR2B-nNOS complex and a decrease in the formation of neurexin-1-neuroligin-1-PSD95 complex after ICH, and this was accompanied by increased neuronal death and degeneration, and behavior dysfunction. PSD95 inhibitor Tat-NR2B9c effectively inhibited the interaction between PSD95 and NR2B-nNOS, and promoted the formation of neurexin-1-nueuroligin-1-PSD95 complex. In addition, Tat-NR2B9c treatment significantly reduced neuronal death and degeneration and matrix metalloproteinase 9 activity, alleviated inflammatory response and neurobehavioral disorders, and improved the cognitive and learning ability of ICH rats. Inhibition of the formation of PSD95-NR2B-nNOS complex can rescue secondary brain injury and behavioral cognitive impairment after ICH. PSD95 is expected to be a target for improving the prognosis of patients with ICH.


Assuntos
Hemorragia Cerebral/metabolismo , Proteína 4 Homóloga a Disks-Large/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Moléculas de Adesão Celular Neuronais/metabolismo , Hemorragia Cerebral/complicações , Hemorragia Cerebral/fisiopatologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Masculino , Neurônios/metabolismo , Neurônios/patologia , Óxido Nítrico Sintase Tipo I/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Superfície Celular/metabolismo
13.
Rev Sci Instrum ; 89(8): 083104, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30184632

RESUMO

Time is an inevitable quantity involved in absolute gravity measurements, and 10 MHz frequency standards are usually utilized as time base. Here we investigate the influence of time base bias on atom-interferometry-based gravity measurements and present an onsite calibration of the time base bias relying on an atom gravimeter itself. With a microwave source referenced to the time base, the time base bias leads to a magnified frequency shift of the microwave source output. The shift is then detected by Ramsey spectroscopy with the clock transition of 87Rb atoms as a frequency discriminator. Taking advantage of available free-fall cold atoms and developed techniques of measuring the atom energy level shift in atom gravimeters, the calibration achieves an accuracy of 0.6 mHz for the time base. And the corresponding error for gravity measurements is constrained to 0.1 µGal, meeting the requirement of state-of-the-art gravimeters. The presented evaluation is important for the applications of atom gravimeters.

14.
Rev Sci Instrum ; 89(6): 066105, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29960567

RESUMO

The vibration isolator usually plays an important role in atom interferometry gravimeters to improve their sensitivity. We show that the parasitic forced vibration of the Raman mirror, which is induced by external forces acting on the vibration isolator, can cause a bias in atom gravimeters. The mechanism of how this effect induces an additional phase shift in our interferometer is analyzed. Moreover, modulation experiments are performed to measure the dominant part of this effect, which is caused by the magnetic force between the passive vibration isolator and the coil of the magneto-optic trap. In our current apparatus, this forced vibration contributes a systematic error of -2.3(2) × 10-7 m/s2 when the vibration isolator works in the passive isolation mode. Even suppressed with an active vibration isolator, this effect can still contribute -6(1) × 10-8 m/s2; thus, it should be carefully considered in precision atom gravimeters.

15.
Curr Drug Targets ; 18(12): 1358-1366, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28460607

RESUMO

BACKGROUND: Cerebral hemorrhagic stroke, including intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and hemorrhagic transformation after cerebral infarction, is a major medical emergency in the neurology, neurosurgery, emergency and other clinical departments. The pathophysiological mechanisms of these cerebral hemorrhagic diseases have not been fully elucidated, and there are no effective pharmacological and molecular treatments against these diseases. Matrix metalloproteinase-9 (MMP-9), also known as collagenase B, is one of the most important members of the matrix metalloproteinases (MMPs) family. OBJECTIVE: This article reviews the role of MMP-9 in the pathogenesis of diseases such as brain hemorrhage, hemorrhagic transformation after cerebral infarction, SAH, and brain injury. RESULTS: The expression levels of MMP-9 in brain tissue increased after cerebral hemorrhage and related to the prognosis of brain hemorrhage. MMP-9 is related to post-thrombolytic hemorrhagic transformation after cerebral infarction. Inhibition of MMP-9 can reduce secondary brain injury after brain hemorrhage. MMP-9 aggravates the early brain injury and cerebral vasospasm after SAH. CONCLUSION: MMP-9 is involved in the pathological process of hemorrhagic stroke through a variety of mechanisms and is closely related to prognosis after cerebral hemorrhagic stroke.


Assuntos
Hemorragia Cerebral/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Acidente Vascular Cerebral/complicações , Hemorragia Subaracnóidea/metabolismo , Humanos , Prognóstico , Acidente Vascular Cerebral/metabolismo , Regulação para Cima
16.
CNS Neurosci Ther ; 23(7): 554-566, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28544790

RESUMO

OBJECTIVES: This study aimed to evaluate the roles of autophagy and endoplasmic reticulum (ER) stress in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) in rats. METHODS: Autophagy inducer (rapamycin) and inhibitor (3-methyladenine), as well as ER stress activator (tunicamycin, TM) and inhibitor (tauroursodeoxycholic acid, TUDCA), were used. Bafilomycin A1, an inhibitor of autophagosome-lysosome fusion, was used to assess autophagic flux. RESULTS: Autophagy and ER stress were enhanced in the week after ICH. At 6 hours after ICH, autophagy was excessive, while the autophagic flux was damaged at 72 hours and return to be intact at 7 days after ICH. At 6 hours after ICH, ER stress induction by TM could enhance autophagy and lead to caspase 12-mediated apoptosis and neuronal degeneration, which was further aggravated by autophagy induction. At 7 days after ICH, ER stress inhibition by TUDCA still could suppress ICH-induced SBI. And, the effects of TUDCA were enhanced by autophagy induction. CONCLUSIONS: At 6 hours after ICH, excessive autophagy may participate in ER stress-induced brain injury; at 7 days after ICH, autophagy could enhance the protection of ER stress inhibitor possibly via clearing up the cell rubbish generated due to the early-stage damaged autophagic flux.


Assuntos
Autofagia/fisiologia , Encéfalo/fisiopatologia , Hemorragia Cerebral/fisiopatologia , Estresse do Retículo Endoplasmático/fisiologia , Animais , Apoptose/fisiologia , Encéfalo/patologia , Caspase 12/metabolismo , Hemorragia Cerebral/patologia , Modelos Animais de Doenças , Progressão da Doença , Masculino , Neuroproteção/fisiologia , Distribuição Aleatória , Ratos Sprague-Dawley , Fatores de Tempo
17.
J Cereb Blood Flow Metab ; 37(7): 2509-2525, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27634935

RESUMO

Annexin A1 has been reported to exert a blood-brain barrier protection. This study was designed to examine the role of annexin A1 in intracerebral hemorrhage-induced blood-brain barrier dysfunction. A collagenase intracerebral hemorrhage model was performed in adult male Sprague Dawley rats. First, a possible relationship between annexin A1 and intracerebral hemorrhage pathology was confirmed by a loss of annexin A1 in the cerebrovascular endothelium and serum of intracerebral hemorrhage rats, and the rescue effects of i.v. administration of human recombinant annexin A1 in vivo and annexin A1 overexpression in vitro on the barrier function of brain microvascular endothelial cells exposed to intracerebral hemorrhage stimulus. Second, we found that intracerebral hemorrhage significantly increased the phosphorylation ratio of annexin A1 at the serine/threonine residues. Finally, based on site-specific mutagenesis, we identified two phosphorylation sites (a) annexin A1 phosphorylation at threonine 24 is required for its interaction with actin cytoskeleton, and (b) phosphorylation at serine27 is essential for annexin A1 secretion, both of which were essential for maintaining cytoskeleton integrity and paracellular permeability. In conclusion, annexin A1 prevents intracerebral hemorrhage-induced blood-brain barrier dysfunction in threonine 24 and serine27 phosphorylation-dependent manners. Annexin A1 phosphorylation may be a self-help strategy in brain microvascular endothelial cells after intracerebral hemorrhage; however, that was almost completely abolished by the intracerebral hemorrhage-induced loss of annexin A1.


Assuntos
Anexina A1/metabolismo , Barreira Hematoencefálica/metabolismo , Hemorragia Cerebral/metabolismo , Endotélio Vascular/metabolismo , Animais , Anexina A1/sangue , Anexina A1/genética , Anexina A1/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/fisiopatologia , Linhagem Celular , Hemorragia Cerebral/fisiopatologia , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Endotélio Vascular/efeitos dos fármacos , Humanos , Masculino , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Mutagênese Sítio-Dirigida , Fosforilação , Ratos Sprague-Dawley , Proteínas Recombinantes
18.
Phys Rev Lett ; 117(2): 023001, 2016 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-27447503

RESUMO

We report a test of the universality of free fall by comparing the gravity acceleration of the ^{87}Rb atoms in m_{F}=+1 versus those in m_{F}=-1, of which the corresponding spin orientations are opposite. A Mach-Zehnder-type atom interferometer is exploited to alternately measure the free fall acceleration of the atoms in these two magnetic sublevels, and the resultant Eötvös ratio is η_{S}=(0.2±1.2)×10^{-7}. This also gives an upper limit of 5.4×10^{-6} m^{-2} for a possible gradient field of the spacetime torsion. The interferometer using atoms in m_{F}=±1 is highly sensitive to the magnetic field inhomogeneity. A double differential measurement method is developed to alleviate the inhomogeneity influence, of which the effectiveness is validated by a magnetic field modulating experiment.

19.
Oxid Med Cell Longev ; 2016: 1203285, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27190572

RESUMO

Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH). Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI) following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER) stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches.


Assuntos
Antioxidantes/uso terapêutico , Hemorragia Cerebral/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Autofagia/efeitos dos fármacos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Lesões Encefálicas/etiologia , Hemorragia Cerebral/complicações , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Estresse Oxidativo/efeitos dos fármacos
20.
Sci Rep ; 6: 23817, 2016 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-27026509

RESUMO

Previous studies have shown neuroprotective effects of hypothermia. However, its effects on subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) remain unclear. In this study, a SAH rat model was employed to study the effects and mechanisms of pramipexole-induced hypothermia on EBI after SAH. Dose-response experiments were performed to select the appropriate pramipexole concentration and frequency of administration for induction of mild hypothermia (33-36 °C). Western blot, neurobehavioral evaluation, Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-Jade B (FJB) staining were used to detect the effects of pramipexole-induced hypothermia on SAH-induced EBI, as well as to study whether controlled rewarming could attenuate these effects. Inhibitors targeting the PI3K/AKT/GSK3ß pathway were administered to determine whether the neuroprotective effect of pramipexole-induced hypothermia was mediated by PI3K/AKT/GSK3ß signaling pathway. The results showed that intraperitoneal injection of pramipexole at 0.25 body weight once per 8 hours was found to successfully and safely maintain rats at mild hypothermia. Pramipexole-induced hypothermia ameliorated SAH-induced brain cell death, blood-brain barrier damage and neurobehavioral deficits in a PI3K/AKT/GSK3ß signaling-dependent manner. Therefore, we may conclude that pramipexole-induced hypothermia could effectively inhibit EBI after SAH in rats via PI3K/AKT/GSK3ß signaling pathway.


Assuntos
Benzotiazóis/farmacologia , Fármacos Neuroprotetores/farmacologia , Hemorragia Subaracnóidea/terapia , Animais , Apoptose , Benzotiazóis/uso terapêutico , Barreira Hematoencefálica/metabolismo , Encéfalo/irrigação sanguínea , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Avaliação Pré-Clínica de Medicamentos , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipotermia Induzida , Masculino , Fármacos Neuroprotetores/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Pramipexol , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Hemorragia Subaracnóidea/metabolismo , Hemorragia Subaracnóidea/patologia
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