RESUMEN
OBJECTIVE: Cognitive impairments in type 1 diabetes may result from hyperglycemia-associated cerebral microangiopathy. We aimed to identify cerebral microangiopathy and skin microvascular dysfunction-as a surrogate marker for generalized microvascular function-as predictors of cognitive performance over time. METHODS: In this prospective cohort study, 25 type 1 diabetes patients with proliferative retinopathy and 25 matched healthy controls underwent neurocognitive testing at baseline and after follow-up (3.8 ± 0.8 years). At baseline, 1.5-T cerebral magnetic resonance imaging was used to detect WML and cerebral microbleeds. Skin capillary perfusion was assessed by means of capillary microscopy. RESULTS: In type 1 diabetes patients, but not in healthy controls, the presence of WML (ß = -0.419; P = 0.037) as well as lower skin capillary perfusion (baseline: ß = 0.753; P < 0.001; peak hyperemia: ß = 0.743; P = 0.001; venous occlusion: ß = 0.675; P = 0.003; capillary recruitment: ß = 0.549; P = 0.022) at baseline was associated with lower cognitive performance over time, independent of age, sex, HbA1c, and severe hypoglycemia. The relationship between WML and lower cognitive performance was significantly reduced after adjusting for capillary perfusion. CONCLUSIONS: These data fit the hypothesis that cerebral microangiopathy is a manifestation of generalized microvascular dysfunction, leading to lower cognitive performance.
Asunto(s)
Capilares , Corteza Cerebelosa , Trastornos Cerebrovasculares , Cognición , Diabetes Mellitus Tipo 1 , Imagen por Resonancia Magnética , Microcirculación , Piel , Sustancia Blanca , Adulto , Capilares/diagnóstico por imagen , Capilares/fisiopatología , Corteza Cerebelosa/irrigación sanguínea , Corteza Cerebelosa/diagnóstico por imagen , Corteza Cerebelosa/fisiopatología , Trastornos Cerebrovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/fisiopatología , Diabetes Mellitus Tipo 1/diagnóstico por imagen , Diabetes Mellitus Tipo 1/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Piel/irrigación sanguínea , Piel/diagnóstico por imagen , Sustancia Blanca/irrigación sanguínea , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/fisiopatologíaRESUMEN
Electrical synapses formed by connexin36 (Cx36)-containing gap junctions between interneurons in the cerebellar cortex have been well characterized, including those formed between basket cells and between Golgi cells, and there is gene reporter-based evidence for the expression of connexin45 (Cx45) in the cerebellar molecular layer. Here, we used immunofluorescence approaches to further investigate expression patterns of Cx36 and Cx45 in this layer and to examine localization relationships of these connexins with each other and with glial connexin43 (Cx43). In mice, strain differences were found, such that punctate labelling for Cx36 was differentially distributed in the molecular layer of C57BL/6 vs. CD1 mice. In mice with EGFP reporter representing Cx36 expression, Cx36-puncta were localized to processes of stellate cells and other cerebellar interneurons. Punctate labelling of Cx45 was faint in the molecular layer of wild-type mice and was increased in intensity in mice with Cx36 gene ablation. The vast majority of Cx36-puncta co-localized with Cx45-puncta, which in turn was associated with the scaffolding protein zonula occludens-1. In rats, Cx45-puncta were also co-localized with Cx36-puncta and additionally occurred along Bergmann glial processes adjacent to Cx43-puncta. The results indicate strain and species differences in Cx36 as well as Cx45 expression, possible compensatory processes after loss of Cx36 expression and localization of Cx45 to both neuronal and Bergmann glial gap junctions. Further, expression of both Cx43 and Cx45 in Bergmann glia of rat may contribute to the complex properties of junctional coupling between these cells and perhaps to their reported coupling with Purkinje cells.
Asunto(s)
Corteza Cerebelosa/metabolismo , Conexina 43/metabolismo , Conexinas/metabolismo , Neuroglía/metabolismo , Neuronas/metabolismo , Animales , Vasos Sanguíneos/citología , Vasos Sanguíneos/metabolismo , Corteza Cerebelosa/irrigación sanguínea , Corteza Cerebelosa/citología , Conexinas/genética , Técnica del Anticuerpo Fluorescente , Uniones Comunicantes/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Masculino , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Neuroglía/citología , Neuronas/citología , Ratas Sprague-Dawley , Especificidad de la Especie , Proteína delta-6 de Union ComunicanteRESUMEN
The relationship between peri-infarct depolarizations (PIDs) and infarction was investigated in a model of preconditioning by cortical freeze lesions (cryogenic lesions, CL) in the Spontaneously Hypertensive Rat. Small (< 5 mm(3)) lesions produced 24 hours before permanent focal ischemia were protective, without impacting baseline cerebral blood flow (CBF) and metabolism. Prior CL reduced infarct volume, associated with improved penumbral CBF as previously showed for ischemic preconditioning. The brief initial procedure avoided sham effects on infarct volume after subsequent occlusion under brief anesthesia. However, under prolonged isoflurane anesthesia for perfusion monitoring both sham and CL rats showed reduced PID incidence relative to naive animals. This anesthesia effect could be eliminated by using α-chloralose during perfusion imaging. As an additional methodological concern, blood glucose was frequently elevated at the time of the second surgery, reflecting buprenorphine-induced pica and other undefined mechanisms. Even modest hyperglycemia (>10 mmol/L) reduced PID incidence. In normoglycemic animals CL preconditioning reduced PID number by 50%, demonstrating associated effects on PID incidence, penumbral perfusion, and infarct progression. Hyperglycemia suppressed PIDs without affecting the relationship between CBF and infarction. This suggests that the primary effect of preconditioning is to improve penumbral perfusion, which in turn impacts PID incidence and infarct size.
Asunto(s)
Corteza Cerebelosa/patología , Infarto Cerebral/complicaciones , Infarto Cerebral/patología , Circulación Cerebrovascular , Depresión de Propagación Cortical , Congelación , Hiperglucemia/complicaciones , Anestesia , Anestésicos por Inhalación/uso terapéutico , Anestésicos Intravenosos/uso terapéutico , Animales , Corteza Cerebelosa/irrigación sanguínea , Corteza Cerebelosa/fisiopatología , Infarto Cerebral/etiología , Infarto Cerebral/fisiopatología , Cloralosa/uso terapéutico , Modelos Animales de Enfermedad , Precondicionamiento Isquémico , Isoflurano/uso terapéutico , Masculino , Ratas Endogámicas SHRRESUMEN
Cerebral autoregulation (CA) is the mechanism that allows the brain to maintain a stable blood flow despite changes in blood pressure. Dynamic CA can be quantified based on continuous measurements of systemic mean arterial pressure (MAP) and global cerebral blood flow. Here, we show that dynamic CA can be quantified also from local measurements that are sensitive to the microvasculature. We used near-infrared spectroscopy (NIRS) to measure temporal changes in oxy- and deoxy-hemoglobin concentrations in the prefrontal cortex of 11 human subjects. A novel hemodynamic model translates those changes into changes of cerebral blood volume and blood flow. The interplay between them is described by transfer function analysis, specifically by a high-pass filter whose cutoff frequency describes the autoregulation efficiency. We have used pneumatic thigh cuffs to induce MAP perturbation by a fast release during rest and during hyperventilation, which is known to enhance autoregulation. Based on our model, we found that the autoregulation cutoff frequency increased during hyperventilation in comparison to normal breathing in 10 out of 11 subjects, indicating a greater autoregulation efficiency. We have shown that autoregulation can reliably be measured noninvasively in the microvasculature, opening up the possibility of localized CA monitoring with NIRS.
Asunto(s)
Corteza Cerebelosa/irrigación sanguínea , Corteza Cerebelosa/química , Circulación Cerebrovascular , Hemoglobinas/análisis , Microvasos/fisiología , Oxihemoglobinas/análisis , Espectroscopía Infrarroja Corta/métodos , Adulto , Corteza Cerebelosa/fisiología , Simulación por Computador , Femenino , Hemodinámica , Hemoglobinas/metabolismo , Homeostasis , Humanos , Masculino , Microvasos/química , Persona de Mediana Edad , Modelos Biológicos , Imagen Óptica/métodos , Oxihemoglobinas/metabolismo , Adulto JovenRESUMEN
The molecular pathways underlying the pathogenesis after subarachnoid haemorrhage (SAH) are poorly understood and continue to be a matter of debate. A valid murine SAH injection model is not yet available but would be the prerequisite for further transgenic studies assessing the mechanisms following SAH. Using the murine single injection model, we examined the effects of SAH on regional cerebral blood flow (rCBF) in the somatosensory (S1) and cerebellar cortex, neuro-behavioural and morphological integrity and changes in quantitative electrocorticographic and electrocardiographic parameters. Micro CT imaging verified successful blood delivery into the cisterna magna. An acute impairment of rCBF was observed immediately after injection in the SAH and after 6, 12 and 24 hours in the S1 and 6 and 12 hours after SAH in the cerebellum. Injection of blood into the foramen magnum reduced telemetric recorded total ECoG power by an average of 65%. Spectral analysis of ECoGs revealed significantly increased absolute delta power, i.e., slowing, cortical depolarisations and changes in ripples and fast ripple oscillations 12 hours and 24 hours after SAH. Therefore, murine single-blood-injection SAH model is suitable for pathophysiological and further molecular analysis following SAH.
Asunto(s)
Corteza Cerebelosa/irrigación sanguínea , Modelos Animales de Enfermedad , Ratones , Corteza Somatosensorial/irrigación sanguínea , Hemorragia Subaracnoidea/fisiopatología , Animales , Corteza Cerebelosa/fisiopatología , Cisterna Magna , Masculino , Flujo Sanguíneo Regional , Corteza Somatosensorial/fisiopatologíaRESUMEN
Glutamate transporters (excitatory amino-acid transporters (EAATs)) are essential for brain homeostasis. While previous studies indicate that the vascular endothelium contributes to glutamate efflux in the adult brain, little information is available regarding glutamate uptake in the immature brain. The present study shows a differential expression pattern of EAATs between cortical microvessels in adults and newborns. In addition, adult cortical endothelial cells take up glutamate more efficiently than neonatal cells. Our findings indicate age-specific changes in extracellular glutamate regulation by brain endothelial cells, suggesting differences in the efficiency of glutamate efflux during an excitotoxic process that, in turn, may contribute to age-specific brain vulnerability.
Asunto(s)
Sistema de Transporte de Aminoácidos X-AG/genética , Corteza Cerebelosa/irrigación sanguínea , Corteza Cerebelosa/crecimiento & desarrollo , Células Endoteliales/metabolismo , Ácido Glutámico/metabolismo , Sistema de Transporte de Aminoácidos X-AG/análisis , Sistema de Transporte de Aminoácidos X-AG/metabolismo , Animales , Células Cultivadas , Corteza Cerebelosa/citología , Corteza Cerebelosa/metabolismo , Células Endoteliales/citología , Regulación del Desarrollo de la Expresión Génica , RatonesRESUMEN
Activation of astrocytic metabotropic glutamate receptor 5 (mGluR5) is postulated to elicit calcium transients, triggering a chain of events that ultimately regulates cerebral blood flow by changing the tone of smooth muscle cells of nearby arterioles. Using concurrent in vivo optical imaging and determination of receptor occupancy with (11)C-ABP688, we report here that blocking â¼80% of mGluR5 in vivo does not affect transient hemodynamic responses on brief whisker stimulations while transiently reducing neuronal activity as measured by voltage-sensitive dye imaging. Our results show that mechanisms other than activation of mGluR5 are required to trigger the initial hemodynamic response in normal physiological conditions.
Asunto(s)
Corteza Cerebelosa/irrigación sanguínea , Hemodinámica , Receptores de Glutamato Metabotrópico/metabolismo , Animales , Corteza Cerebelosa/citología , Corteza Cerebelosa/metabolismo , Masculino , Neuronas/citología , Neuronas/metabolismo , Ratas , Ratas Sprague-Dawley , Receptor del Glutamato Metabotropico 5 , Receptores de Glutamato Metabotrópico/antagonistas & inhibidoresRESUMEN
One contention within the field of neuroimaging concerns the character of the depicted activity: Does it represent neuronal action potential generation (i.e., spiking) or postsynaptic excitation? This question is related to the metabolic costs of different aspects of neurosignaling. The cerebellar cortex is well suited for addressing this problem because synaptic input to and spiking of the principal cell, the Purkinje cell (PC), are spatially segregated. Also, PCs are pacemakers, able to generate spikes endogenously. We examined the contributions to cerebellar cortical oxygen consumption (CMRO2) of postsynaptic excitation and PC spiking during evoked and ongoing neuronal activity in the rat. By inhibiting excitatory synaptic input using ionotropic glutamate receptor blockers, we found that the increase in CMRO2 evoked by parallel fiber (PF) stimulation depended entirely on postsynaptic excitation. In contrast, PC spiking was largely responsible for the increase in CMRO2 when ongoing neuronal activity was increased by gamma-aminobutyric acid type A receptor blockade. In this case, CMRO2 increased equally during PC spiking with excitatory synaptic activity as during PC pacemaker spiking without excitatory synaptic input. Subsequent inhibition of action potential propagation and neurotransmission by blocking voltage-gated Na+-channels eliminated the increases in CMRO2 due to PF stimulation and increased PC spiking, but left a large fraction of CMRO2, i.e., basal CMRO2, intact. In conclusion, whereas basal CMRO2 in anesthetized animals did not seem to be related to neurosignaling, increases in CMRO2 could be induced by all aspects of neurosignaling. Our findings imply that CMRO2 responses cannot a priori be assigned to specific neuronal activities.
Asunto(s)
Potenciales de Acción/fisiología , Corteza Cerebelosa/citología , Potenciales Postsinápticos Excitadores/fisiología , Consumo de Oxígeno/fisiología , Células de Purkinje/fisiología , 6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , Análisis de Varianza , Animales , Bicuculina/farmacología , Biofisica , Isótopos de Carbono/metabolismo , Corteza Cerebelosa/irrigación sanguínea , Desoxiglucosa/metabolismo , Maleato de Dizocilpina/farmacología , Estimulación Eléctrica/métodos , Antagonistas de Aminoácidos Excitadores/farmacología , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Antagonistas del GABA/farmacología , Flujometría por Láser-Doppler/métodos , Masculino , Fibras Nerviosas/fisiología , Vías Nerviosas/fisiología , Consumo de Oxígeno/efectos de los fármacos , Ratas , Ratas Wistar , Flujo Sanguíneo Regional/efectos de los fármacos , Bloqueadores de los Canales de Sodio/farmacología , Tetrodotoxina/farmacologíaRESUMEN
Adenosine, astrocyte metabotropic glutamate receptors (mGluRs), and epoxyeicosatrienoic acids (EETs) have been implicated in neurovascular coupling. Although A(2A) and A(2B) receptors mediate cerebral vasodilation to adenosine, the role of each receptor in the cerebral blood flow (CBF) response to neural activation remains to be fully elucidated. In addition, adenosine can amplify astrocyte calcium, which may increase arachidonic acid metabolites such as EETs. The interaction of these pathways was investigated by determining if combined treatment with antagonists exerted an additive inhibitory effect on the CBF response. During whisker stimulation of anesthetized rats, the increase in cortical CBF was reduced by approximately half after individual administration of A(2B), mGluR and EET antagonists and EET synthesis inhibitors. Combining treatment of either a mGluR antagonist, an EET antagonist, or an EET synthesis inhibitor with an A(2B) receptor antagonist did not produce an additional decrement in the CBF response. Likewise, the CBF response also remained reduced by approximately 50% when an EET antagonist was combined with an mGluR antagonist or an mGluR antagonist plus an A(2B) receptor antagonist. In contrast, A(2A) and A(3) receptor antagonists had no effect on the CBF response to whisker stimulation. We conclude that (1) adenosine A(2B) receptors, rather than A(2A) or A(3) receptors, play a significant role in coupling cortical CBF to neuronal activity, and (2) the adenosine A(2B) receptor, mGluR, and EETs signaling pathways are not functionally additive, consistent with the possibility of astrocytic mGluR and adenosine A(2B) receptor linkage to the synthesis and release of vasodilatory EETs.
Asunto(s)
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Ácido 8,11,14-Eicosatrienoico/metabolismo , Ácidos Araquidónicos/metabolismo , Corteza Cerebelosa/irrigación sanguínea , Unión Neuroefectora/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Receptores Purinérgicos P1/metabolismo , Vasodilatación/fisiología , Vasodilatadores/metabolismo , Vibrisas , Animales , Corteza Cerebelosa/metabolismo , Circulación Cerebrovascular/efectos de los fármacos , Circulación Cerebrovascular/fisiología , Masculino , Antagonistas de Receptores Purinérgicos P1 , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Vasodilatación/efectos de los fármacosRESUMEN
The study of brain histological specimens from patients with Creutzfeldt-Jakob disease (CJD) revealed the active reproduction and accumulation of pathological prions in the epitheliocytes of cerebral vascular brain plexuses in a new variant of CJD. There was PrPCD accumulation on the cerebral ventricular ependymal cells and in the subpial superficial cortex parts of the cerebellum and brain to give rise to diffuse clusters, immature and kuru-plaques. Morphological changes in the blood-cerebrospinal fluid and cerebrospinal fluid-brain barriers are described and the possible pathways of intracerebral distribution of prions with cerebrospinal fluid considered.
Asunto(s)
Corteza Cerebelosa/metabolismo , Corteza Cerebelosa/patología , Síndrome de Creutzfeldt-Jakob/metabolismo , Síndrome de Creutzfeldt-Jakob/patología , Proteínas PrPSc/metabolismo , Corteza Cerebelosa/irrigación sanguínea , Epéndimo/metabolismo , Epéndimo/patología , Células Epitelioides/metabolismo , Células Epitelioides/patología , Femenino , Humanos , MasculinoRESUMEN
Given the high burden of atherosclerotic cardiovascular disease in dialysis patients, we hypothesized that cognitive testing would reveal subtle abnormalities in subcortical brain function, a measure frequently associated with cerebrovascular disease. Detailed neurocognitive testing was performed in 25 hemodialysis patients. All patients had Mini-Mental State Examination (MMSE) scores >24 and had no history of cerebrovascular disease. Where appropriate, scores were normalized for age, gender, and education. One-sample t tests were used to compare differences in cognitive function between dialysis patients and normative data. The mean age was 57 years, and the mean MMSE was 27.5. Fourteen subjects (56%) were females, and 15 white (60%). Results of the North American Adult Reading Test, a measure of verbal intelligence, were comparable with the general population. Similarly, measures of cortical function, namely retention and recognition scores from the Word List Learning subtest of the Wechsler Memory Scale-III, were preserved when compared with normative data where reference = 10. Significant deficits were seen on tests assessing subcortical function: scores (mean+/-standard deviation) for block design, and symbol coding subtests of the Wechsler Adult Intelligence Scale-III were 7.0+/-1.7 and 7.7+/-3.1, respectively (p<0.001 for both comparisons with normative data). Similarly, adjusted scores on the trails A and B tests were 40.5+/-8.3 and 41.8+/-11.3, respectively (p<0.001 for both comparisons with normative data where reference= 50). These results suggest that, despite relatively normal MMSE scores, mild cognitive impairment may be prevalent in hemodialysis patients. The pattern of cognitive dysfunction is primarily subcortical in nature.
Asunto(s)
Trastornos del Conocimiento , Arteriosclerosis Intracraneal , Diálisis Renal , Adulto , Anciano , Anciano de 80 o más Años , Corteza Cerebelosa/irrigación sanguínea , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Femenino , Humanos , Arteriosclerosis Intracraneal/diagnóstico , Arteriosclerosis Intracraneal/etiología , Pruebas del Lenguaje , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Diálisis Renal/efectos adversosRESUMEN
Experimental studies demonstrated that hypothyroidism can lead to depressive behavior and that thyroid hormones can have antidepressant effects. Postnatal changes in local blood flow in the dorsal hippocampus and cerebellar cortex were studied in the offspring of rats kept in conditions of iodine deficiency at conception and throughout gestation. The data obtained from these studies showed that severe limitation of iodine intake before and during gestation leads to marked deficiency in the blood supply to both of these brain structures, though the decrease in local blood flow in the dorsal hippocampus was more marked. Addition of iodine to the diet of females prevented this deficit of blood flow in both structures.
Asunto(s)
Corteza Cerebelosa/irrigación sanguínea , Circulación Cerebrovascular/fisiología , Hipocampo/irrigación sanguínea , Yodo/deficiencia , Efectos Tardíos de la Exposición Prenatal , Alimentación Animal , Animales , Corteza Cerebelosa/crecimiento & desarrollo , Corteza Cerebelosa/metabolismo , Femenino , Hipocampo/crecimiento & desarrollo , Hipocampo/metabolismo , Yodo/metabolismo , Intercambio Materno-Fetal , Neuronas/metabolismo , Embarazo , Ratas , Receptores de Hormona Tiroidea/metabolismo , Hormonas Tiroideas/fisiología , Oligoelementos/deficiencia , Oligoelementos/metabolismoRESUMEN
The interactions of epilepsy and antiepileptic therapy an one hand and cardiovascular system on the other hand are multiple and complex. Antiepileptic drugs (AEDs) cause alterations of serum lipids and of the fatty acid composition of the membranes. Homocystein, known to induce vascular endothelial damage was found to be elevated in patients on valproate (VPA) and carbamazepine (CBZ) therapy. Marked coronary artherosclerosis and myocardial infarction may already occur in children treated with CBZ. Community based studies corroborated a higher incidence of myocardial infarction, peripheral vascular diseases hypercholesterinemia, left ventricle hypertrophy and stroke in patients with epilepsy. In this context, we wanted to elevate changes of microcirculation related to AEDs commonly prescribed such as VPA and CBZ. Capillary microscopy is a non-invasive technique for measuring the velocity of red blood cells and for determining nutritional blood flow in the capillaries of the skin. It can easily be performed in children. The aim of this study was to look for possible effects an antiepileptic monotherapy with carbamazepine or valproate has on the peripheral microcirculation in epileptic children. We were able to examine 14 children with CBZ and 24 children with VPA, recruited in our neuropediatric Unit. The results were compared to normative values, determined in former analyses of 207 healthy children. We found significant differences in capillary density, tortuous index of the capillaries, capillary diameter and flow rate of erythrocytes for both antiepileptic drugs. Additionally, there were changes in plasma viscosity and the aggregation of erythrocytes. These microcapillary effects could be of special interest in the relationship of a long-term antiepileptic therapy and the development of vascular diseases. We suggest that the influence of AEDs on microcirculation should also be considered in further studies on cardiovascular changes in patients with antiepileptic long-term medication.
Asunto(s)
Anticonvulsivantes/farmacología , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Capilares/efectos de los fármacos , Carbamazepina/farmacología , Epilepsia/tratamiento farmacológico , Ácido Valproico/farmacología , Adolescente , Capilares/fisiopatología , Corteza Cerebelosa/irrigación sanguínea , Niño , Epilepsia/fisiopatología , Femenino , Hemorreología/efectos de los fármacos , Humanos , Masculino , Microcirculación/efectos de los fármacos , Microscopía/métodosRESUMEN
Experimental studies show depressive behavior in rats caused by hypothyroidism and antidepressant effect of thyroid hormones. The present study analyses changes in the hippocampal and cerebellar cortex local blood flow in the progeny of rats suffering from iodine deficiency before mating and during the whole period of gestation. The diet with very low iodine content results in a decrease of local blood flow in both brain structures, but the greatest changes were observed in hippocampus. Addition of the iodine to the diet eliminates the above blood flow changes.
Asunto(s)
Corteza Cerebelosa/irrigación sanguínea , Hipocampo/irrigación sanguínea , Hipotiroidismo/complicaciones , Yodo/deficiencia , Intercambio Materno-Fetal , Complicaciones del Embarazo/metabolismo , Efectos Tardíos de la Exposición Prenatal , Animales , Animales Recién Nacidos , Corteza Cerebelosa/embriología , Corteza Cerebelosa/crecimiento & desarrollo , Circulación Cerebrovascular , Trastornos Cerebrovasculares/congénito , Trastornos Cerebrovasculares/etiología , Trastornos Cerebrovasculares/fisiopatología , Femenino , Hipocampo/embriología , Hipocampo/crecimiento & desarrollo , Masculino , Embarazo , Complicaciones del Embarazo/sangre , Ratas , Flujo Sanguíneo Regional , Tiroxina/sangre , Tiroxina/metabolismo , Triyodotironina/sangre , Triyodotironina/metabolismoRESUMEN
Ischemic depolarizing events, such as repetitive spontaneous periinfarct spreading depolarizations (PIDs), expand the infarct size after experimental middle cerebral artery (MCA) occlusion. This worsening may result from increased metabolic demand, exacerbating the mismatch between cerebral blood flow (CBF) and metabolism. Here, we present data showing that anoxic depolarization (AD) and PIDs caused vasoconstriction and abruptly reduced CBF in the ischemic cortex in a distal MCA occlusion model in mice. This reduction in CBF during AD increased the area of cortex with 20% or less residual CBF by 140%. With each subsequent PID, this area expanded by an additional 19%. Drugs that are known to inhibit cortical spreading depression (CSD), such as N-methyl-D-aspartate receptor antagonists MK-801 and 7-chlorokynurenic acid, and sigma-1 receptor agonists dextromethorphan and carbetapentane, did not reduce the frequency of PIDs, but did diminish the severity of episodic hypoperfusions, and prevented the expansion of severely hypoperfused cortex, thus improving CBF during 90 mins of acute focal ischemia. In contrast, AMPA receptor antagonist NBQX, which does not inhibit CSD, did not impact the deterioration in CBF. When measured 24 h after distal MCA occlusion, infarct size was reduced by MK-801, but not by NBQX. Our results suggest that AD and PIDs expand the CBF deficit, and by so doing negatively impact lesion development in ischemic mouse brain. Mitigating the vasoconstrictive neurovascular coupling during intense ischemic depolarizations may provide a novel hemodynamic mechanism of neuroprotection by inhibitors of CSD.
Asunto(s)
Corteza Cerebelosa/fisiopatología , Infarto de la Arteria Cerebral Media/fisiopatología , Animales , Corteza Cerebelosa/irrigación sanguínea , Corteza Cerebelosa/metabolismo , Corteza Cerebelosa/patología , Circulación Cerebrovascular/efectos de los fármacos , Modelos Animales de Enfermedad , Agonistas de Aminoácidos Excitadores/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Ratones , Fármacos Neuroprotectores/farmacología , Receptores de N-Metil-D-Aspartato/agonistas , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Vasoconstricción/efectos de los fármacosRESUMEN
Three-dimensional (3D) visualization of microscopic structures may provide useful information about the exact 3D configuration, and offers a useful tool to examine the spatial relationship between different components in tissues. A promising field for 3D investigation is the microvascular architecture in normal and pathological tissue, especially because pathological angiogenesis plays a key role in tumor growth and metastasis formation. This paper describes an improved method for 3D reconstruction of microvessels and other microscopic structures in transmitted light microscopy. Serial tissue sections were stained for the endothelial marker CD34 to highlight microvessels and corresponding images were selected and aligned. Alignment of stored images was further improved by automated non-rigid image registration, and automated segmentation of microvessels was performed. Using this technique, 3D reconstructions were produced of the vasculature of the normal brain. Also, to illustrate the complexity of tumor vasculature, 3D reconstructions of two brain tumors were performed: a hemangioblastoma and a glioblastoma multiforme. The possibility of multiple component visualization was shown in a 3D reconstruction of endothelium and pericytes of normal cerebellar cortex and a hemangioblastoma using alternate staining for CD34 and alpha-smooth muscle actin in serial sections, and of a GBM using immunohistochemical double staining. In conclusion, the described 3D reconstruction procedure provides a promising tool for simultaneous visualization of microscopic structures.
Asunto(s)
Neoplasias Encefálicas/irrigación sanguínea , Neoplasias Encefálicas/patología , Microvasos/patología , Neovascularización Patológica/patología , Adhesión en Parafina , Corteza Cerebelosa/irrigación sanguínea , Corteza Cerebelosa/patología , Neoplasias Cerebelosas/irrigación sanguínea , Neoplasias Cerebelosas/patología , Glioblastoma/irrigación sanguínea , Glioblastoma/patología , Hemangioblastoma/irrigación sanguínea , Hemangioblastoma/patología , Humanos , Adhesión en Parafina/instrumentación , Adhesión en Parafina/métodosRESUMEN
OBJECTIVE: To evaluate the value of diffusion weighted imaging (DWI) in diagnosing ataxia telangiectasia (AT) and to investigate the spatial distribution of cerebral microstructural changes caused by the disease. METHODS: Six AT patients (9-13 years) and nine healthy control subjects were examined on 1.5 T scanner. In addition to conventional MR images, DWI were performed with a fat suppressed, multishot spin echo EPI sequence using B values of 0, 500 and 1000 s/mm2. Mean ADC values were measured from 16 different supra and infratentorial location. The difference between controls and AT patients regarding ADC values, and the accuracy, sensitivity and specificity of them in discrimination were analyzed with t-tests, logistic regression analysis, ANOVA and ROC curves. RESULTS: Conventional images of the controls were normal. In AT patients, the only conventional MR abnormality was cerebellar atrophy. The difference between both groups regarding mean ADC values was not significant for any of the cerebral structures. In contrary to cerebrum, cerebellar mean ADC values of patients and controls were statistically different (p < 0.011-0.0001). Patients and controls were classified with 100% accuracy using ADC values of cerebellar white matter and cortex together (p < 0.016). The cut-off ADC value (0.699 mm2/s) for middle cerebellar cortex had produced highest (100%) sensitivity and specificity. There was a difference between superior, middle and inferior cerebellar cortex regarding ADC values (p < 0.026). Superior cerebellar cortex (0.987+/-0.1956 mm2/s) had higher ADC values than the middle and inferior cerebellar cortex. CONCLUSION: DWI provides a supplementary and objective imaging finding in AT. This finding is highly accurate in the radiological discrimination of healthy subjects and AT. Our findings also implicate that AT causes a diffuse atrophy and mostly affects superior part of the cortex.
Asunto(s)
Ataxia Telangiectasia/diagnóstico , Encéfalo/patología , Imagen de Difusión por Resonancia Magnética/métodos , Adolescente , Atrofia , Encéfalo/irrigación sanguínea , Corteza Cerebelosa/irrigación sanguínea , Corteza Cerebelosa/patología , Cerebelo/irrigación sanguínea , Cerebelo/patología , Niño , Imagen Eco-Planar/métodos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Microcirculación/patología , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
Functional neuroimaging relies on the robust coupling between neuronal activity, metabolism and cerebral blood flow (CBF), but the physiological basis of the neuroimaging signals is still poorly understood. We examined the mechanisms of activity-dependent changes in tissue oxygenation in relation to variations in CBF responses and postsynaptic activity in rat cerebellar cortex. To increase synaptic activity we stimulated the monosynaptic, glutamatergic climbing fibres that excite Purkinje cells via AMPA receptors. We used local field potentials to indicate synaptic activity, and recorded tissue oxygen partial pressure (P(tiss,O2)) by polarographic microelectrodes, and CBF using laser-Doppler flowmetry. The disappearance rate of oxygen in the tissue increased linearly with synaptic activity. This indicated that, without a threshold, oxygen consumption increased as a linear function of synaptic activity. The reduction in P(tiss,O2) preceded the rise in CBF. The time integral (area) of the negative P(tiss,O2) response increased non-linearly showing saturation at high levels of synaptic activity, concomitant with a steep rise in CBF. This was accompanied by a positive change in P(tiss,O2). Neuronal nitric oxide synthase inhibition enhanced the initial negative P(tiss,O2) response ('dip'), while attenuating the evoked CBF increase and positive P(tiss,O2) response equally. This indicates that increases in CBF counteract activity-induced reductions in P(tiss,O2), and suggests the presence of a tissue oxygen reserve. The changes in P(tiss,O2) and CBF were strongly attenuated by AMPA receptor blockade. Our findings suggest an inverse relationship between negative P(tiss,O2) and CBF responses, and provide direct in vivo evidence for a tight coupling between activity in postsynaptic AMPA receptors and cerebellar oxygen consumption.
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Corteza Cerebelosa/irrigación sanguínea , Corteza Cerebelosa/fisiología , Potenciales Evocados/fisiología , Potenciales Postsinápticos Excitadores/fisiología , Neuronas/fisiología , Consumo de Oxígeno/fisiología , Oxígeno/metabolismo , Receptores AMPA/metabolismo , Potenciales de Acción/fisiología , Animales , Circulación Cerebrovascular/fisiología , Estimulación Encefálica Profunda/métodos , Masculino , Ratas , Ratas WistarRESUMEN
A patient with nocturnal frontal lobe epilepsy characterized by paroxysmal motor attacks during sleep had brief paroxysmal arousals (PAs), complex episodes of nocturnal paroxysmal dystonia, and epileptic nocturnal wandering since childhood. Ictal SPECT during an episode of PA demonstrated increased blood flow in the right anterior cingulate gyrus and cerebellar cortex with hypoperfusion in the right temporal and frontal associative cortices.
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Nivel de Alerta/fisiología , Circulación Cerebrovascular , Epilepsia del Lóbulo Frontal/fisiopatología , Giro del Cíngulo/fisiopatología , Trastornos del Inicio y del Mantenimiento del Sueño/fisiopatología , Vigilia/fisiología , Adulto , Corteza Cerebelosa/irrigación sanguínea , Corteza Cerebelosa/diagnóstico por imagen , Electroencefalografía , Epilepsia del Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/irrigación sanguínea , Lóbulo Frontal/diagnóstico por imagen , Giro del Cíngulo/irrigación sanguínea , Giro del Cíngulo/diagnóstico por imagen , Humanos , Masculino , Trastornos del Inicio y del Mantenimiento del Sueño/diagnóstico por imagen , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Lóbulo Temporal/irrigación sanguínea , Lóbulo Temporal/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
OBJECTIVE: To describe the bypass techniques, cranial base approaches, results of treatment, causes of failure, and lessons that are learned in patients with posterior circulation aneurysms requiring revascularization. METHODS: Retrospectively, 19 patients with posterior fossa aneurysms requiring revascularization procedures operated on between 1991 and 2002 were reviewed. Preoperative and postoperative clinical information, neurological examinations, imaging data, and updated follow-ups were reviewed. Patient outcome is reported as the most current Karnofsky Performance Scale score. RESULTS: A total of 22 arterial bypasses were performed in 19 patients for posterior fossa circulation aneurysms between 1991 and 2002. The mean follow-up was 41 months. Total graft patency rate (including patients requiring reoperation) was 86.4% (before) and 100% (after) salvage procedures. Patient outcome was 84.2% with Karnofsky Performance Scale score 80 to 90, and three deaths occurred perioperatively. Only one death could be attributed to the failure of the radial artery graft because of spasm and subsequent rupture during angioplasty. CONCLUSION: Certain graft selection criteria and technical considerations contribute to the success or failure of bypass grafts in the management of posterior circulation aneurysms. Bypass procedures remain an important method of management of complex posterior circulation aneurysms, in addition to endovascular procedures.