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1.
Neurobiol Dis ; 172: 105836, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-35932990

RESUMEN

Recent bodies of work in regard to stroke have revealed significant sex differences in terms of risk and outcome. While differences in sex hormones have been the focus of earlier research, the reasons for these differences are much more complex and require further identification. This review covers differences in sex related immune responses with a focus on differences in immune cell composition and function. While females are more susceptible to immune related diseases, they seem to have better outcomes from stroke at the experimental level with reduced pro-inflammatory responses. However, at the clinical level, the picture is much more complex with worse neurological outcomes from stroke. While the use of exogenous sex steroids can replicate some of these findings, it is apparent that many other factors are involved in the modulation of immune responses. As a result, more research is needed to better understand these differences and identify appropriate interventions and risk modification.


Asunto(s)
Caracteres Sexuales , Accidente Cerebrovascular , Susceptibilidad a Enfermedades , Femenino , Humanos , Inmunidad , Masculino
2.
bioRxiv ; 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38895236

RESUMEN

Type 2 diabetes mellitus (T2DM) is associated with poor outcome after stroke. Peripheral monocytes play a critical role in the secondary injury and recovery of damaged brain tissue after stroke, but the underlying mechanisms are largely unclear. To investigate transcriptome changes and molecular networks across monocyte subsets in response to T2DM and stroke, we performed single-cell RNA-sequencing (scRNAseq) from peripheral blood mononuclear cells and bulk RNA-sequencing from blood monocytes from four groups of adult mice, consisting of T2DM model db/db and normoglycemic control db/+ mice with or without ischemic stroke. Via scRNAseq we found that T2DM expands the monocyte population at the expense of lymphocytes, which was validated by flow cytometry. Among the monocytes, T2DM also disproportionally increased the inflammatory subsets with Ly6C+ and negative MHC class II expression (MO.6C+II-). Conversely, monocytes from control mice without stroke are enriched with steady-state classical monocyte subset of MO.6C+II+ but with the least percentage of MO.6C+II- subtype. Apart from enhancing inflammation and coagulation, enrichment analysis from both scRNAseq and bulk RNAseq revealed that T2DM specifically suppressed type-1 and type-2 interferon signaling pathways crucial for antigen presentation and the induction of ischemia tolerance. Preconditioning by lipopolysaccharide conferred neuroprotection against ischemic brain injury in db/+ but not in db/db mice and coincided with a lesser induction of brain Interferon-regulatory-factor-3 in the brains of the latter mice. Our results suggest that the increased diversity and altered transcriptome in the monocytes of T2DM mice underlie the worse stroke outcome by exacerbating secondary injury and potentiating stroke-induced immunosuppression. Significance Statement: The mechanisms involved in the detrimental diabetic effect on stroke are largely unclear. We show here, for the first time, that peripheral monocytes have disproportionally altered the subsets and changed transcriptome under diabetes and/or stroke conditions. Moreover, genes in the IFN-related signaling pathways are suppressed in the diabetic monocytes, which underscores the immunosuppression and impaired ischemic tolerance under the T2DM condition. Our data raise a possibility that malfunctioned monocytes may systemically and focally affect the host, leading to the poor outcome of diabetes in the setting of stroke. The results yield important clues to molecular mechanisms involved in the detrimental diabetic effect on stroke outcome.

4.
Aging Dis ; 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38029397

RESUMEN

Type 2 diabetes mellitus (T2DM) increases the risk of neurological diseases, yet how brain oscillations change as age and T2DM interact is not well characterized. To delineate the age and diabetic effect on neurophysiology, we recorded local field potentials with multichannel electrodes spanning the somatosensory cortex and hippocampus (HPC) under urethane anesthesia in diabetic and normoglycemic control mice, at 200 and 400 days of age. We analyzed the signal power of brain oscillations, brain state, sharp wave associate ripples (SPW-Rs), and functional connectivity between the cortex and HPC. We found that while both age and T2DM were correlated with a breakdown in long-range functional connectivity and reduced neurogenesis in the dentate gyrus and subventricular zone, T2DM further slowed brain oscillations and reduced theta-gamma coupling. Age and T2DM also prolonged the duration of SPW-Rs and increased gamma power during SPW-R phase. Our results have identified potential electrophysiological substrates of hippocampal changes associated with T2DM and age. The perturbed brain oscillation features and diminished neurogenesis may underlie T2DM-accelerated cognitive impairment.

5.
bioRxiv ; 2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37292743

RESUMEN

Type 2 diabetes mellitus (T2DM) increases the risk of neurological diseases, yet how brain oscillations change as age and T2DM interact is not well characterized. To delineate the age and diabetic effect on neurophysiology, we recorded local field potentials with multichannel electrodes spanning the somatosensory cortex and hippocampus (HPC) under urethane anesthesia in diabetic and normoglycemic control mice, at 200 and 400 days of age. We analyzed the signal power of brain oscillations, brain state, sharp wave associate ripples (SPW-Rs), and functional connectivity between the cortex and HPC. We found that while both age and T2DM were correlated with a breakdown in long-range functional connectivity and reduced neurogenesis in the dentate gyrus and subventricular zone, T2DM further slowed brain oscillations and reduced theta-gamma coupling. Age and T2DM also prolonged the duration of SPW-Rs and increased gamma power during SPW-R phase. Our results have identified potential electrophysiological substrates of hippocampal changes associated with T2DM and age. The perturbed brain oscillation features and diminished neurogenesis may underlie T2DM-accelerated cognitive impairment.

6.
Cells ; 11(18)2022 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-36139398

RESUMEN

Formulated as a group effort of the stroke community, the transforming concept of the neurovascular unit (NVU) depicts the structural and functional relationship between brain cells and the vascular structure. Composed of both neural and vascular elements, the NVU forms the blood-brain barrier that regulates cerebral blood flow to meet the oxygen demand of the brain in normal physiology and maintain brain homeostasis. Conversely, the dysregulation and dysfunction of the NVU is an essential pathological feature that underlies neurological disorders spanning from chronic neurodegeneration to acute cerebrovascular events such as ischemic stroke and cerebral hemorrhage, which were the focus of this review. We also discussed how common vascular risk factors of stroke predispose the NVU to pathological changes. We synthesized existing literature and first provided an overview of the basic structure and function of NVU, followed by knowledge of how these components remodel in response to ischemic stroke and brain hemorrhage. A greater understanding of the NVU dysfunction and remodeling will enable the design of targeted therapies and provide a valuable foundation for relevant research in this area.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Isquemia Encefálica/patología , Hemorragia Cerebral , Humanos , Oxígeno , Accidente Cerebrovascular/patología
7.
Neurol Med Chir (Tokyo) ; 62(12): 566-574, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36223948

RESUMEN

Delayed cerebral vasospasms after subarachnoid hemorrhage (SAH) are a risk factor for poor prognosis after successful treatment of ruptured intracranial aneurysms. Different strategies to remove clots from the subarachnoid space and prevent vasospasms have different outcomes. Intrathecal urokinase infusion therapy combined with endovascular treatment (EVT) can reduce the incidence of symptomatic vasospasms. To analyze the relationship between symptomatic vasospasms and residual SAHs after urokinase infusion therapy, we retrospectively reviewed the records of 348 consecutive patients managed with EVT and intrathecal urokinase infusion therapy for aneurysmal SAH at our institution between 2010 and 2021. Among them, 163 patients met the study criteria and were classified into two groups according to the presence of residual SAH in the cisterns, Sylvian fissures, and frontal interhemispheric fissure. The incidence of symptomatic vasospasms and the clinical outcomes were assessed. In total, eight (5.0%) patients developed symptomatic vasospasms. Patients with symptomatic vasospasms had a significantly higher incidence of residual SAH in the Sylvian or frontal interhemispheric fissures than those without (P <.0001). No patient with SAHs resolved by urokinase infusion therapy developed symptomatic vasospasms. However, the two groups did not differ significantly in terms of modified Rankin scale scores at discharge. Treatment with intrathecal urokinase infusion after EVT for aneurysmal SAH can substantially reduce the risk of clinically evident vasospasms.


Asunto(s)
Aneurisma Roto , Aneurisma Intracraneal , Hemorragia Subaracnoidea , Vasoespasmo Intracraneal , Humanos , Vasoespasmo Intracraneal/etiología , Vasoespasmo Intracraneal/prevención & control , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/terapia , Activador de Plasminógeno de Tipo Uroquinasa/uso terapéutico , Estudios Retrospectivos , Cisterna Magna , Tomografía Computarizada por Rayos X/efectos adversos , Aneurisma Roto/complicaciones , Aneurisma Roto/terapia , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/terapia , Resultado del Tratamiento
8.
J Cereb Blood Flow Metab ; 42(10): 1753-1776, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35754347

RESUMEN

Brain oscillations recorded in the extracellular space are among the most important aspects of neurophysiology data reflecting the activity and function of neurons in a population or a network. The signal strength and patterns of brain oscillations can be powerful biomarkers used for disease detection and prediction of the recovery of function. Electrophysiological signals can also serve as an index for many cutting-edge technologies aiming to interface between the nervous system and neuroprosthetic devices and to monitor the efficacy of boosting neural activity. In this review, we provided an overview of the basic knowledge regarding local field potential, electro- or magneto- encephalography signals, and their biological relevance, followed by a summary of the findings reported in various clinical and experimental stroke studies. We reviewed evidence of stroke-induced changes in hippocampal oscillations and disruption of communication between brain networks as potential mechanisms underlying post-stroke cognitive dysfunction. We also discussed the promise of brain stimulation in promoting post stroke functional recovery via restoring neural activity and enhancing brain plasticity.


Asunto(s)
Ondas Encefálicas , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Encéfalo , Humanos , Plasticidad Neuronal/fisiología
9.
Microsc Microanal ; 17(2): 246-51, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21362208

RESUMEN

The elemental composition and microscopic-level shape of inclusions inside industrial materials are considered important factors in fracture analytical studies. In this work, a three-dimensional (3D) microscopic elemental analysis system based on a serial sectioning technique was developed to observe the internal structure of such materials. This 3D elemental mapping system included an X-ray fluorescence analyzer and a high-precision milling machine. Control signals for the X-ray observation process were automatically sent from a data I/O system synchronized with the precision positioning on the milling machine. Composite specimens were used to confirm the resolution and the accuracy of 3D models generated from this system. Each of the two specimens was composed of three metal wires of 0.5 mm diameter braided into a single twisted wire that was placed inside a metal pipe; the pipe was then filled with either epoxy resin or Sn. The milling machine was used to create a mirror-finish cross-sectional surface on these specimens, and elemental analyses were performed. The twisted wire structure was clearly observed in the resulting 3D models. This system enables automated investigation of the 3D internal structure of materials as well as the identification of their elemental components.

10.
NMC Case Rep J ; 8(1): 359-365, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35079489

RESUMEN

Double-lumen carotid plaque is a rare pathological condition, and only few reports about this condition have been recorded in the literature. However, no study has used endovascular therapy (EVT) for the treatment of double-lumen carotid plaque. Herein, we present a unique case of double-lumen carotid plaque associated with severe stenosis that was successfully treated with staged angioplasty (SAP). Moreover, a literature review of its pathology and other treatment options has been conducted. SAP is a two-stage carotid artery stenting (CAS) that can prevent hyperperfusion syndrome after revascularization. In this study, a 62-year-old man developed walking disturbance and left hemiparesis. Magnetic resonance imaging (MRI) revealed ischemic lesions in the watershed area of the right hemisphere and an irregular plaque in the right cervical internal carotid artery (ICA). Ultrasonography showed 84% stenosis in the area and a double lumen distal to the stenosis in the right ICA. Digital subtraction angiography (DSA) revealed a double-lumen plaque with 70% stenosis based on the North American Symptomatic Carotid Endarterectomy Trial criteria. SAP was performed after medication therapy and rehabilitation, and the surgery was uneventful. A double-lumen carotid plaque associated with severe stenosis is a rare condition with a high risk of emboli and stroke. In an unstable lesion, carotid endarterectomy is the first option. However, since the patient in this case was at high risk for general anesthesia, SAP was performed. Hence, if an appropriate device is used, EVT can be a safe treatment strategy for unstable and atypical plaques as in this case.

11.
Surg Neurol Int ; 12: 4, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33500819

RESUMEN

BACKGROUND: Chronic basilar artery dissection (BAD) is a rare pathology, and only a few reports have been mentioned in the literature. The imaging features of chronic BAD, especially those that develop into a subarachnoid hemorrhage (SAH), are unknown. CASE DESCRIPTION: We report a unique case of a chronic BAD with a split intimal flap that developed into an SAH. A 74-year-old man was diagnosed with BAD. After considering all treatment options, conservative treatment was selected for the patient. We continued imaging follow-up of the patient in our outpatient clinic once a year. The BA gradually dilated and the internal flap split. The patient and his family refused surgical treatment; therefore, conservative treatment was continued. Six years and 2 months from the first diagnosis, he developed a massive SAH and died. CONCLUSION: In the case of this patient, the weakened condition of the internal elastic lamina may have caused dissection of the intimal flap between the intima and media. Furthermore, the dissection may have developed and connected the true lumen to the pseudolumen and induced BA rupture. Thereby, split of the internal flap could be a risk factor for rupture in chronic BAD.

12.
Surg Neurol Int ; 12: 67, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33767871

RESUMEN

BACKGROUND: Skeletal muscle mass is an important factor for various diseases' outcomes. The psoas muscle cross-sectional area on the abdominal computed tomography (CT), gait speed, and handgrip strength is used to measure it. However, it is difficult to measure the neurological patients' muscle mass or function because (1) we do not perform abdominal CT. (2) Such patients have impaired consciousness, gait disturbance, paresis, and need of rest. Temporal muscle thickness (TMT) on magnetic resonance imaging (MRI) is now attractive for skeletal muscle volume indicator, but the reference values are not established. We herein investigated the standard value of the Japanese TMT using the brain check-up database by MRI. METHODS: We retrospectively investigated 360 Japanese individuals from two institutions between 2017 and 2019. We measured TMT on the T1-weighted images in the previously reported way. The associations between TMT and other variables were analyzed. RESULTS: TMT of 214 women and 146 men, ranging from 35 to 84 years old, was investigated. TMT ranged from 3.69 to 16.90 mm. Mean TMT values were significantly higher in men compared to women except for the over 70-year-old cohort. TMT was correlated to weight and body mass index in both sexes. CONCLUSION: This is the first retrospective study on the standard TMT values from the Japanese brain check-up database. Our results were just reference values, but these would be useful for further investigation in other neurosurgical and neurological diseases regarding muscle volume or sarcopenia.

13.
Neurol Med Chir (Tokyo) ; 61(3): 193-203, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33504734

RESUMEN

It is important to assess the cerebral arteries near the clip after cerebral aneurysm clipping. Contrast-enhanced computed tomography angiography has side effects of contrast medium and radiation exposure. Time-of-flight magnetic resonance angiography (TOF-MRA) is a fast and non-invasive method, but clip-induced artifact limits the assessment around the clip. Recently, 3 tesla MRA with ultrashort echo time called SILENT MRA (GE Healthcare Life Sciences, UK) has been reported to have the potential to overcome these disadvantages. We herein present consecutive 19 cerebral aneurysm patients treated by clipping and evaluated using SILENT MRA. The 19 patients (15 women and 4 men) underwent TOF-MRA and SILENT MRA during the same scan session. Two neurosurgeons independently assessed the visibility of the mother vessel at the clipping site in TOF-MRA and SILENT MRA. We also investigated the factors related to visibility in SILENT MRA. All patients' mother vessels were not described in TOF-MRA, and that of 16 patients (84%) were described in SILENT MRA. Overall agreement was 100% in the two neurosurgeons, and the fixed marginal kappa = 1.00 (95% CI: 0.36-1.00). Univariate analysis revealed that larger aneurysm dome and long clip blade length contributed to the visibility of the mother vessel in SILENT MRA. (p = 0.023, 0.007, each). In conclusion, SILENT MRA can be applied for the assessment of the arteries and aneurysm neck remnants near the clip. Using clips with long blade and ligation with its tip would be related to the visibility of the mother vessels in SILENT MRA.


Asunto(s)
Aneurisma Intracraneal , Angiografía por Resonancia Magnética , Angiografía de Substracción Digital , Arterias Cerebrales , Medios de Contraste , Femenino , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Masculino , Madres
14.
Radiol Case Rep ; 16(12): 3721-3728, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34630807

RESUMEN

In conventional carotid computed tomographic angiography, the artifacts of the stent vary depending on the structure and characteristics of the alloy type. Cobalt-based alloy stents have been reported to exhibit high artifacts, and accurate evaluation of the internal lumen can be difficult. Recently, ultra-high-resolution computed tomography scanner systems have become available for clinical practice. The primary features of this computed tomography scanner are a 0.25-mm detector row width and a 1024 × 1024 matrix. We report a case-series of carotid artery stenting using a cobalt-based alloy stent scanned by an ultra-high-resolution computed tomography scanner system and model-based iterative reconstruction. We also report that the combination of the ultra-high-resolution computed tomography scanner system with model-based iterative reconstruction would be useful to evaluate vessel patency after placement of a cobalt-based alloy stent.

15.
Surg Neurol Int ; 12: 528, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34754578

RESUMEN

BACKGROUND: The subcallosal artery (ScA) is a single dominant artery arising from the anterior communicating artery. Its injury causes amnesia and cognitive disturbance. The conventional computed tomographic angiography (C-CTA) is a common evaluation method of the intracranial artery. However, to image tinny perforating arteries such as the ScA is technically demanding for C-CTA. The purpose of this study is to investigate whether the ultra-high-resolution CTA (UHR-CTA) could image the ScA better than C-CTA. UHR-CTA became available in clinical practice in 2017. Its novel features are the improvement of the detector system and a small X-ray focus. METHODS: Between April 2019 and May 2020, 77 and 49 patients who underwent intracranial UHR-CTA and C-CTA, respectively, were enrolled in this study. Two board-certified neurosurgeons participated as observers to identify the ScA based on UHR-CTA and C-CTA images. RESULTS: UHR-CTA and C-CTA detected the ScA in 56-58% and 30-40% of the patients, respectively. In visualization of the ScA, UHR-CTA was better than C-CTA (P < 0.05, Fisher's exact test). Between the two observers, the Cohen's kappa coefficient was 0.77 for UHR-CTA and 0.78 for C-CTA. CONCLUSIONS: UHR-CTA is a simple and accessible method to evaluate intracranial vasculature. Visualization of the ScA with UHR-CTA was better than that with C-CTA. The high quality of UHR-CTA could provide useful information in the neurosurgery field.

16.
Surg Neurol Int ; 12: 212, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34084639

RESUMEN

BACKGROUND: Chronic subdural hematoma (CSDH) is usually associated with good recovery with burr hole irrigation and postoperative drainage under local anesthesia. In Japan, traffic accidents by the elderly drivers over 65 years old are severely increasing, and there is no consensus on whether or not to return to driving after CSDH treatment. We perform a postoperative cognitive assessment. We retrospectively investigated the return-to-driving rate and associated factors. METHODS: Of the 45 patients over 65 y.o. and who had usually driven, 30 patients wished to drive again. We performed tests composed of Mini-Mental State Examination (MMSE), line cancellation and line bisection task, Kohs block design test, trail making test (TMT)-A and B, Kana-hiroi test, Rey-Osterrieth complex figure test, and behavioral assessment of the dysexecutive syndrome, in order. When all tests' scores were better than the cutoff values, we let patients drive again. When some of the scores were worse than the cutoff values, we reevaluated the patients at the outpatient every month. If the patients' scores could not improve at the outpatient, we recommended them to stop driving. RESULTS: Nineteen of 30 patients could return to driving. Worse MMSE, Kohs block design test, TMT-A, TMT-B scores, higher age, dementia, or consciousness disturbance as chief complaints were associated with driving disability. CONCLUSION: CSDH is known as treatable dementia. However, we should perform an objective cognitive assessment before discharge because only 63% of the patients over 65 y.o. who wished to drive could return to driving.

17.
Cureus ; 13(7): e16588, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34466308

RESUMEN

Introduction Prediction models of functional independent measure (FIM) score after kaifukuki (convalescent) rehabilitation ward (KRW) are needed to decide the treatment strategies and save medical resources. Statistical models were reported, but their accuracies were not satisfactory. We made such prediction models using the deep learning (DL) framework, Prediction One (Sony Network Communications Inc., Tokyo, Japan). Methods Of the 559 consecutive stroke patients, 122 patients were transferred to our KRW. We divided our 122 patients' data randomly into halves of training and validation datasets. Prediction One made three prediction models from the training dataset using (1) variables at the acute care ward admission, (2) those at the KRW admission, and (3) those combined (1) and (2). The models' determination coefficients (R2), correlation coefficients (rs), and residuals were calculated using the validation dataset. Results Of the 122 patients, the median age was 71, length of stay (LOS) in acute care ward 23 (17-30) days, LOS in KRW 53 days, total FIM scores at the admission of KRW 85, those at discharge 108. The mean FIM gain and FIM efficiency were 19 and 0.417. All patients were discharged home. Model (1), (2), and (3)'s R2 were 0.794, 0.970, and 0.972. Their mean residuals between the predicted and actual total FIM scores were -1.56±24.6, -4.49±17.1, and -2.69±15.7. Conclusion Our FIM gain and efficiency were better than national averages of FIM gain 17.1 and FIM efficiency 0.187. We made DL-based total FIM score prediction models, and their accuracies were superior to those of previous statistically calculated ones. The DL-based FIM score prediction models would save medical costs and perform efficient stroke and rehabilitation medicine.

18.
Surg Neurol Int ; 12: 31, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33598347

RESUMEN

BACKGROUND: Chronologically meteorological and calendar factors were risks of stroke occurrence. However, the prediction of stroke occurrences is difficult depending on only meteorological and calendar factors. We tried to make prediction models for stroke occurrences using deep learning (DL) software, Prediction One (Sony Network Communications Inc., Tokyo, Japan), with those variables. METHODS: We retrospectively investigated the daily stroke occurrences between 2017 and 2019. We used Prediction One software to make the prediction models for daily stroke occurrences (present or absent) using 221 chronologically meteorological and calendar factors. We made a prediction models from the 3-year dataset and evaluated their accuracies using the internal cross-validation. Areas under the curves (AUCs) of receiver operating characteristic curves were used as accuracies. RESULTS: The 371 cerebral infarction (CI), 184 intracerebral hemorrhage (ICH), and 53 subarachnoid hemorrhage patients were included in the study. The AUCs of the several DL-based prediction models for all stroke occurrences were 0.532-0.757. Those for CI were 0.600-0.782. Those for ICH were 0.714-0.988. CONCLUSION: Our preliminary results suggested a probability of the DL-based prediction models for stroke occurrence only by meteorological and calendar factors. In the future, by synchronizing a variety of medical information among the electronic medical records and personal smartphones as well as integrating the physical activities or meteorological conditions in real time, the prediction of stroke occurrence could be performed with high accuracy, to save medical resources, to have patients care for themselves, and to perform efficient medicine.

19.
Mol Pharmacol ; 77(4): 704-13, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20097776

RESUMEN

Sphingosine 1-phosphate (S1P) induces diverse biological responses in various tissues by activating specific G protein-coupled receptors (S1P(1)-S1P(5) receptors). The biological signaling regulated by S1P(3) receptor has not been fully elucidated because of the lack of an S1P(3) receptor-specific antagonist or agonist. We developed a novel S1P(3) receptor antagonist, 1-(4-chlorophenylhydrazono)-1-(4-chlorophenylamino)-3,3-dimethyl- 2-butanone (TY-52156), and show here that the S1P-induced decrease in coronary flow (CF) is mediated by the S1P(3) receptor. In functional studies, TY-52156 showed submicromolar potency and a high degree of selectivity for S1P(3) receptor. TY-52156, but not an S1P(1) receptor antagonist [(R)-phosphoric acid mono-[2-amino-2-(3-octyl-phenylcarbamoyl)-ethyl] ester; VPC23019] or S1P(2) receptor antagonist [1-[1,3-dimethyl-4-(2-methylethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl]-4-(3,5-dichloro-4-pyridinyl)-semicarbazide; JTE013], inhibited the decrease in CF induced by S1P in isolated perfused rat hearts. We further investigated the effect of TY-52156 on both the S1P-induced increase in intracellular calcium ([Ca(2+)](i)) and Rho activation that are responsible for the contraction of human coronary artery smooth muscle cells. TY-52156 inhibited both the S1P-induced increase in [Ca(2+)](i) and Rho activation. In contrast, VPC23019 and JTE013 inhibited only the increase in [Ca(2+)](i) and Rho activation, respectively. We further confirmed that TY-52156 inhibited FTY-720-induced S1P(3) receptor-mediated bradycardia in vivo. These results clearly show that TY-52156 is both sensitive and useful as an S1P(3) receptor-specific antagonist and reveal that S1P induces vasoconstriction by directly activating S1P(3) receptor and through a subsequent increase in [Ca(2+)](i) and Rho activation in vascular smooth muscle cells.


Asunto(s)
Hidrazonas/farmacología , Lisofosfolípidos/farmacología , Receptores de Lisoesfingolípidos/antagonistas & inhibidores , Receptores de Lisoesfingolípidos/fisiología , Esfingosina/análogos & derivados , Vasoconstricción/efectos de los fármacos , Animales , Células CHO , Calcio/metabolismo , Arterias Cerebrales/efectos de los fármacos , Arterias Cerebrales/fisiología , Circulación Coronaria/efectos de los fármacos , Cricetinae , Cricetulus , Perros , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Clorhidrato de Fingolimod , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Fosforilación , Glicoles de Propileno/farmacología , Ratas , Ratas Sprague-Dawley , Esfingosina/farmacología , Quinasas Asociadas a rho/fisiología
20.
NMC Case Rep J ; 7(1): 39-41, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31938681

RESUMEN

Cystic tumors, such as craniopharyngiomas and Rathke's cleft cysts, as well as arachnoid cysts have been reported to rupture occasionally. Approximately 8-10% of glioblastomas (GBMs) are known to have a significant cystic component; however, to the best of our knowledge, no studies have reported cystic rupturing of GBMs. Here, we describe a unique case of cystic GBM rupturing and penetrating into the cerebral ventricle. A 77-year-old man with a right frontal lobe lesion suspected as GBM with a large cyst was referred to our hospital. At admission, disorientation and left facial weakness were detected. Consciousness disturbance worsened on the 8th day of hospitalization. Computed tomography (CT) revealed prominent shrinkage of the tumor and intratumoral cyst. Signs of meningeal irritation were observed, and chemical meningitis due to cystic tumor rupture and leakage of necrotic components into the ventricle was highly suspected. Surgical resection of the right frontal lobe tumor was performed on the 10th day of hospitalization. During the surgery, clear and colorless cerebrospinal fluid was obtained upon penetration of the tumoral cyst, suggesting traffic of tumor cysts and cerebral ventricle. Adjuvant chemoradiation therapy was initiated postoperatively. Local recurrence was noted at the corpus callosum 7 months postoperatively and was treated with a gamma knife. Further therapy was performed after this recurrence. However, his condition gradually deteriorated 15 months postoperatively, and he was subjected to terminal care. To the best of our knowledge, this is the first report on a cystic GBM rupture.

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