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1.
J Biomed Mater Res B Appl Biomater ; 104(2): 274-82, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25716009

RESUMO

Various synthetic bone substitutes have been developed to reconstruct bone defects. One of the most prevalent ceramics in bone treatment is hydroxyapatite (HA) that is a useful material as bone substitute, however, with a low rate of biodegradation. Its structure allows isomorphic cationic and anionic substitutions to be easily introduced, which can alter the crystallinity, morphology, biocompatibility, and osteoconductivity. The objective of this study was to investigate the in vitro and in vivo biological responses to strontium-containing nanostructured carbonated HA/sodium alginate (SrCHA) spheres (425<ϕ <600 µm) that were used for sinus lifts in rabbits using nanostructured carbonated HA/sodium alginate (CHA) as a reference. Cytocompatibility was determined using a multiparametric assay after exposing murine preosteoblasts to the extracts of these materials. Twelve male and female rabbits underwent bilateral sinus lift procedures and were divided into two groups (CHA or SrCHA) and in two experimental periods (4 and 12 weeks), for microscopic and histomorphometric analyses. The in vitro test revealed the overall viability of the cells exposed to the CHA and SrCHA extracts; thus, these extracts were considered cytocompatible, which was confirmed by three different parameters in the in vitro tests. The histological analysis showed chronic inflammation with a prevalence of macrophages around the CHA spheres after 4 weeks, and this inflammation decreased after 12 weeks. Bone formation was observed in both groups, and smaller quantities of SrCHA spheres were observed after 12 weeks, indicating greater bioresorption of SrCHA than CHA. SrCHA spheres are biocompatible and osteoconductive and undergo bioresorption earlier than CHA spheres.


Assuntos
Alginatos , Substitutos Ósseos , Cavidades Cranianas/cirurgia , Durapatita , Nanoestruturas/química , Estrôncio , Alginatos/química , Alginatos/farmacologia , Animais , Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos/química , Substitutos Ósseos/farmacologia , Linhagem Celular , Cavidades Cranianas/lesões , Cavidades Cranianas/metabolismo , Avaliação Pré-Clínica de Medicamentos , Durapatita/química , Durapatita/farmacologia , Feminino , Ácido Glucurônico/química , Ácido Glucurônico/farmacologia , Ácidos Hexurônicos/química , Ácidos Hexurônicos/farmacologia , Masculino , Teste de Materiais/métodos , Camundongos , Coelhos , Estrôncio/química , Estrôncio/farmacologia
3.
Magn Reson Imaging ; 28(10): 1420-30, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20817379

RESUMO

It is widely recognised that the measurement of the arterial input function (AIF) is a key issue and a major source of errors in the pharmacokinetic modelling of dynamic, contrast-enhanced magnetic resonance imaging (DCE-MRI) data, and the modality of the AIF determination is still a matter of debate. In this study we addressed the problem of the intrinsic variability of the AIF within the imaged volume of a DCE-MRI scan by systematically investigating the change in the concentration of contrast agent over time and the fit parameters of the derived vascular input function (VIF) obtained from the superior sagittal sinus (SSS) of a patient population that was scanned longitudinally during treatment for high grade glioma. From a total of 82 scanning sessions, we compared the results obtained with three different DCE-MRI protocols and between two different fitting functions. We applied a correction algorithm to the measured concentration-time curves to minimize the effect of the low temporal resolution on the VIF, and investigated the effect of this algorithm on the reproducibility. Finally, where possible, we compared the signal obtained in the SSS to the signal obtained in the middle cerebral artery. We found a good intrapatient reproducibility of both the measured gadolinium concentrations and VIF parameters, and that the variation of the parameters due to slice location within a patient was significantly lower than the intra patient variation. Intrapatient, interscan differences were significantly less marked than inter-patient differences showing a good intraclass correlation coefficient. We did encounter a MRI protocol dependence of the VIF fitting parameters. The correction algorithm significantly improved the reproducibility of the fitting parameters. These results support the idea that the use of a patient specific measured AIF, not necessarily averaged over a large volume, offers a significant benefit with respect to an external AIF or a measured cohort average AIF.


Assuntos
Cavidades Cranianas/metabolismo , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Modelos Biológicos , Compostos Organometálicos/farmacocinética , Simulação por Computador , Meios de Contraste/farmacocinética , Cavidades Cranianas/patologia , Humanos , Aumento da Imagem/métodos , Taxa de Depuração Metabólica , Modelos Estatísticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
4.
Neurosurgery ; 66(3): 560-5; discussion 565-6, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20124931

RESUMO

OBJECTIVE: The objective of this study was to define the relative contributions of three major pro- and anti-coagulation pathways (heparin-antithrombin, protein C, and tissue factor (TF)) in the thrombogenic responses that occur in large and small vessels of the brain. METHODS: Cerebral venous sinus thrombosis was induced by topical application of FeCl3 on the superior sagittal sinus, while photoactivation of fluorescein was used to induce thrombus formation in cerebral microvessels. Heparin, activated protein C (APC), and antibodies to either APC or TF were used to assess thrombogenesis in wild-type mice. Mutant mice that overexpress the endothelial protein C receptor (EPCR-tg) or with TF deficiency in Tie2-expressing endothelial cells (LTFE) were also used. RESULTS: Thrombus formation in the superior sagittal sinus of wild-type mice was attenuated by heparin and in EPCR-tg mice, while treatment with the APC antibodies enhanced thrombogenesis. Arteriolar thrombosis was largely unresponsive to the interventions studied. However, in cerebral venules, thrombosis was inhibited by heparin and in EPCR-tg mice. TF antibody treatment also inhibited venular thrombosis, with a similar attenuation noted in LTFE mice. CONCLUSION: Thrombin promotes while the APC pathway blunts thrombus formation in an experimental model of cerebral venous sinus thrombosis. TF involvement is more evident in cerebral microvascular thrombogenesis, with endothelial cell-associated TF mediating this response in venules, but not arterioles.


Assuntos
Fatores de Coagulação Sanguínea/metabolismo , Fatores de Coagulação Sanguínea/uso terapêutico , Cavidades Cranianas/efeitos dos fármacos , Trombose Intracraniana/patologia , Trombose Intracraniana/prevenção & controle , Animais , Antígenos CD/genética , Cloretos , Cavidades Cranianas/metabolismo , Dextranos , Modelos Animais de Doenças , Receptor de Proteína C Endotelial , Compostos Férricos , Fluoresceína-5-Isotiocianato/análogos & derivados , Heparina/metabolismo , Heparina/uso terapêutico , Trombose Intracraniana/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia de Vídeo/métodos , Proteína C/metabolismo , Proteína C/uso terapêutico , Receptores de Superfície Celular/genética
5.
Clin Anat ; 21(5): 389-97, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18470937

RESUMO

The cerebral venous system is poorly understood, and best appreciated under macroscopic anatomical considerations. We present an anatomical and immunohistochemical studies to better define the morphological characteristics of the junction between the great cerebral vein and the straight sinus. Twenty-five cadaveric specimens from the anatomy laboratory of the University Victor Segalen of Bordeaux were studied. The observation of the venous junctions with the straight sinus was performed under an operating microscope. The smooth muscular actin immunohistochemical staining was performed for 18 veno-sinosal junctions. Five venous junctions were observed using an electron microscope. We observed 3 different anatomic aspects: type 1 was a junction with a small elevation in its floor and a posterior thickening (14 cases); type 2 was a junction with an outgrowth on the floor like a cornice (7 cases); and type 3 was a junction presenting a nodule. Microscopic study of type 1 and 2 junctions showed a positive coloration to orceine attesting the presence of elastic fibers. Immunohistochemistry revealed the presence of smooth muscular actin and S 100 protein attesting the presence of smooth muscular fibers and nervous fibers. We observed in the ultrastructural study, a morphological progression of the endothelium. The venous orifice of the great cerebral vein into the straight sinus could be anatomically assimilated as a true "sphincter." Its function in the regulation of the cerebral blood flow needs further exploration.


Assuntos
Veias Cerebrais/anatomia & histologia , Cavidades Cranianas/anatomia & histologia , Actinas/metabolismo , Veias Cerebrais/metabolismo , Veias Cerebrais/ultraestrutura , Circulação Cerebrovascular , Cavidades Cranianas/metabolismo , Cavidades Cranianas/ultraestrutura , Dissecação , Endotélio Vascular/anatomia & histologia , Endotélio Vascular/metabolismo , Endotélio Vascular/ultraestrutura , Humanos , Músculo Liso Vascular/anatomia & histologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/ultraestrutura
6.
Surg Neurol ; 68(3): 277-84; discussion 284, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17719966

RESUMO

BACKGROUND: Venous hypertension is regarded as an important factor in the pathogenesis of dural arteriovenous fistula (DAVF). We investigate histologic reaction of dural sinus under the condition of venous hypertension using a rat venous hypertension model to present hemodynamic and immunohistochemical effect in the development of DAVF. METHODS: Twenty-four Sprague-Dawley male rats were divided into venous hypertension and control groups. Venous hypertension was induced with a left common carotid artery-external jugular vein anastomosis and an occlusion of a right posterior facial vein. Measurements of systemic mean arterial pressure, draining vein pressure (DVP), and cerebral perfusion pressure (CPP) were conducted on the next day, at 7 days, and at 28 days after surgery, and the rats were killed for histologic examinations. RESULTS: Postoperative DVP increased significantly in venous hypertension group compared to control group (35 +/- 5 vs 13 +/- 2 mm Hg, P < .05). Increased DVP remained above 30 mm Hg throughout the observation period. Postoperative CPP decreased significantly in venous hypertension group compared to control group (49 +/- 8 vs 86 +/- 9 mm Hg, P < .05). In venous hypertension group, there was a significant difference between days 1 and 28 (49 +/- 8 vs 64 +/- 8 mm Hg, P < .05). Histologic examination revealed thickening of connective tissues, proliferation of fibroblasts, and strong expression of vascular endothelial growth factor (VEGF) in endothelium under venous hypertension condition. Immunostained VEGF cells decreased significantly from day 7 to day 28 (100 +/- 16 vs 72 +/- 19 cells, P < .05). A positive correlation was observed between DVP and VEGF expression (Pearson correlation coefficient; r = 0.671, P = .0017). There was a negative correlation between CPP and immunostained VEGF cells (r = -0.702, P = .0089). CONCLUSIONS: These results suggest that venous hypertension is associated with increased expression of VEGF, and a decreased CPP may have a potential effect in VEGF expression under venous hypertension condition. These factors are speculated to play an important role in progression of DAVF.


Assuntos
Malformações Vasculares do Sistema Nervoso Central/etiologia , Cavidades Cranianas/metabolismo , Cavidades Cranianas/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Pressão Venosa/fisiologia , Animais , Circulação Cerebrovascular/fisiologia , Cavidades Cranianas/fisiopatologia , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
7.
Neurol Res ; 29(7): 727-33, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17588308

RESUMO

OBJECTIVE: The precise mechanisms responsible for the development and growth of dural arteriovenous fistula (DAVF) remain unclear, but it has been hypothesized that vascular endothelial growth factor (VEGF) might be involved in the pathogenesis. The aim of this study was to examine the expression of VEGF in the rat DAVF model. METHODS: Forty-five Sprague-Dawley rats were used in two experiments. In Experiment 1 (n = 20, including sham-operated controls), VEGF expression was analysed by Western blots in three different rat DAVF models: model I: common carotid artery-external jugular vein (CCA-EJV) anastomosis (n = 5); model II: sagittal sinus thrombosis and bipolar coagulation of the vein draining the transverse sinus (n = 5); model III: CCA-EJV anastomosis and bipolar coagulation of the vein draining the transverse sinus and sagittal sinus thrombosis to induce venous hypertension (n = 5). Based on the results of Experiment 1, Western blots were performed at weekly intervals 1, 2 and 3 weeks in Experiment 2 following induction of venous hypertension in model III (n = 5 at each time point and n = 5 sham controls); in addition, VEGF expression was immunohistochemically examined in the dura and the brain near the occluded sinus in five model III animals after 1 week. RESULTS: In Experiment 1, Western blot analysis showed barely detectable bands with molecular weights of 45 kD, corresponding to VEGF, in the sham group, but the highest level of VEGF was induced in model III, followed by models I and II (model III>model I>model II). In Experiment 2, the expression of VEGF peaked 1 week after induction of venous hypertension in model III, decreasing in a linear fashion over 2 and 3 weeks (week 1>weeks 2 and 3). The expression of immunoreactive VEGF was restricted in the connective tissue and the endothelial layer of the dura matter, cerebral cortical tissue and neurons of the basal ganglia. CONCLUSION: Our results strongly suggest a possible contribution of an angiogenic factor to the growth of DAVF. Venous ischemia by venous hypertension might be a mechanism for inducing up-regulation of angiogenic factor expression.


Assuntos
Malformações Vasculares do Sistema Nervoso Central/metabolismo , Malformações Vasculares do Sistema Nervoso Central/fisiopatologia , Cavidades Cranianas/metabolismo , Cavidades Cranianas/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular , Cavidades Cranianas/patologia , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Masculino , Artérias Meníngeas/metabolismo , Artérias Meníngeas/patologia , Artérias Meníngeas/fisiopatologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/fisiopatologia , Ratos , Ratos Sprague-Dawley , Regulação para Cima , Pressão Venosa
8.
J Neurosurg ; 106(2 Suppl): 120-5, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17330537

RESUMO

OBJECT: Hydrocephalus results from abnormal cerebrospinal fluid (CSF) volumes or flow patterns. The absorption of CSF is determined largely by pressures within veins and venous sinuses in the head and adjacent to the spine. Most surgical solutions for hydrocephalus involve diversion of excess CSF into alternative absorption sites, and most of these solutions are still suboptimal. The focus of this work has been to recreate more normal CSF absorption into the dural venous sinuses without having to directly access the superior sagittal sinus (SSS). METHODS: Intraosseous skull infusion for the purpose of accessing the SSS and the systemic venous system was tested by experimental skull infusions of tracer fluids into living large animals (14 adult pigs). Compared with control injections into an ear vein, infusions into the skull through specially designed infusion devices had similar systemic absorption characteristics. This suggested that intraosseous skull infusion in a living large animal was successful in gaining access to the SSS and systemic venous system. CONCLUSIONS: This study constitutes the first demonstration of the success of intraosseous skull infusion in gaining rapid access to the systemic venous system and it thus opens the possibility of using this strategy for diversion of CSF back into the intracranial venous system for the treatment of hydrocephalus.


Assuntos
Hidrocefalia/terapia , Infusões Intraósseas/métodos , Crânio , Absorção , Animais , Glicemia/análise , Cateteres de Demora , Cavidades Cranianas/metabolismo , Dextranos , Orelha Externa/irrigação sanguínea , Desenho de Equipamento , Veia Femoral , Fluoresceína-5-Isotiocianato/análogos & derivados , Corantes Fluorescentes , Glucose , Hidrocefalia/líquido cefalorraquidiano , Bombas de Infusão , Infusões Intravenosas , Microscopia Eletrônica de Varredura , Osso Parietal/ultraestrutura , Crânio/ultraestrutura , Suínos
9.
J Gravit Physiol ; 14(1): P77-8, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18372708

RESUMO

By means of scanning electron microscopy the ultrastructure of ependyma was studied in the brain third ventricle of the rats repeatedly exposed to 14-day tail-suspension (TS). Animals were subjected to TS for 30 days, then readapted to horizontal position during 30 days and again, repeatedly subjected to TS for 14 days simultaneously with the rats which were in TS for the first time during 14 days. Repeated TS of rats, inspite of repeated redistribution of body liquid mediums in cranial direction, results in considerably less expressed destructive changes in ultrastructure of ependymocyte cilia, then after primary 14- and 30-day TS, showing much greater cerebrospinal fluid (CSF) outflow from brain ventricles into sagittal venous sinus at postponed for a long time, repeated simulation of weightlessness effects in comparison with CSF outflow at primery one.


Assuntos
Epêndima/ultraestrutura , Elevação dos Membros Posteriores , Microscopia Eletrônica de Varredura , Terceiro Ventrículo/ultraestrutura , Adaptação Fisiológica , Animais , Líquido Cefalorraquidiano/metabolismo , Cílios/ultraestrutura , Cavidades Cranianas/metabolismo , Epêndima/metabolismo , Masculino , Ratos , Ratos Wistar , Terceiro Ventrículo/metabolismo , Fatores de Tempo
10.
Eur. j. anat ; 7(1): 23-33, mayo 2003. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-137852

RESUMO

A recent human population from Italy was analysed for the prevalence and expression of endocranial characters, as well as for the presence of some ectocranial epigenetic traits. The purpose was to provide a supplementary database for the characterisation of some features used to compare the variability of extant and extinct human groups. Many differences between males and females are the result of allometric trajectories, with males shifted to a larger size. In contrast, other features may be unrelated to size and thus interpreted as real sexual characters. The cranial base angle is slightly but significantly related to size, particularly to the vertical skull development. The digital impressions are more expressed in males but there is no evidence of a correlation with size. Arachnoid granulations show no relationship with sex, age or size. The middle meningeal vessels are extremely variable but with a general dominance of the anterior branch providing the parietal supply, and with the left system slightly more developed than the right. The middle meningeal pattern is not related to the venous sinuses pattern. Some further aspects of the expression of these features are discussed, and data for the prevalence of epigenetic traits are reported (AU)


No disponible


Assuntos
Feminino , Humanos , Masculino , Forma do Núcleo Celular/genética , Base do Crânio/anormalidades , Base do Crânio/anatomia & histologia , Prevalência , Cavidades Cranianas/citologia , Cavidades Cranianas/inervação , Itália/etnologia , Forma do Núcleo Celular/fisiologia , Base do Crânio/citologia , Base do Crânio/patologia , Cavidades Cranianas/lesões , Cavidades Cranianas/metabolismo
12.
Brain Res ; 868(1): 150-6, 2000 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-10841901

RESUMO

Previous studies have shown that cortical tissue oxygenation is impaired during hyperventilation. However, it is important to quantify the effect of hyperventilation on brain tissue PO(2) and cerebrovenous PO(2) simultaneously especially since cerebral venous oxygenation is often used to assess brain tissue oxygenation. The present study was designed to measure the sagittal sinus PO(2) (PvO(2)), brain tissue PO(2) in the thalamus (PtO(2)), and brain temperature (Bt) simultaneously during acute hyperventilation. Isoflurane-anesthetized rats were hyperventilated for 10 min during which time the arterial carbon dioxide tension (PaCO(2)) dropped from 40.3+4.9 mmHg to 23.5+2.8 mmHg. PtO(2) declined from 26.0+/-4.2 mmHg to 14.8+/-5.2 mmHg (P=0.004) while brain temperature decreased from 36.5+0.3 degrees C to 36.2+0.3 degrees C (P=0.02). However, PvO(2) and arterial blood pressure (BP) did not change during hyperventilation. The maintenance of PvO(2) when perfusion is thought to decline and PtO(2) decreases suggests that there may be a diffusion limitation, possibly due to selective perfusion. Therefore, cerebrovenous PO(2) may not give a good assessment of brain tissue oxygenation especially in conditions of acute hyperventilation, and deeper brain regions other than the cortex also show impaired tissue oxygenation following hyperventilation.


Assuntos
Circulação Cerebrovascular/fisiologia , Hiperventilação/metabolismo , Oxigênio/metabolismo , Tálamo/metabolismo , Animais , Calibragem , Cavidades Cranianas/metabolismo , Hipocapnia/metabolismo , Masculino , Pressão Parcial , Ratos , Ratos Sprague-Dawley , Tálamo/irrigação sanguínea
13.
J Nucl Med ; 40(10): 1666-75, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10520707

RESUMO

UNLABELLED: As clinical PET becomes increasingly available, quantitative methods that are feasible in busy clinical settings are becoming necessary. We investigated the use of intracranial blood pools as sources of an input function for quantitative PET. METHODS: We studied 25 patients after the intravenous injection of [18F]6-fluoro-L-m-tyrosine and compared sampled blood time-activity curves with those obtained in small regions of interest (ROIs) defined in the blood pools visible in the PET images. Because of the comparatively large dimensions of the blood pool at the confluence of the superior sagittal, straight and transverse sinuses, a venous ROI input function was chosen for further analysis. We applied simple corrections to the ROI-derived time-activity curves, deriving expressions for partial volume, spillover and partition of tracer between plasma and red blood cells. The results of graphic and compartmental analysis using both sampled [Cs(t)] and ROI [Cr(t)] venous input functions for each patient were compared. We also used an analytic approach to examine possible differences between venous and arterial input functions in the cerebral circulation. RESULTS: Cr(t) peaked significantly earlier and higher than Cs(t) in this patient population, although the total integral under the curves did not differ significantly. We report some apparent differences in the results of modeling using the two input functions; however, neither the graphically determined influx constant, Ki, nor the model parameter that reflects presynaptic dopaminergic metabolism, k3, differed significantly between the two methods. The analytic results suggest that the venous ROI input function may be closer to the arterial supply of radiotracer to the brain than arterialized venous blood, at least in some patient populations. CONCLUSION: We present a simple method of obtaining an input function for PET that is applicable to a wide range of tracers and quantitative methods and is feasible for diagnostic PET imaging.


Assuntos
Circulação Cerebrovascular , Cavidades Cranianas/diagnóstico por imagem , Tomografia Computadorizada de Emissão/métodos , Cavidades Cranianas/anatomia & histologia , Cavidades Cranianas/metabolismo , Dopamina/metabolismo , Feminino , Radioisótopos de Flúor , Glucose/metabolismo , Humanos , Masculino , Matemática , Pessoa de Meia-Idade , Doses de Radiação , Compostos Radiofarmacêuticos , Tirosina/análogos & derivados , Tirosina/farmacocinética
14.
Neurosci Lett ; 266(3): 173-6, 1999 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-10465701

RESUMO

Primary neurovascular headaches, such as migraine and cluster headache probably involve activation of trigeminovascular pain structures projecting to the trigeminocervical complex of neurons in the caudal brain stem and upper cervical spinal cord. It has recently been demonstrated that blockade of the synthesis of nitric oxide (NO) by an NO synthesis inhibitor can abort acute migraine attacks and thus it is of interest to determine whether there is an influence of NO generation on trigeminocervical neurons. Cats were anaesthetised with alpha-chloralose (60 mg/kg, i.t.). supplemental 20 mg/kg, intravenously (i.v.)) and halothane for surgery (0.5-3% by inhalation). A circular midline craniotomy was performed to isolate the superior sagittal sinus (SSS) for electrical stimulation (0.3 Hz, 150 V, 250 micros duration for 2 h). Two groups were compared, one stimulated after administration of vehicle and the other stimulated after administration of N(G)-nitro-L-arginine methylester (L-NAME: 100 mg/kg, i.v.). After stimulation of the SSS Fos immunoreactivity was observed in lamina I/IIo of the trigeminal nucleus caudalis and dorsal horns of C1 and C2 to a median total of 136 cells (range 122-146). After L-NAME treatment Fos expression was significantly reduced to 40 cells (24-54; P < 0.02). In conclusion, inhibition of NO synthesis L-NAME markedly reduces Fos expression in the trigeminocervical complex of the cat. These data taken together with the clinical observations of the effect of NO synthesis blockade in migraine suggest a role for NO generation in mediating nociceptive transmission in acute migraine.


Assuntos
Cavidades Cranianas/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Neurônios/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/biossíntese , Medula Espinal/efeitos dos fármacos , Núcleos do Trigêmeo/efeitos dos fármacos , Animais , Gatos , Cavidades Cranianas/metabolismo , Estimulação Elétrica , Pescoço/inervação , Neurônios/metabolismo , Medula Espinal/citologia , Medula Espinal/metabolismo , Núcleos do Trigêmeo/citologia , Núcleos do Trigêmeo/metabolismo
15.
Pain ; 82(1): 15-22, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10422655

RESUMO

CP122,288, a conformationally restricted analogue of sumatriptan, is a highly potent inhibitor of neurogenic plasma protein extravasation (PPE) in rat and guinea pig at low doses where it has no 5HT1B-mediated vascular actions. We have examined its effect on a model of trigeminovascular nociception to assess the relative importance of vasoconstrictor and serotonin (5HT)(1B/1D) agonist activity to the modulation trigeminal neuronal activation. For comparison to activate relevant 5HT receptors, the clinically effective relatively lipophilic 5HT(1B/1D) agonist eletriptan was studied in parallel. The superior sagittal sinus was isolated in the alpha-chloralose (60 mg/kg, i.p. and 15-20 mg/kg i.v. supplement every 2 h) anaesthetized cat. Animals were prepared for stimulation and then maintained for 24 h before stimulation and perfusion for Fos immunohistochemistry. Stimulation of the superior sagittal sinus (250 micros, 100 V, 0.3 Hz) resulted in Fos expression in cells in the trigeminal nucleus caudalis and superficial laminae of the dorsal horns of C(1-2). Administration of low dose CP122,288 (100 ng/kg) had no effect on Fos expression after sinus stimulation either when administered alone or in combination with mannitol; the latter to ensure access to the trigeminocervical complex. The number of cells in the superficial laminae of the trigeminal nucleus caudalis with stimulation being a median of 50 (quartile range: 47-53) and 48 (35-48) after CP122,288, and after CP122,288 and mannitol 45 (41-53). In comparison, the clinically effective 5HT(1B/1D) agonist, eletriptan, reduced Fos expression in the trigeminocervical complex to a median of 24 (21-33). These data demonstrate that the potent inhibitor of neurogenic plasma protein extravasation (PPE) CP122,288 has no effect on Fos expression in central trigeminal neurons when administered at a dose which blocks PPE in rat and guinea pig, but has no vasoconstrictor 5HT(1B/1D) activity, and while ensuring its access to central trigeminal neurons. The data suggest that activation of the 5HT(1B/1D) receptor is important for the clinical action of this class of compounds and is consistent with the fact the CP122,288 is ineffective in the treatment of the acute attack of migraine.


Assuntos
Cavidades Cranianas/efeitos dos fármacos , Indóis/uso terapêutico , Proteínas Proto-Oncogênicas c-fos/biossíntese , Pirrolidinas/uso terapêutico , Agonistas do Receptor de Serotonina/uso terapêutico , Sumatriptana/análogos & derivados , Animais , Gatos , Cavidades Cranianas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Neurônios/efeitos dos fármacos , Estimulação Química , Sumatriptana/uso terapêutico , Neuralgia do Trigêmeo/tratamento farmacológico , Triptaminas , Vasoconstritores/uso terapêutico
16.
Brain Res ; 793(1-2): 297-301, 1998 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-9630685

RESUMO

To investigate immunological environment in the cerebrospinal fluid (CSF) system, ultrastructural and three-dimensional localization of intercellular adhesion molecule-1 (ICAM-1) was studied in the choroid plexus, arachnoid membrane and dural sinus of LPS-stimulated rats with immuno-SEM and TEM. The choroid plexus epithelial cells expressed rich ICAM-1 along the microvilli. The arachnoid trabeculae fibroblast-like cells demonstrated ICAM-1 expression on both sides facing the subarachnoid space moderately. The dural sinus endothelial cells, however, showed only few ICAM-1 expression and no specific localization. These results suggest that the choroid plexus and arachnoid membrane may play an important mutual role for leukocyte migration in the CSF system, and that the CSF system may function in immunoreaction independently of the vascular system with the aid of up-regulated ICAM-1 expression.


Assuntos
Aracnoide-Máter/metabolismo , Ventrículos Cerebrais/metabolismo , Plexo Corióideo/metabolismo , Cavidades Cranianas/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Lipopolissacarídeos/toxicidade , Animais , Aracnoide-Máter/patologia , Aracnoide-Máter/ultraestrutura , Ventrículos Cerebrais/patologia , Ventrículos Cerebrais/ultraestrutura , Plexo Corióideo/patologia , Plexo Corióideo/ultraestrutura , Cavidades Cranianas/patologia , Cavidades Cranianas/ultraestrutura , Feminino , Inflamação/metabolismo , Inflamação/patologia , Injeções Intraventriculares , Microscopia Eletrônica de Varredura , Microscopia Imunoeletrônica , Ratos , Ratos Endogâmicos Lew
17.
Am J Physiol ; 272(6 Pt 2): H2557-62, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9227531

RESUMO

In vitro data suggest that low tissue pH reduces, whereas extracellular alkalosis potentiates, cerebral anoxic injury via excitotoxic mechanisms. We tested the hypothesis that in vivo metabolic alkalemia potentiates defects in energy metabolism after global incomplete cerebral ischemia (12 min) and reperfusion (180 min) by an N-methyl-D-aspartate (NMDA) receptor-mediated mechanism. Brain ATP, phosphocreatine, and intracellular pH (pHi) were measured by 31P magnetic resonance spectroscopy in anesthetized dogs treated with 1) preischemic intravenous carbicarb buffer (NaHCO3+Na2CO3, Carb, n = 7); 2) carbicarb infusion plus NMDA receptor antagonist MK-801 (MK-801 + Carb, n = 7); 3) an osmotically equivalent volume of 5% NaCl (NaCl, n = 8); or 4) equivalent volume of 0.9% NaCl (Sal, n = 3). Sagittal sinus pH was raised to 7.82 +/- 0.04 before and 7.65 +/- 0.03 during ischemia in Carb vs. 7.72 +/- 0.01 and 7.60 +/- 0.01 in MK-801+Carb, 7.25 +/- 0.02 and 7.15 +/- 0.03 in NaCl, and 7.31 +/- 0.00 and 7.26 +/- 0.01 in Sal, respectively. Ischemic cerebral blood flow (CBF, radiolabeled microspheres), pHi, and ATP reduction were similar among groups. By 180 min of reperfusion, recovery of ATP was greater in MK-801+Carb (104 +/- 6% of baseline), NaCl (93 +/- 6%), and Sal (94 +/- 6%) than in Carb (47 +/- 6%). Intraischemic pHi was similar among groups, and pHi recovery did not vary among groups despite differences in sagittal sinus pH. In Carb, CBF was restored but with delayed hypoperfusion. We conclude that extracellular alkalosis is deleterious to postischemic CBF and energy metabolism, acting by NMDA receptor-mediated mechanisms.


Assuntos
Álcalis/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/fisiopatologia , Receptores de N-Metil-D-Aspartato/fisiologia , Trifosfato de Adenosina/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Encéfalo/metabolismo , Isquemia Encefálica/metabolismo , Carbonatos/farmacologia , Circulação Cerebrovascular/efeitos dos fármacos , Cavidades Cranianas/metabolismo , Maleato de Dizocilpina/farmacologia , Cães , Combinação de Medicamentos , Potenciais Somatossensoriais Evocados , Concentração de Íons de Hidrogênio , Masculino , Concentração Osmolar , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Reperfusão , Bicarbonato de Sódio/farmacologia , Cloreto de Sódio/farmacologia
18.
Stroke ; 27(7): 1241-8, 1996 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8685936

RESUMO

BACKGROUND AND PURPOSE: Administration of vasopressin during cardiopulmonary resuscitation (CPR) improves vital organ blood flow compared with epinephrine, but the effect of vasopressin on cerebral oxygenation and cerebral venous hypercarbia during CPR has not previously been studied. METHODS: Fourteen pigs were allocated to receive either epinephrine (0.2 mg/kg) or vasopressin (0.4 U/kg) after 4 minutes of ventricular fibrillation and 3 minutes of CPR. Cerebral blood flow was determined by radiolabeled microspheres, and arterial and cerebral venous blood gases were measured. RESULTS: Cerebral blood flow, measured before and 90 seconds and 5 minutes after drug administration, was 9 (3; 12), 25 (19; 27), and 18 (10; 23) mL/min per 100 g (median and 25th and 75th percentiles, respectively) in the epinephrine group and 12 (5; 16), 51 (48; 70), and 53 (45; 63) mL/min per 100 g in the vasopressin group (P<.05 at 90 seconds, P<.01 at 5 minutes between groups). Five minutes after drug administration, cerebral venous Pco2 was 63 (59; 68) mm Hg in the epinephrine group and 47 (43; 55) mm Hg in the vasopressin group (P<.01); at the same time cerebral venous pH was 7.18 (7.17; 7.20) and 7.26 (7.22; 7.36) (P<.01) in the epinephrine and vasopressin groups, respectively. Cerebral oxygen extraction ratio, calculated before and 90 seconds and 5 minutes after drug administration, was 0.42 (0.32; 0.57), 0.47 (0.41; 0.57), and 0.56 (0.56; 0.64) in the epinephrine group and 0.43 (0.38; 0.45), 0.38 (0.25; 0.44), and 0.35 (0.33; 0.49) in the vasopressin group (P<.05 at 90 seconds and 5 minutes). CONCLUSIONS: Compared with epinephrine, vasopressin not only increases cerebral blood flow but also improves cerebral oxygenation and decreases cerebral venous hypercarbia when administered during CPR in pigs.


Assuntos
Agonistas Adrenérgicos/uso terapêutico , Encéfalo/metabolismo , Reanimação Cardiopulmonar , Epinefrina/uso terapêutico , Consumo de Oxigênio , Vasoconstritores/uso terapêutico , Vasopressinas/uso terapêutico , Equilíbrio Ácido-Base , Animais , Dióxido de Carbono/sangue , Veias Cerebrais/efeitos dos fármacos , Ventrículos Cerebrais/irrigação sanguínea , Circulação Cerebrovascular , Cavidades Cranianas/metabolismo , Concentração de Íons de Hidrogênio , Hipercapnia/sangue , Hipercapnia/fisiopatologia , Oxigênio/sangue , Consumo de Oxigênio/efeitos dos fármacos , Suínos , Fibrilação Ventricular/terapia
19.
J Neuroimaging ; 6(2): 117-9, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8634485

RESUMO

A dynamic positron emission tomography (PET) study of the head was performed over 1 hour after the intravenous bolus administration of 18F-fluorodeoxyglucose (18F-FDG) to a 18-year-old patient with the clinical diagnosis of brain death. This dynamic PET study was performed on the seventh day after a severe posttraumatic closed-head injury. No intracerebral uptake or retention of tracer was noted, consistent with a diffuse absence of brain metabolism. A small amount of tracer was noted to slowly rise over time within the sagittal sinus, indicating that visualization of sagittal sinuses on technetium 99m-diethylene-triaminepentaacetic acid planar images could provide a falsely negative scintigraphic evaluation for the presence of brain death. It is concluded that PET FDG imaging may be a useful technique in evaluating patients for brain death.


Assuntos
Morte Encefálica/diagnóstico por imagem , Desoxiglucose/análogos & derivados , Radioisótopos de Flúor , Tomografia Computadorizada de Emissão , Adolescente , Encéfalo/metabolismo , Cavidades Cranianas/metabolismo , Desoxiglucose/administração & dosagem , Desoxiglucose/farmacocinética , Feminino , Radioisótopos de Flúor/administração & dosagem , Radioisótopos de Flúor/farmacocinética , Fluordesoxiglucose F18 , Traumatismos Cranianos Fechados/diagnóstico por imagem , Humanos , Injeções Intravenosas , Pentetato de Tecnécio Tc 99m/farmacocinética
20.
Vestn Khir Im I I Grek ; 155(3): 9-11, 1996.
Artigo em Russo | MEDLINE | ID: mdl-8966959

RESUMO

The local cerebral blood flow, oxygen tension, local impedance and intragastric pressure were examined in 13 patients with meningiomas of the middle third of the apical sagittal sinus at various stages of surgery including those after ablation of the intrasinus node and its reconstruction. In all the patients the decompressive cranial trepanation showed a blood stream enhancement but on the meningioma side. It is concluded that the degree of disturbances of oxygenative metabolism and blood circulation after the removal and reconstruction of the intrasinus node was dependent on the variant of the sinus injury.


Assuntos
Encéfalo/metabolismo , Circulação Cerebrovascular , Cavidades Cranianas/fisiopatologia , Neoplasias Meníngeas/fisiopatologia , Meningioma/fisiopatologia , Consumo de Oxigênio , Encéfalo/cirurgia , Cavidades Cranianas/metabolismo , Cavidades Cranianas/cirurgia , Humanos , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/cirurgia , Meningioma/metabolismo , Meningioma/cirurgia , Pressão Parcial
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