Monitoring cerebral oxygenation during balloon occlusion with multichannel NIRS

We report on oxygenation changes noninvasively recorded by multichannel continuous-wave near infrared spectroscopy (CW-NIRS) during endovascular neuroradiologic interventions requiring temporary balloon occlusion of arteries supplying the cerebral circulation. Digital subtraction angiography (DSA) provides reference data on the site, timing, and effectiveness of the flow stagnation as well as on the amount and direction of collateral circulation. This setting allows us to relate CW-NIRS findings to brain specific perfusion changes. We focused our analysis on the transition from normal perfusion to vessel occlusion, i.e., before hypoxia becomes clinically apparent. The localization of the maximal response correlated either with the core (occlusion of the middle cerebral artery) or with the watershed areas (occlusion of the internal carotid artery) of the respective vascular territories. In one patient with clinically and angiographically confirmed insufficient collateral flow during carotid artery occlusion, the total hemoglobin concentration became significantly asymmetric, with decreased values in the ipsilateral watershed area and contralaterally increased values. Multichannel CW-NIRS monitoring might serve as an objective and early predictive marker of critical perfusion changes during interventions-to prevent hypoxic damage of the brain. It also might provide valuable human reference data on oxygenation changes as they typically occur during acute stroke.

Protected stent retriever thrombectomy prevents iatrogenic emboli in new vascular territories

INTRODUCTION Diagnostic tools to show emboli reliably and protection techniques against embolization when employing stent retrievers are necessary to improve endovascular stroke therapy. The aim of the present study was to investigate iatrogenic emboli using susceptibility-weighted imaging (SWI) in an open series of patients who had been treated with stent retriever thrombectomy using emboli protection techniques. METHODS Patients with anterior circulation stroke examined with MRI before and after stent retriever thrombectomy were assessed for iatrogenic embolic events. Thrombectomy was performed in flow arrest and under aspiration using a balloon-mounted guiding catheter, a distal access catheter, or both. RESULTS In 13 of 57 patients (22.8 %) post-interventional SWI sequences detected 16 microemboli. Three of them were associated with small ischemic lesions on diffusion-weighted imaging (DWI). None of the microemboli were located in a new vascular territory, none showed clinical signs, and all 13 patients have been rated as Thrombolysis in Cerebral Infarction (TICI) 2b (n = 3) or 3 (n = 10). Retrospective reevaluation of the digital subtraction angiography (DSA) detected discrete flow stagnation nearby the iatrogenic microemboli in four patients with a positive persistent collateral sign in one. CONCLUSION Our study demonstrates two things: First, SWI seems to be more sensitive to detect emboli than DWI and DSA and, second, proximal or distal protected stent retriever thrombectomy seems to prevent iatrogenic embolization into new vascular territories during retraction of the thrombus, but not downstream during mobilization of the thrombus. Both techniques should be investigated and refined further.

COMPREENSÃO DO FUNCIONAMENTO MENTAL EM PACIENTES COM ACIDENTE CEREBROVASCULAR: UMA CONTRIBUIÇÃO DA PSICOLOGIA DA SAÚDE

O acidente cerebrovascular é uma doença de grande incidência no Brasil e no mundo. As pessoas que sofreram este tipo de acometimento podem apresentar seqüelas variadas, como motoras, cognitivas, sensoriais, sociais, afetivo-emocionais e transtornos psiquiátricos, levando a graus variados de dependência. Sendo assim, um estudo psicológico se faz importante, pois estas pessoas sofrerão mudanças em suas rotinas e no seu mundo interno.O presente trabalho trata-se de uma pesquisa clínico qualitativa, e teve como objetivos investigar as repercussões psicológicas de pacientes adultos que sofreram acidente cerebrovascular; compreender o funcionamento mental, a deterioração neuropsicológica e a adaptação humana desses pacientes, através da Escala de Avaliação Global do Funcionamento, do Desenho da Figura Humana, e da Escala do Diagnóstico Adaptativo Operacionalizado; compreender o sofrimento psicológico em narrativas da entrevista psicológica dessas pessoas e investigar como os indivíduos contam sua própria história numa compreensão psicossomática e psicanalítica. Para isso, utilizou-se o referencial teórico da Psicanálise e as concepções de Neuropsicanálise e Psicossomática. Foram analisados os relatos de cinco pacientes em tratamento num centro de reabilitação. Observou-se que por tratar-se de uma lesão cerebral, as repercussões psicológicas de quem sofreu acidente cerebrovascular devem ser observadas do ponto de vista neuropsicológico e a dinâmica afetivo-emocional. Os dados do Eixo V do DSM-IV, Escala de Avaliação Global do Funcionamento, e da Escala do Diagnóstico Adaptativo Operacionalizado de Ryad Simon apresentaram forte correlação estatística, embora a última seja mais compreensiva do ponto de vista psicanalítico; todos os pacientes apresentaram Adaptação Ineficaz. Quanto ao Desenho da Figura Humana, questionou-se a fidedignidade deste tipo de técnica nessa população, uma vez que os dados de organicidade interferem bastante. A história construída foi um instrumento importante para investigar como o indivíduo que sofreu acidente cerebrovascular contou sua própria história, seus mecanismos de defesa e as fantasias inconscientes, surgindo nesses relatos histórias importantes de depressão. Os mecanismos de defesa predominante no funcionamento mental desses pacientes foram a repressão e a desvalorização, no funcionamento neurótico, e a onipotência no funcionamento psicótico.(AU)

COMPREENSÃO DO FUNCIONAMENTO MENTAL EM PACIENTES COM ACIDENTE CEREBROVASCULAR: UMA CONTRIBUIÇÃO DA PSICOLOGIA DA SAÚDE

O acidente cerebrovascular é uma doença de grande incidência no Brasil e no mundo. As pessoas que sofreram este tipo de acometimento podem apresentar seqüelas variadas, como motoras, cognitivas, sensoriais, sociais, afetivo-emocionais e transtornos psiquiátricos, levando a graus variados de dependência. Sendo assim, um estudo psicológico se faz importante, pois estas pessoas sofrerão mudanças em suas rotinas e no seu mundo interno.O presente trabalho trata-se de uma pesquisa clínico qualitativa, e teve como objetivos investigar as repercussões psicológicas de pacientes adultos que sofreram acidente cerebrovascular; compreender o funcionamento mental, a deterioração neuropsicológica e a adaptação humana desses pacientes, através da Escala de Avaliação Global do Funcionamento, do Desenho da Figura Humana, e da Escala do Diagnóstico Adaptativo Operacionalizado; compreender o sofrimento psicológico em narrativas da entrevista psicológica dessas pessoas e investigar como os indivíduos contam sua própria história numa compreensão psicossomática e psicanalítica. Para isso, utilizou-se o referencial teórico da Psicanálise e as concepções de Neuropsicanálise e Psicossomática. Foram analisados os relatos de cinco pacientes em tratamento num centro de reabilitação. Observou-se que por tratar-se de uma lesão cerebral, as repercussões psicológicas de quem sofreu acidente cerebrovascular devem ser observadas do ponto de vista neuropsicológico e a dinâmica afetivo-emocional. Os dados do Eixo V do DSM-IV, Escala de Avaliação Global do Funcionamento, e da Escala do Diagnóstico Adaptativo Operacionalizado de Ryad Simon apresentaram forte correlação estatística, embora a última seja mais compreensiva do ponto de vista psicanalítico; todos os pacientes apresentaram Adaptação Ineficaz. Quanto ao Desenho da Figura Humana, questionou-se a fidedignidade deste tipo de técnica nessa população, uma vez que os dados de organicidade interferem bastante. A história construída foi um instrumento importante para investigar como o indivíduo que sofreu acidente cerebrovascular contou sua própria história, seus mecanismos de defesa e as fantasias inconscientes, surgindo nesses relatos histórias importantes de depressão. Os mecanismos de defesa predominante no funcionamento mental desses pacientes foram a repressão e a desvalorização, no funcionamento neurótico, e a onipotência no funcionamento psicótico.(AU)

Evidence for a protective role of metallothionein-1 in focal cerebral ischemia

Metallothioneins (MTs) are a family of metal binding proteins that have been proposed to participate in a cellular defense against zinc toxicity and free radicals. In the present study, we investigated whether increased expression of MT in MT-1 isoform-overexpressing transgenic mice (MT-TG) affords protection against mild focal cerebral ischemia and reperfusion. Transient focal ischemia was induced in control (wild type) and MT-TG mice by occluding the right middle cerebral artery for 45 min. Upon reperfusion, cerebral edema slowly developed and peaked at 24 hr as shown by T2-weighted MRI. The volume of affected tissue was on the average 42% smaller in MT-TG mice compared with control mice at 6, 9, 24, and 72 hr and 14 days postreperfusion (P < 0.01). In addition, functional studies showed that 3 weeks after reperfusion MT-TG mice showed a significantly better motor performance compared with control mice (P = 0.011). Although cortical baseline levels of MT-1 mRNA were similar in control and MT-TG mice, there was an increase in MT-1 mRNA levels in the ischemic cortex of MT-TG mice to 7.5 times baseline levels compared with an increase to 2.3 times baseline levels in control mice 24 hr after reperfusion. In addition, MT-TG mice showed an increased MT immunoreactivity in astrocytes, vascular endothelial cells, and neurons 24 hr after reperfusion whereas in control mice MT immunoreactivity was restricted mainly to astrocytes and decreased in the infarcted tissue. These results provide evidence that increased expression of MT-1 protects against focal cerebral ischemia and reperfusion.

Effects of in vivo adventitial expression of recombinant endothelial nitric oxide synthase gene in cerebral arteries

Nitric oxide (NO), synthesized from l-arginine by NO synthases (NOS), plays an essential role in the regulation of cerebrovascular tone. Adenoviral vectors have been widely used to transfer recombinant genes to different vascular beds. To determine whether the recombinant endothelial NOS (eNOS) gene can be delivered in vivo to the adventitia of cerebral arteries and functionally expressed, a replication-incompetent adenoviral vector encoding eNOS gene (AdCMVNOS) or β-galactosidase reporter gene (AdCMVLacZ) was injected into canine cerebrospinal fluid (CSF) via the cisterna magna (final viral titer in CSF, 109 pfu/ml). Adventitial transgene expression was demonstrated 24 h later by β-galactosidase histochemistry and quantification, eNOS immunohistochemistry, and Western blot analysis of recombinant eNOS. Electron microscopy immunogold labeling indicated that recombinant eNOS protein was expressed in adventitial fibroblasts. In AdCMVNOS-transduced arteries, basal cGMP production and bradykinin-induced relaxations were significantly augmented when compared with AdCMVLacZ-transduced vessels (P < 0.05). The increased receptor-mediated relaxations and cGMP production were inhibited by eNOS inhibitors. In addition, the increase in cGMP production was reversed in the absence of calcium, suggesting that the increased NO production did not result from inducible NOS expression. The present study demonstrates the successful in vivo transfer and functional expression of recombinant eNOS gene in large cerebral arteries. It also suggests that perivascular eNOS gene delivery via the CSF is a feasible approach that does not require interruption of cerebral blood flow.

Vascular imprints of neuronal activity: Relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation

Modern functional neuroimaging methods, such as positron-emission tomography (PET), optical imaging of intrinsic signals, and functional MRI (fMRI) utilize activity-dependent hemodynamic changes to obtain indirect maps of the evoked electrical activity in the brain. Whereas PET and flow-sensitive MRI map cerebral blood flow (CBF) changes, optical imaging and blood oxygenation level-dependent MRI map areas with changes in the concentration of deoxygenated hemoglobin (HbR). However, the relationship between CBF and HbR during functional activation has never been tested experimentally. Therefore, we investigated this relationship by using imaging spectroscopy and laser-Doppler flowmetry techniques, simultaneously, in the visual cortex of anesthetized cats during sensory stimulation. We found that the earliest microcirculatory change was indeed an increase in HbR, whereas the CBF increase lagged by more than a second after the increase in HbR. The increased HbR was accompanied by a simultaneous increase in total hemoglobin concentration (Hbt), presumably reflecting an early blood volume increase. We found that the CBF changes lagged after Hbt changes by 1 to 2 sec throughout the response. These results support the notion of active neurovascular regulation of blood volume in the capillary bed and the existence of a delayed, passive process of capillary filling.

Vascular endothelial growth factor: Direct neuroprotective effect in in vitro ischemia

Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic peptide with recently identified neurotrophic effects. Because some neurotrophic factors can protect neurons from hypoxic or ischemic injury, we investigated the possibility that VEGF has similar neuroprotective properties. In HN33, an immortalized hippocampal neuronal cell line, VEGF reduced cell death associated with an in vitro model of cerebral ischemia: at a maximally effective concentration of 50 ng/ml, VEGF approximately doubled the number of cells surviving after 24 h of hypoxia and glucose deprivation. To investigate the mechanism of neuroprotection by VEGF, the expression of known target receptors for VEGF was measured by Western blotting, which showed that HN33 cells expressed VEGFR-2 receptors and neuropilin-1, but not VEGFR-1 receptors. The neuropilin-1 ligand placenta growth factor-2 failed to reproduce the protective effect of VEGF, pointing to VEGFR-2 as the site of VEGF's neuroprotective action. Two phosphatidylinositol 3′-kinase inhibitors, wortmannin and LY294002, reversed the neuroprotective effect of VEGF, implicating the phosphatidylinositol 3′-kinase/Akt signal transduction system in VEGF-mediated neuroprotection. VEGF also protected primary cultures of rat cerebral cortical neurons from hypoxia and glucose deprivation. We conclude that in addition to its known role as an angiogenic factor, VEGF may exert a direct neuroprotective effect in hypoxic-ischemic injury.

EphA4 regulates central nervous system vascular formation

Molecules involved in axon guidance have recently also been shown to play a role in blood vessel guidance. To examine whether axon guidance molecules, such as the EphA4 receptor tyrosine kinase, might also play a role in development of the central nervous system (CNS) vasculature and repair following CNS injury, we examined wild-type and EphA4 null mutant (-/-) mice. EphA4-/- mice exhibited an abnormal CNS vascular structure in both the cerebral cortex and the spinal cord, with disorganized branching and a 30% smaller diameter. During development, EphA4 was expressed on endothelial cells. This pattern of expression was not maintained in the adult. After spinal cord injury in wild-type mice, expression of EphA4 was markedly up-regulated on activated astrocytes, many of which were tightly associated with blood vessels. In EphA4-/- spinal cord following injury, astrocytes were not as tightly associated with blood vessels as the wild-type astrocytes. In uninjured EphA4-/- mice, the blood-brain barrier (BBB) appeared normal, but it showed prolonged leakage following spinal cord injury. These results support a role for EphA4 in CNS vascular formation and guidance during development and an additional role in BBB repair.

COMPREENSÃO DO FUNCIONAMENTO MENTAL EM PACIENTES COM ACIDENTE CEREBROVASCULAR: UMA CONTRIBUIÇÃO DA PSICOLOGIA DA SAÚDE

O acidente cerebrovascular é uma doença de grande incidência no Brasil e no mundo. As pessoas que sofreram este tipo de acometimento podem apresentar seqüelas variadas, como motoras, cognitivas, sensoriais, sociais, afetivo-emocionais e transtornos psiquiátricos, levando a graus variados de dependência. Sendo assim, um estudo psicológico se faz importante, pois estas pessoas sofrerão mudanças em suas rotinas e no seu mundo interno.O presente trabalho trata-se de uma pesquisa clínico qualitativa, e teve como objetivos investigar as repercussões psicológicas de pacientes adultos que sofreram acidente cerebrovascular; compreender o funcionamento mental, a deterioração neuropsicológica e a adaptação humana desses pacientes, através da Escala de Avaliação Global do Funcionamento, do Desenho da Figura Humana, e da Escala do Diagnóstico Adaptativo Operacionalizado; compreender o sofrimento psicológico em narrativas da entrevista psicológica dessas pessoas e investigar como os indivíduos contam sua própria história numa compreensão psicossomática e psicanalítica. Para isso, utilizou-se o referencial teórico da Psicanálise e as concepções de Neuropsicanálise e Psicossomática. Foram analisados os relatos de cinco pacientes em tratamento num centro de reabilitação. Observou-se que por tratar-se de uma lesão cerebral, as repercussões psicológicas de quem sofreu acidente cerebrovascular devem ser observadas do ponto de vista neuropsicológico e a dinâmica afetivo-emocional. Os dados do Eixo V do DSM-IV, Escala de Avaliação Global do Funcionamento, e da Escala do Diagnóstico Adaptativo Operacionalizado de Ryad Simon apresentaram forte correlação estatística, embora a última seja mais compreensiva do ponto de vista psicanalítico; todos os pacientes apresentaram Adaptação Ineficaz. Quanto ao Desenho da Figura Humana, questionou-se a fidedignidade deste tipo de técnica nessa população, uma vez que os dados de organicidade interferem bastante. A história construída foi um instrumento importante para investigar como o indivíduo que sofreu acidente cerebrovascular contou sua própria história, seus mecanismos de defesa e as fantasias inconscientes, surgindo nesses relatos histórias importantes de depressão. Os mecanismos de defesa predominante no funcionamento mental desses pacientes foram a repressão e a desvalorização, no funcionamento neurótico, e a onipotência no funcionamento psicótico.(AU)

Retinal vascular dysfunction relates to cognitive impairment in Alzheimer's disease

Cerebral vascular dysregulation has been increasingly implicated as a risk factor in the development of Alzheimer disease (AD)1; however, because of the difficulties associated with assessing and visualizing the cerebral vasculature directly, the ability to detect such dysregulation, noninvasively, is currently limited.2 Consequently, one concept that is being increasingly explored is the possibility of using the eye as a "window to the brain"; this approach has reasonable scientific validity as the retinal and brain vessels share a large number of embryological, anatomic, and functional similarities.2 Indeed, previous research has demonstrated a correlation between cognition and the geometry of the retinal vessels in elderly people.3 The aim of this pilot study, therefore, was to explore whether microvascular functional anomalies are evident at the retinal level in mild AD patients and to determine whether these anomalies relate to the degree of concurrent cognitive deficit..

Role of Vascular Smooth Muscle Cell PiT-2 in Basal Ganglia Calcification

Thesis (Master's)--University of Washington, 2016-08

Infarto Cerebral del territorio Vértebro-Basilar: Comunicación de una serie de pacientes asistidos en el Hospital de Clínicas de Montevideo

Introducción: El ataque cerebro vascular tiene una elevada incidencia y mortalidad en Uruguay representando, aquellos de la circulación posterior, un porcentaje importante de ellos. En este estudio describimos características basales, clínicas, diagnósticas y terapéuticas de una serie de pacientes con ataque cerebro vascular de la circulación posterior. Material y métodos: Estudio observacional descriptivo. Inclusión: pacientes con diagnóstico de ataque cerebro vascular de la circulación posterior atendidos en el Hospital de Clínicas entre junio de 2007 y 2014. Resultados: Se incluyeron 140 pacientes con una edad media de 68 años y elevada frecuencia de factores de riesgo clásicos para enfermedad cerebro vascular. Predominó la clínica cerebelosa y piramidal, con un puntaje medio bajo en la escala de NIHSS (5,2) y una baja sensibilidad de la Tomografía de cráneo para el diagnóstico. La etiología determinada más prevalente fue la cardioembolia. Un quinto de los pacientes consultó antes de las 4,5 horas y el 3,8% de los pacientes fue tratado con trombolisis iv. Discusión y comentarios: Se trata de la mayor serie de ataque cerebro vascular de la circulación posterior reportada en nuestro país, la forma de presentación fue similar a la descrita en la literatura. La escala de NIHSS infravaloró la severidad de este tipo de ataque cerebro vascular. La tomografia de cráneo tuvo baja sensibilidad diagnóstica y el porcentaje de resonancias magnéticas realizadas fue bajo. Un bajo número de pacientes consultó en ventana para trombolisis iv y solo al 3,8% de los casos se le realizó dicho tratamiento.

Flujo sanguíneo cerebral durante el ejercicio de esprint

Se desconocen los efectos del entrenamiento interválico de alta intesidad (HIIT) sobre el flujo sanguíneo cerebral (FSC) y la oxigenación cerebral. Por ello reclutamos a 20 voluntarios que realizaron una sesión de HIIT (4 test de Wingate con recuperaciones de 4 minutos). Se midió la oxigenación del lóbulo frontal (OLF) y el Vastus lateralis (VL) a través de espectrofotometría cercana a los infrarrojos (NIRS). También se registró la velocidad de la sangre en las arterias cerebrales medias (vACM) mediante Doppler. La vACM disminuyó entre un 5 y 10 % en el primer esprint. En los siguientes esprints se redujo aún más. La vACM descendió en cada esprint coincidiendo con la disminución de la presión tele-espiratoria de dióxido de carbono (PETCO2) y con valores superiores de ventilación pulmonar (VE). Al interrumpirse el pedaleo se redujo bruscamente la vACM. Sin embargo, la OLF se mantuvo estable en el primer esprint sólo reduciéndose ligeramente durante el segundo y tercer Wingate (el cuarto fue similar al tercero). Este estudio muestra que la vACM disminuye durante los ejercicios de esprint, posiblemente debido a la hipocapnia. La reducción de la vACM no ejerce efectos funcionales ni relevantes sobre la oxigenación cerebral, gracias al ajuste de la conductancia vascular a través de los mecanismos de autoregulación, sin que parezca afectar negativamente al rendimiento.

Vascular Pattern In Enchondroma And Chondrosarcoma: Clinical And Immunohistologic Study.

Although cartilaginous tumors have low microvascular density, vessels are important for the provision of nutrition so that the tumor can grow and generate metastasis. The aim of this study was to assess the value of the vascular pattern classification as a prognostic tool in chondrosarcomas (CSs) and its relation with vascular endothelial growth factor (VEGF) expression. This was a retrospective study of 21 enchondromas and 57 conventional CSs. Clinical data and outcome were retrieved from medical files. CSs histologic grades (on a scale of 1 to 3) were determined according to the World Health Organization classification. The vascular pattern (on a scale of A to C) was assessed through CD34, according to Kalinski. CD105 and VEGF were also evaluated. Poor outcome was significantly associated with vascular pattern groups B and C. Higher vascular pattern were 6.5 times more frequent in moderate-grade and high-grade CSs than in grade 1 CS. On multivariate analysis, a clear correlation was found between VEGF overexpression and B/C vascular patterns. Only 18 (benign and malignant) tumors stained for CD105. The results point to the use of the vascular pattern classification as a prognostic tool in CSs and to differentiate low-grade from moderate-grade/high-grade CSs. Vascular pattern might be also used to complement histologic grade, VEGF immunostaining, and microvascular density, for indicating a patient's prognosis. Low-grade CSs develop under low neoangiogenesis, which conforms to the slow growth rate of these tumors.