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In this issue of Cell, Zhang and Yatsev, 2019 and Kingsbury et al. (2019) provide insight into the emergence of synchronized neuronal activity between prefrontal cortices of two brains that share the same social context via electrophysiology recordings in bats and calcium-imaging in mice.
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Quirópteros , Animales , Encéfalo , Calcio , Ratones , NeuronasRESUMEN
Microglia, the brain-resident immune cells, are critically involved in many physiological and pathological brain processes, including neurodegeneration. Here we characterize microglia morphology and transcriptional programs across ten species spanning more than 450 million years of evolution. We find that microglia express a conserved core gene program of orthologous genes from rodents to humans, including ligands and receptors associated with interactions between glia and neurons. In most species, microglia show a single dominant transcriptional state, whereas human microglia display significant heterogeneity. In addition, we observed notable differences in several gene modules of rodents compared with primate microglia, including complement, phagocytic, and susceptibility genes to neurodegeneration, such as Alzheimer's and Parkinson's disease. Our study provides an essential resource of conserved and divergent microglia pathways across evolution, with important implications for future development of microglia-based therapies in humans.
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Evolución Molecular , Redes Reguladoras de Genes , Microglía/metabolismo , Enfermedades Neurodegenerativas/genética , Análisis de la Célula Individual , Transcriptoma , Animales , Pollos , Perfilación de la Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Primates , Reptiles , Roedores , Ovinos , Porcinos , Pez CebraRESUMEN
Parental care is found in species across the animal kingdom, from small insects to large mammals, with a conserved purpose of increasing offspring survival. Yet enormous variability exists between different species and between the sexes in the pattern and level of parental investment. Here, we review the literature on the neurobiological mechanisms underlying maternal and paternal care, especially in rodents, and discuss the relationship between sex differences in behavior and sexual dimorphism in the brain. We argue that although several brain regions and circuits regulating parental care are shared by both sexes, some of the fundamental components comprising the maternal brain are innate and sex specific. Moreover, we suggest that a more comprehensive understanding of the underlying mechanisms can be achieved by expanding the methodological toolbox, applying ethologically relevant approaches such as nontraditional wild-derived animal models and complex seminatural experimental set-ups.
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Conducta Animal/fisiología , Conducta Materna/fisiología , Conducta Paterna/fisiología , Caracteres Sexuales , Animales , Femenino , Expresión Génica , MasculinoRESUMEN
INTRODUCTION: Transdural collaterals (TC) from the external carotid artery must be preserved when operating on patients with moyamoya vasculopathy. Several techniques have been used to identify the superficial temporal artery (STA) and middle meningeal artery (MMA) during surgery and prevent their damage. However, the use of neuronavigation for this specific purpose has never been described in the literature. We describe an operative case in which neuronavigation was used to preserve the TC (originating from the MMA), detailing our technique step by step and reviewing alternative methods previously reported. CASE PRESENTATION: A 6-year-old girl with moyamoya disease, who had developed marked bilateral TC from the MMA sparing the middle cerebral artery territory, underwent staged bilateral indirect revascularization surgery. Intraoperative neuronavigation was used to identify the STA and MMA with their main branches during skin incision, craniotomy, and dural opening. The neuronavigation matched the intraoperative findings exactly, and the target structures remained undamaged. The patient was discharged home after both surgeries with no neurological deficits. One year following surgery, the patient has excellent collateralization from both STAs and is asymptomatic and neurologically intact. CONCLUSION: With the use of intraoperative neuronavigation, the STA, MMA, and their main branches, as well as their relationship to the bone, can be identified and preserved. This approach can help in preventing undesirable injury to TC during surgery and may potentially prevent perioperative stroke in patients with moyamoya vasculopathy undergoing revascularization surgery.
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Revascularización Cerebral , Enfermedad de Moyamoya , Revascularización Cerebral/métodos , Niño , Femenino , Humanos , Arterias Meníngeas , Arteria Cerebral Media , Enfermedad de Moyamoya/diagnóstico por imagen , Enfermedad de Moyamoya/etiología , Enfermedad de Moyamoya/cirugía , Neuronavegación , Resultado del TratamientoRESUMEN
BACKGROUND: For many animals, chemosensory cues are vital for social and defensive interactions and are primarily detected and processed by the vomeronasal system (VNS). These cues are often inherently associated with ethological meaning, leading to stereotyped behaviors. Thus, one would expect consistent representation of these stimuli across different individuals. However, individuals may express different arrays of vomeronasal sensory receptors and may vary in the pattern of connections between those receptors and projection neurons in the accessory olfactory bulb (AOB). In the first part of this study, we address the ability of individuals to form consistent representations despite these potential sources of variability. The second part of our study is motivated by the fact that the majority of research on VNS physiology involves the use of stimuli derived from inbred animals. Yet, it is unclear whether neuronal representations of inbred-derived stimuli are similar to those of more ethologically relevant wild-derived stimuli. RESULTS: First, we compared sensory representations to inbred, wild-derived, and wild urine stimuli in the AOBs of males from two distinct inbred strains, using them as proxies for individuals. We found a remarkable similarity in stimulus representations across the two strains. Next, we compared AOB neuronal responses to inbred, wild-derived, and wild stimuli, again using male inbred mice as subjects. Employing various measures of neuronal activity, we show that wild-derived and wild stimuli elicit responses that are broadly similar to those from inbred stimuli: they are not considerably stronger or weaker, they show similar levels of sexual dimorphism, and when examining population-level activity, cluster with inbred mouse stimuli. CONCLUSIONS: Despite strain-specific differences and apparently random connectivity, the AOB can maintain stereotypic sensory representations for broad stimulus categories, providing a substrate for common stereotypical behaviors. In addition, despite many generations of inbreeding, AOB representations capture the key ethological features (i.e., species and sex) of wild-derived and wild counterparts. Beyond these broad similarities, representations of stimuli from wild mice are nevertheless distinct from those elicited by inbred mouse stimuli, suggesting that laboratory inbreeding has indeed resulted in marked modifications of urinary secretions.
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Bulbo Olfatorio , Animales , Señales (Psicología) , Masculino , Ratones , Células Receptoras Sensoriales , Olfato , Conducta Estereotipada , Órgano VomeronasalRESUMEN
INTRODUCTION: The use of endovascular thrombectomy (EVT) has dramatically increased in recent years. However, most existing studies used an upper age limit of 80 and data regarding the safety and efficacy of EVT among nonagenarians is still lacking. METHODS: 767 consecutive patients undergoing EVT for large vessel occlusion (LVO) in three participating centers were recruited into a prospective ongoing database. Demographic, clinical and imaging characteristics were documented. Statistical analysis was done to evaluate EVT outcome among nonagenarians compared to younger patients. RESULTS: The current analysis included 41 (5.4%) patients older than 90 years. Compared to younger patients, nonagenarians were more often female (78% versus 50.3%, p ≤ 0.001), had worse baseline mRS scores (2 [0-3] versus 0 [0-2], p < 0.001), higher rates of hypertension and hyperlipidemia and a higher admission NIHSS (20 [14-23] versus 16 [11-20], p < 0.001). No differences were found between groups regarding the involved vessel, stroke etiology, time from symptoms to door or symptoms to EVT, successful recanalization rates and hemorrhagic transformation rates. Nonagenarians had worse mRS at 90 days (5 [3-6] versus 3 [2-5], p = 0.001), similar discharge NIHSS (5 [1-11] versus 4 [1-11], p = 0.78) and higher mortality rates (36.6% versus 15.8%, p < 0.001). All nonagenarians with baseline mRS 4 have died within 90 days. 36.4% of nonagenarian patients with baseline MRS of 3 or less had favorable outcome. DISCUSSION: This study demonstrates that nonagenarian stroke patients with baseline mRS of 3 or less benefit from EVT with no significant difference in the rate of favorable outcome compared to octogenarians.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular , Anciano de 80 o más Años , Isquemia Encefálica/diagnóstico , Estudios de Cohortes , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Femenino , Humanos , Nonagenarios , Estudios Prospectivos , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Trombectomía , Resultado del TratamientoRESUMEN
It is commonly assumed, but has rarely been demonstrated, that sex differences in behaviour arise from sexual dimorphism in the underlying neural circuits. Parental care is a complex stereotypic behaviour towards offspring that is shared by numerous species. Mice display profound sex differences in offspring-directed behaviours. At their first encounter, virgin females behave maternally towards alien pups while males will usually ignore the pups or attack them. Here we show that tyrosine hydroxylase (TH)-expressing neurons in the anteroventral periventricular nucleus (AVPV) of the mouse hypothalamus are more numerous in mothers than in virgin females and males, and govern parental behaviours in a sex-specific manner. In females, ablating the AVPV TH(+) neurons impairs maternal behaviour whereas optogenetic stimulation or increased TH expression in these cells enhance maternal care. In males, however, this same neuronal cluster has no effect on parental care but rather suppresses inter-male aggression. Furthermore, optogenetic activation or increased TH expression in the AVPV TH(+) neurons of female mice increases circulating oxytocin, whereas their ablation reduces oxytocin levels. Finally, we show that AVPV TH(+) neurons relay a monosynaptic input to oxytocin-expressing neurons in the paraventricular nucleus. Our findings uncover a previously unknown role for this neuronal population in the control of maternal care and oxytocin secretion, and provide evidence for a causal relationship between sexual dimorphism in the adult brain and sex differences in parental behaviour.
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Hipotálamo/citología , Hipotálamo/fisiología , Conducta Materna/fisiología , Oxitocina/metabolismo , Caracteres Sexuales , Agresión , Animales , Núcleo Hipotalámico Anterior/citología , Núcleo Hipotalámico Anterior/enzimología , Núcleo Hipotalámico Anterior/fisiología , Neuronas Dopaminérgicas/enzimología , Neuronas Dopaminérgicas/metabolismo , Femenino , Hipotálamo/enzimología , Masculino , Ratones , Oxitocina/sangre , Núcleo Hipotalámico Paraventricular/citología , Núcleo Hipotalámico Paraventricular/enzimología , Núcleo Hipotalámico Paraventricular/fisiología , Periodo Posparto , Sinapsis/metabolismo , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
BACKGROUND: Mechanical shunt malfunction may lead to significant morbidity and mortality. Shunt series assessments help evaluate shunt integrity; however, they are of limited value in the area of the skull due to skull curvature, thickness, and air sinuses. We describe the role of 3D bone reconstruction CT (3DCT) in demonstrating the shunt integrity over the skull, comparing this technique to skull X-rays (SXR). METHODS: Data were collected retrospectively for shunted patients with concurrent SXR and 3DCT and for patients presenting with shunt failures at the region of the skull, including clinical course and radiological findings. We compared the SXR and 3DCT findings. The 3DCT was reconstructed from standard diagnostic CT protocols performed during evaluation of suspected shunt malfunction and not thin-slice CT protocols. RESULTS: Forty-eight patients with 57 shunts underwent SXR and 3DCT. Interobserver agreement was high for most variables. Both SXR and 3DCT had a high sensitivity, specificity, and accuracy identifying tubing disconnections (between 0.83 and 1). Full valve type and setting were significantly more accurate based on SXR versus 3DCT (>90 vs. <20%), and valve integrity was significantly more readily verified on 3DCT versus SXR (100 vs. 52%). CONCLUSIONS: 3DCT and SXR complement each other in diagnosing mechanical shunt malfunctions over the skull. The main limitation of 3DCT is identification of valve type and settings, which are clearer on SXR, while the main limitation of SXR is a less ability to evaluate valve integrity. 3DCT also enables an intuitive 3D understanding of the shunt tubing over the skull.
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Imagenología Tridimensional , Tomografía Computarizada por Rayos X , Humanos , Radiografía , Estudios Retrospectivos , Cráneo/diagnóstico por imagen , Cráneo/cirugíaRESUMEN
BACKGROUND: The extent of tumor resection (EOTR) calculated by enhanced T1 changes in glioblastomas has been previously reported to predict survival. However, fluid-attenuated inversion recovery (FLAIR) volume may better represent tumor burden. In this study, we report the first assessment of the dynamics of FLAIR volume changes over time as a predictive variable for post-resection overall survival (OS). METHODS: Contemporary data from 103 consecutive patients with complete imaging and clinical data who underwent resection of newly diagnosed glioblastoma followed by the Stupp protocol between 2010 and 2013 were analyzed. Clinical, radiographic, and outcome parameters were retrieved for each patient, including magnetic resonance imaging (MRI)-based volumetric tumor analysis before, immediately after, and 3 months post-surgery. RESULTS: OS rate was 17.6 months. A significant incremental OS advantage was noted, with as little as 85 % T1-weighted gadolinium-enhanced (T1Gd)-EOTR measured on contrast-enhanced MRI. Pre- and immediate postoperative FLAIR-based EOTR was not predictive of OS; however, abnormal FLAIR volume measured 3 months post-surgery correlated significantly with outcome when FLAIR residual tumor volume (RTV) was <19.3 cm3 and <46 % of baseline volume (p < 0.0001 for both). Age and isocitrate dehydrogenase (IDH)-1 mutation were predictive of OS (p < 0.0001, Cox proportional hazards). CONCLUSIONS: OS correlated with the immediate postoperative T1Gd-EOTR measured by enhanced T1 MRI, but not by FLAIR volume. Diminished abnormal FLAIR volume at 3 months post-surgery was associated with OS benefit when FLAIR-RTV was <19.3 cm3 or <46 % of baseline. These threshold values provide a new radiological variable that can be used for prediction of OS in patients with glioblastoma immediately after completion of standard chemoradiation.
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Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Imagen de Difusión por Resonancia Magnética/métodos , Glioblastoma/diagnóstico por imagen , Glioblastoma/cirugía , Factores de Edad , Anciano , Neoplasias Encefálicas/patología , Medios de Contraste , Femenino , Gadolinio , Glioblastoma/patología , Humanos , Isocitrato Deshidrogenasa/genética , Masculino , Persona de Mediana Edad , Neoplasia Residual , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Periodo Preoperatorio , Estudios Retrospectivos , Tasa de Supervivencia , Carga TumoralRESUMEN
Genome-wide association studies and copy number variation analyses have linked contactin associated protein 2 (Caspr2, gene name Cntnap2) with autism spectrum disorder (ASD). In line with these findings, mice lacking Caspr2 (Cntnap2(-/-)) were shown to have core autism-like deficits including abnormal social behavior and communication, and behavior inflexibility. However the role of Caspr2 in ASD pathogenicity remains unclear. Here we have generated a new Caspr2:tau-LacZ knock-in reporter line (Cntnap2(tlacz/tlacz)), which enabled us to monitor the neuronal circuits in the brain expressing Caspr2. We show that Caspr2 is expressed in many brain regions and produced a comprehensive report of Caspr2 expression. Moreover, we found that Caspr2 marks all sensory modalities: it is expressed in distinct brain regions involved in different sensory processings and is present in all primary sensory organs. Olfaction-based behavioral tests revealed that mice lacking Caspr2 exhibit abnormal response to sensory stimuli and lack preference for novel odors. These results suggest that loss of Caspr2 throughout the sensory system may contribute to the sensory manifestations frequently observed in ASD.
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Encéfalo/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Percepción Olfatoria/fisiología , Animales , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/metabolismo , Proteínas de la Membrana/genética , Ratones , Ratones Transgénicos , Proteínas del Tejido Nervioso/genética , OdorantesRESUMEN
BACKGROUND: Acute ischemic stroke (AIS) is a common neurological event that causes varying degrees of disability. AIS outcome varies considerably, from complete recovery to complete loss of tissue and function. This diversity is partly explained by the compensatory ability of the collateral circulation and the ensuing cerebral flow grade. The collateral flow to the anterior circulation largely supplies the cortical areas. The deep brain tissue is supplied by penetrating arteries and has little or no collateral supply. Although these brain compartments differ substantially in their collateral supply, there are no published data on the different effects the collateral circulation has on them. In addition, the influence of baseline collateral flow on the final infarct size following endovascular or reperfusion therapies remains unknown. This study was designed to determine the effect of the collateral circulation on cortical infarct volume and deep infarct volume, and to investigate the relation between the collateral grade, response to reperfusion therapy and clinical outcome. METHODS: We studied consecutive patients presenting to our medical center between April 2008 and April 2012 with AIS and anterior proximal artery occlusion. To be included patients had to undergo a computerized tomographic angiographic study within 12 h of symptom onset demonstrating the occlusion. Imaging data and clinical and laboratory values were extracted retrospectively from the original scans and medical records. Cortical infarct volume (CIV) and deep infarct volume (DIV) were calculated as well as collateral grade. Clinical outcome was assessed at discharge using the modified Rankin Scale (mRS). RESULTS: Of the 51 study patients, 13 were treated conservatively, 22 received intravenous recombinant tissue plasminogen activator, and 16 received intra-arterial thrombolysis. The collateral grading was similar for all three treatment groups. While there was a moderate inverse correlation between the collateral grade and CIV (Spearman's rho = -0.49, P < 0.001), no comparable correlation was observed between the collateral grade and DIV (Spearman's rho =0.03, P = 0.85). Clinical outcome was significantly related to CIV but not to DIV (Spearman's rho =0.6 P < 0.001 versus Spearman's rho =0.09 P = 0.54, respectively). The correlation between the collateral grade and CIV was greatly diminished and lost its statistical significance in patients with successful recanalization (Spearman's rho = 0.2, p = 0.3). CONCLUSIONS: Our data shows that the collateral circulation is an important determinant of cortical infarct volume and, in turn, of clinical outcome in the setting of anterior circulation major artery occlusion. Our findings further demonstrate the benefit of recanalization in sparing cortical tissue from injury. Additional studies are needed to determine the impact of stroke therapy on the final infarct volume in relation to the collateral grade.
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Isquemia Encefálica , Circulación Cerebrovascular/fisiología , Circulación Colateral/fisiología , Accidente Cerebrovascular , Anciano , Infarto Encefálico/diagnóstico por imagen , Infarto Encefálico/fisiopatología , Infarto Encefálico/terapia , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/fisiopatología , Isquemia Encefálica/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/terapia , Resultado del TratamientoRESUMEN
OBJECTIVE Preoperative embolization is performed before spine tumor surgery when significant intraoperative hemorrhage is anticipated. Occlusion of radicular and segmental arteries may result in spinal ischemia. The goal of this study was to check whether neurophysiological monitoring during preoperative angiography in patients scheduled for total en bloc spondylectomy (TES) of spine tumors improves the safety of vessel occlusion. METHODS This was a case series study of patients who underwent tumor embolization under somatosensory evoked potential (SSEP) and motor evoked potential (MEP) monitoring in preparation for TES in treating spine tumors. The angiography findings, the embolized vessels, and the results are presented. RESULTS Five patients whose ages ranged from 33 to 75 years and who had thoracic spine tumors are reported. Four patients suffered from primary tumor and 1 patient had a metastatic tumor. Radicular arteries at the tumor level, 1 level above, and 1 level below were permanently occluded when SSEPs and MEPs were preserved during temporary occlusion. No complications were encountered during or after the angiography procedure and embolization. CONCLUSIONS Temporary occlusion with electrophysiological monitoring during preoperative angiography may improve the safety of permanent radicular artery occlusion, including the artery of Adamkiewicz in patients undergoing TES for the treatment of spine tumors.
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Angiografía/métodos , Monitorización Neurofisiológica Intraoperatoria/métodos , Cuidados Preoperatorios/métodos , Isquemia de la Médula Espinal/diagnóstico por imagen , Isquemia de la Médula Espinal/cirugía , Adulto , Anciano , Potenciales Evocados Motores/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: Stroke imaging studies during the acute phase are likely to precede several vascular brain mechanisms, which have an important role in patient outcome. The aim of this study was to identify within the lesion area during the subacute phase (≥1 day) reactive tissue, which may have the potential for recovery. METHODS: Twenty seven stroke patients from two cohorts were included. MRI performed during the subacute phase included conventional, perfusion and diffusion imaging. In cohort I, unsupervised multiparametric classification of the lesion area was performed. In cohort II threshold based classification was performed during the subacute phase, and radiological outcome was assessed at follow-up scan. RESULTS: Three tissue classes were identified in cohort I, referred to as irreversibly damaged, intermediary, and reactive tissue. Based on threshold values defined in cohort I, the reactive tissue was identified in 11/13 patients in cohort II, and showed tissue preservation/partial recovery in 9/11 patients at follow-up scan. The irreversibly damaged tissue was identified in 7/13 patients in cohort II, and predicted tissue necrosis in all cases. CONCLUSION: Identification of reactive tissue following stroke during the subacute phase can improve radiological assessment, contribute to the understanding of brain recovery processes and has implications for new therapeutic approaches.
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Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Accidente Cerebrovascular/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Imagen de Difusión por Resonancia Magnética , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Necrosis , Accidente Cerebrovascular/tratamiento farmacológico , Activador de Tejido Plasminógeno/uso terapéuticoRESUMEN
Maternal malnutrition has been associated with neurodevelopmental deficits and long-term implications on the offspring's health and behavior. Here, we investigated the effects of maternal low-protein diet (LPD) or obesity-inducing maternal high-fat diet (HFD) on dyadic social interactions, group organization and autism-related behaviors in mice. We found that maternal HFD induced an autism-related behavioral phenotype in the male offspring, including a robust decrease in sociability, increased aggression, cognitive rigidity and repetitive behaviors. Maternal LPD led to a milder yet significant effect on autism-related symptoms, with no effects on olfactory-mediated social behavior. Under naturalistic conditions in a group setting, this manifested in altered behavioral repertoires, increased magnitude in dominance relations, and reduced interactions with novel social stimuli in the HFD male offspring, but not in the LPD offspring. Finally, we found HFD-induced transcriptomic changes in the olfactory bulbs of the male offspring. Together, our findings show that maternal malnutrition induces long-lasting effects on aggression and autism-related behaviors in male offspring, and potential impairments in brain regions processing chemosensory signals.
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Trastorno Autístico , Conducta Animal , Dieta Alta en Grasa , Dieta con Restricción de Proteínas , Conducta Social , Animales , Dieta Alta en Grasa/efectos adversos , Femenino , Masculino , Ratones , Trastorno Autístico/etiología , Trastorno Autístico/metabolismo , Embarazo , Dieta con Restricción de Proteínas/efectos adversos , Agresión , Efectos Tardíos de la Exposición Prenatal/metabolismo , Ratones Endogámicos C57BL , Fenómenos Fisiologicos Nutricionales Maternos , Bulbo Olfatorio/metabolismo , Modelos Animales de Enfermedad , Obesidad/metabolismo , Obesidad/etiologíaRESUMEN
In nature, both males and females engage in competitive aggressive interactions to resolve social conflicts, yet the behavioral principles guiding such interactions and their underlying neural mechanisms remain poorly understood. Through circuit manipulations in wild mice, we unveil oxytocin-expressing (OT+) neurons in the hypothalamic paraventricular nucleus (PVN) as a neural hub governing behavior in dyadic and intragroup social conflicts, influencing the degree of behavioral sexual dimorphism. We demonstrate that OT+ PVN neurons are essential and sufficient in promoting aggression and dominance hierarchies, predominantly in females. Furthermore, pharmacogenetic activation of these neurons induces a change in the 'personality' traits of the mice within groups, in a sex-dependent manner. Finally, we identify an innervation from these OT neurons to the ventral tegmental area that drives dyadic aggression, in a sex-specific manner. Our data suggest that competitive aggression in naturalistic settings is mediated by a sexually dimorphic OT network connected with reward-related circuitry.
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Agresión , Neuronas , Oxitocina , Núcleo Hipotalámico Paraventricular , Caracteres Sexuales , Animales , Oxitocina/metabolismo , Agresión/fisiología , Femenino , Masculino , Ratones , Núcleo Hipotalámico Paraventricular/fisiología , Neuronas/fisiología , Conducta Social , Área Tegmental Ventral/fisiología , Conflicto Psicológico , Ratones Endogámicos C57BLRESUMEN
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic) syndrome is a newly described hemato-inflammatory acquired monogenic entity that presents in adulthood. One of the main features of VEXAS syndrome is a high venous thromboembolism (VTE) burden, with approximately 30-40% experiencing lower extremity deep vein thrombosis and a lower incidence of pulmonary embolism at approximately 10%. To date, VEXAS syndrome has not been associated with rarer forms of VTE such as cerebral sinus vein thrombosis (CSVT) and Budd-Chiari syndrome, which are well-recognized vascular manifestations in Behcet's disease, another autoinflammatory vasculitic disease. Herein, we describe a case of acute severe extensive and fatal CSVT in a patient with VEXAS syndrome. The event occurred during a period of apparently quiescent inflammatory status, while the patient was receiving tocilizumab and a low dose of glucocorticoids. Despite treatment with anticoagulation, high-dose glucocorticoids, endovascular thrombectomy, and intracranial pressure-lowering agents, the patient suffered severe neurologic damage and ultimately succumbed to the condition 3 weeks after the onset of CSVT. To the best of our knowledge, this is the first reported case of CVST in a patient with VEXAS syndrome.
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Infratentorial gliomas are relatively rare tumors compared to their supratentorial counterparts. As such they have not been extensively characterized as a group and are usually excluded from clinical studies. Using our database we aimed to characterize adult gliomas involving the posterior fossa with respect to their clinical behavior and prognostic factors. We reviewed our neurosurgical and neuro-oncological data bases for adult patients diagnosed with gliomas involving the posterior fossa between 1996 and 2010. Of 1,283 glioma patients, 57 patients with gliomas involving the posterior fossa were identified (4.4 %). Tumors were further classified by location as primary brainstem (n = 21) and primary cerebellar (n = 18) tumors. On univariate analysis survival was correlated to tumor grade and KPS. In addition we have identified a unique group of patients (n = 18) with previously diagnosed supratentorial gliomas who subsequently developed noncontiguous secondary infratentorial extension of their tumors with subsequent rapid clinical deterioration. Gliomas of the posterior fossa comprise a heterogeneous group of tumors. Histological grade of the tumor was found to be the main prognostic factor. Survival of primary cerebellar gliomas is comparable to supra-tentorial gliomas, while brainstem gliomas in adults fare better than in the pediatric population. Secondary extension of supratentorial gliomas to the posterior fossa signifies a grave prognosis.
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Neoplasias Encefálicas/patología , Neoplasias del Tronco Encefálico/patología , Fosa Craneal Posterior/patología , Glioma/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/cirugía , Neoplasias del Tronco Encefálico/mortalidad , Neoplasias del Tronco Encefálico/cirugía , Estudios de Cohortes , Fosa Craneal Posterior/cirugía , Femenino , Estudios de Seguimiento , Glioma/mortalidad , Glioma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Tasa de Supervivencia , Adulto JovenRESUMEN
In mice, pheromone detection is mediated by the vomeronasal organ and the main olfactory epithelium. Male mice that are deficient for Trpc2, an ion channel specifically expressed in VNO neurons and essential for VNO sensory transduction, are impaired in sex discrimination and male-male aggression. We report here that Trpc2-/- female mice show a reduction in female-specific behaviour, including maternal aggression and lactating behaviour. Strikingly, mutant females display unique characteristics of male sexual and courtship behaviours such as mounting, pelvic thrust, solicitation, anogenital olfactory investigation, and emission of complex ultrasonic vocalizations towards male and female conspecific mice. The same behavioural phenotype is observed after VNO surgical removal in adult animals, and is not accompanied by disruption of the oestrous cycle and sex hormone levels. These findings suggest that VNO-mediated pheromone inputs act in wild-type females to repress male behaviour and activate female behaviours. Moreover, they imply that functional neuronal circuits underlying male-specific behaviours exist in the normal female mouse brain.