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INTRODUCTION: In Rwanda, maternal community health workers play a critical role to improving maternal, newborn and child health, but little is known about their specific experiences with adolescent mothers, who face unique challenges, including trauma, ongoing violence, stigma, ostracism, mental health issues, barriers within the healthcare system, and lack of access to the social determinants of health. This study explored the experiences of maternal community health workers when caring for adolescent mothers in Rwanda to inform the delivery of trauma- and violence-informed care in community maternal services. METHODS: Interpretive Description methodology was used to understand the experiences of 12 community health workers purposively recruited for interviews due to their management roles. To gain additional insights about the context, seven key informants were also interviewed. FINDINGS: Maternal community health workers provided personalized support to adolescent mothers through the provision of continuity of care, acting as a liaison, engaging relationally and tailoring home visits. They reported feeling passionate about their work, supporting each other, and receiving support from their leaders as facilitators in caring for adolescent mothers. Challenges in their work included handling disclosures of violence, dealing with adolescent mothers' financial constraints, difficulties accessing these young mothers, and transportation issues. Adolescent mothers' circumstances are generally difficult, leading to self-reports of vicarious trauma among this sample of workers. CONCLUSION: Maternal community health workers play a key role in addressing the complex needs of adolescent mothers in Rwanda. However, they face individual and structural challenges highlighting the complexities of their work. To sustain and enhance their roles, it is imperative for government and other stakeholders to invest in resources, mentorship, and support. Additionally, training in equity-oriented approaches, particularly trauma- and violence-informed care, is essential to ensure safe and effective care for adolescent mothers and to mitigate vicarious trauma among maternal community health workers.
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Agentes Comunitarios de Salud , Embarazo en Adolescencia , Investigación Cualitativa , Humanos , Rwanda , Adolescente , Femenino , Agentes Comunitarios de Salud/psicología , Embarazo en Adolescencia/psicología , Embarazo , Madres/psicología , Violencia/psicología , Servicios de Salud Materna , Adulto , Entrevistas como AsuntoRESUMEN
OBJECTIVES: In 2016, a Pediatric Nursing Continuing Professional Development (PNCPD) program was created and implemented in Kigali, Rwanda, through the Training, Support, and Access Model (TSAM) for Maternal, Newborn, and Child Health (MNCH). This partnership project between Canada and Rwanda provided pediatric nursing education to forty-one Rwandan nurses and nurse educators in 2018 and 2019. The objective of this research study was to explore the experiences of nurses and nurse educators applying pediatric knowledge and skills to academic and clinical settings after participating in the PNCPD program. METHODS: This study was situated within an interpretive descriptive perspective to explore the ways in which knowledge gained during the PNCPD program in Rwanda was applied by nurses and nurse educators in their nursing practice, both academically and clinically. Data was collected through individual interviews. Inductive content analysis was used for data analysis. RESULTS: The analysis of the interviews resulted in the emergence of five themes: Transformations in Pediatric Nursing Practice, Knowledge Sharing, Relationship-Based Nursing, Barriers and Facilitators to Knowledge Implementation, and Scaling-up PNCPD within the Health System. CONCLUSIONS: The results of this study have the potential to inform positive changes to child health care in Rwanda, including scaling up pediatric nursing education to other areas of the healthcare system.
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Educación en Enfermería , Enfermeras y Enfermeros , Niño , Docentes de Enfermería , Humanos , Recién Nacido , Enfermería Pediátrica/educación , RwandaRESUMEN
BACKGROUND: The shortage of health care providers (HCPs) and inequity in their distribution along with the lack of sufficient and equal professional development opportunities in low-income countries contribute to the high mortality and morbidity of women and newborns. Strengthening skills and building the capacity of all HCPs involved in Maternal and Newborn Health (MNH) is essential to ensuring that mothers and newborns receive the required care in the period around birth. The Training, Support, and Access Model (TSAM) project identified onsite mentorship at primary care Health Centers (HCs) as an approach that could help reduce mortality and morbidity through capacity building of HCPs in Rwanda. This paper presents the results and lessons learnt through the design and implementation of a mentorship model and highlights some implications for future research. METHODS: The design phase started with an assessment of the status of training in HCs to inform the selection of Hospital-Based Mentors (HBMs). These HBMs took different courses to become mentors. A clear process was established for engaging all stakeholders and to ensure ownership of the model. Then the HBMs conducted monthly visits to all 68 TSAM assigned HCs for 18 months and were extended later in 43 HCs of South. Upon completion of 6 visits, mentees were requested to assist their peers who are not participating in the mentoring programme through a process of peer mentoring to ensure sustainability after the project ends. RESULTS: The onsite mentorship in HCs by the HBMs led to equal training of HCPs across all HCs regardless of the location of the HC. Research on this mentorship showed that the training improved the knowledge and self-efficacy of HCPs in managing postpartum haemorrhage (PPH) and newborn resuscitation. The lessons learned include that well trained midwives can conduct successful mentorships at lower levels in the healthcare system. The key challenge was the inconsistency of mentees due to a shortage of HCPs at the HC level. CONCLUSIONS: The initiation of onsite mentorship in HCs by HBMs with the support of the district health leaders resulted in consistent and equal mentoring at all HCs including those located in remote areas.
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Tutoría , Mentores , Atención a la Salud , Femenino , Humanos , Recién Nacido , Rwanda , Recursos HumanosRESUMEN
BACKGROUND: In Rwanda, maternal community health workers (M-CHWs) are involved in the country's overall health system. In maternal health, their role includes the provision of preventive and promotional health services at the community level. They provide services such as health education on maternal health wellbeing, advice and information on access and timely utilization of health facilities for prenatal, delivery and postpartum care. The contribution of M-CHWs in the health sector combined with other government initiatives led the country to achieving the fifth Millennium Development Goal (MDG) - target 5A- that aimed to improve maternal health through the reduction of maternal mortality ratio by 75% between 1990 and 2015). The objective of this study was to explore M-CHWs' perceptions and experiences on access and provision of maternal health services. METHODS: We used a case study methodology, a qualitative research approach to explore M-CHWs' experiences and perceptions on access and provision of maternal health services at the community level in Rwanda. For the period of June-August 2014, in-depth interviews were conducted with sixteen M-CHWs who had been providing maternal health services in the Eastern Province of Rwanda. Participants shared their experiences and perceptions on access and provision of maternal health service in their communities. RESULTS: The results of this research highlight the role of M-CHWs in promoting the use of health facilities for prenatal care and delivery and the ways they use to reach out to women. Several challenges prohibit M-CHWs to deliver adequate maternal health services and these are related to the poor resources settings in which they operate. CONCLUSION: The results of this study highlight the experiences and perceptions of M-CHWs on the provision and access to maternal health services in their communities. The fact that M-CHWs are volunteers operating in limited resources settings with no formal training in maternal health and with considerable workloads translates into challenges regarding the quality and quantity of services they provide in their communities. Such challenges create an impact on M-CHWs service provision, satisfaction and retention. The voices of M-CHWs and the communities they serve are needed to explore areas that are specific to each community context that would contribute to making the M-CHW program sustainable to achieve equitable access to maternal health services.
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Agentes Comunitarios de Salud/psicología , Servicios de Salud Materna/organización & administración , Adulto , Agentes Comunitarios de Salud/estadística & datos numéricos , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Investigación Cualitativa , RwandaRESUMEN
BACKGROUND: Accumulation of simple gangliosides GM2 and GM3, and gangliosides with longer long-chain bases (d20:1) have been linked to toxicity and the pathogenesis of Alzheimer's disease (AD). Conversely, complex gangliosides, such as GM1, have been shown to be neuroprotective. Recent evidence using matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) has demonstrated that a-series gangliosides are differentially altered during normal aging, yet it remains unclear how simple species are shifting relative to complex gangliosides in the prodromal stages of AD. METHODS: Ganglioside profiles in wild-type (Wt) and transgenic APP21 Fischer rats were detected and quantified using MALDI-IMS at P0 (birth), 3, 12, and 20â¯months of age and each species quantified to allow for individual species comparisons. RESULTS: Tg APP21 rats were found to have a decreased level of complex gangliosides in a number of brain regions as compared to Wt rats and showed higher levels of simple gangliosides. A unique pattern of expression was observed in the white matter as compared to gray matter regions, with an age-dependent decrease in GD1 d18:1 species observed and significantly elevated levels of GM3 in Tg APP21 rats. CONCLUSIONS: These results are indicative of a pathological shift in ganglioside homeostasis during aging that is exacerbated in Tg APP21 rats. GENERAL SIGNIFICANCE: Ganglioside dysregulation may occur in the prodromal stages of neurodegenerative diseases like AD.
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Envejecimiento , Enfermedad de Alzheimer/metabolismo , Modelos Animales de Enfermedad , Gangliósidos/metabolismo , Homeostasis , Lípidos de la Membrana/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Enfermedad de Alzheimer/patología , Animales , Humanos , Ratas , Ratas Endogámicas F344RESUMEN
BACKGROUND AND PURPOSE: The objective of this work is to study the dose-dependent effect of combination therapy with dipyridamole and triflusal over that of triflusal alone on infarct size after middle cerebral artery occlusion (MCAO) ischemia. MATERIALS AND METHODS: Male Wistar rats were subjected to a permanent MCAO in the right hemisphere. Rats received triflusal alone and with dipyridamole via oral route. Three days after surgery, infarct volumes were measured. RESULTS: The lower dose regime of triflusal (10 mg/kg) and dipyridamole (200 mg/kg) caused the greatest decrease in infarct size compared with higher dose regime of triflusal (30 mg/kg) and dipyridamole (200 mg/kg) (P <.01), triflusal (30 mg/kg) alone (P <.07), and vehicle-treated controls. CONCLUSIONS: The lower dose combination of dipyridamole and triflusal appears to be more effective than triflusal alone after MCAO-induced cerebral ischemia. Therefore, there is a strong rationale to continue to examine the protective effects of triflusal and dipyridamole after cerebral ischemia.
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Encéfalo/efectos de los fármacos , Dipiridamol/farmacología , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Salicilatos/farmacología , Animales , Encéfalo/patología , Citoprotección , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Infarto de la Arteria Cerebral Media/patología , Masculino , Ratas WistarRESUMEN
Alzheimer's disease (AD) is the most common form of dementia, yet there are no therapeutic treatments that can either cure or delay its onset. Currently, the pathogenesis of AD is still uncertain, especially with respect to how the disease develops from a normal healthy brain. Amyloid ß oligomers (AßO) are highly neurotoxic proteins and are considered potential initiators to the pathogenesis of AD. Rat brains were exposed to AßO via bilateral intracerebroventricular injections. Rats were then euthanized at either 1, 3, 7 or 21-days post surgery. Rat behavioural testing was performed using the Morris water maze and open field tests. Post-mortem brain tissue was immunolabelled for Aß, microglia, and cholinergic neurons. Rats exposed to AßO showed deficits in spatial learning and anxiety-like behaviour. Acute positive staining for Aß was only observed in the corpus callosum surrounding the lateral ventricles. AßO exposed rat brains also showed a delayed increase in activated microglia within the corpus callosum and a decreased number of cholinergic neurons within the basal forebrain. Acute exposure to AßO resulted in mild learning and memory impairments with co-concomitant white matter pathology within the corpus callosum and cholinergic cell loss within the basal forebrain. Results suggest that acute exposure to AßO in the rat may be a useful tool in assessing the early phases for the pathogenesis of AD.
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Péptidos beta-Amiloides/toxicidad , Fragmentos de Péptidos/toxicidad , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/administración & dosificación , Animales , Ansiedad/metabolismo , Ansiedad/patología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Neuronas Colinérgicas/efectos de los fármacos , Neuronas Colinérgicas/metabolismo , Neuronas Colinérgicas/patología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/patología , Microglía/efectos de los fármacos , Microglía/metabolismo , Microglía/patología , Fragmentos de Péptidos/administración & dosificación , Ratas , Ratas Wistar , Memoria Espacial/efectos de los fármacosRESUMEN
NEW FINDINGS: What is the topic of this review? The pathways in the brain by which visceral information, in particular cardiopulmonary afferents, ascend to the cerebral cortex have been delineated in animal models. Studies using functional magnetic resonance imaging in humans have confirmed what was known from the animal studies and established the critical sites in the cerebral cortex of humans for autonomic control and the significance of these sites for cognitive emotional function. What advances does it highlight? Stimulation of cardiopulmonary afferents in humans has consistently resulted in activation in the insular cortex and the anterior cingulate cortex. It has been shown that individuals who are characterized as cardiovascular responders to mental stress have a different pattern of activity in the cortex related to the cardiac changes. A number of animal studies in the rat and cat have been particularly useful for determining the pathways and the sites in the forebrain and cortex that are responsible for autonomic control. For example, these experiments have demonstrated that there is a viscerotopically organized pathway, with the first site of termination in the nucleus of the solitary tract and with subsequent relays in the parabrachial nucleus and the ventroposterior parvocellular nucleus of the thalamus before final visceral afferent inputs in the insular cortex. Several neuroimaging studies in humans, using cardiopulmonary manipulations, have confirmed the importance of the insular cortex as a site of for visceral afferent inputs. The anterior cingulate cortex has also been implicated in cardiopulmonary control. Both the insular cortex and the infralimbic cortex have been shown to be involved in descending control of the cardiovascular system. Neuroimaging with functional magnetic resonance imaging has demonstrated that the cortical autonomic control pathways are different in individuals who are characterized as cardiovascular reactors to mental stress. There is evidence that this alteration in pathways in the cortex may be due to past experiences, including childhood trauma.
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Sistema Nervioso Autónomo/fisiología , Sistema Cardiovascular/inervación , Corteza Cerebral/fisiología , Vías Aferentes/fisiología , Animales , HumanosRESUMEN
Ischemic stroke often co-occurs with Alzheimer's disease (AD) leading to a worsened clinical outcome. Neuroinflammation is a critical process implicated in AD and ischemic pathology, associated with cognitive decline. We sought to investigate the combined effects of ischemic stroke induced by endothelin-1 injection in two AD rat models, using motor function, memory and microglial inflammation in the basal forebrain and striatum as readouts. In addition, we sought to determine the effectiveness of the antioxidant biologic CAT-SKL in one of the models. The early AD model employed the bilateral intracerebroventricular injections of the toxic ß-amyloid peptide Aß25-35, the prodromal AD model used the transgenic Fischer 344 rat overexpressing a pathological mutant human amyloid precursor protein. Motor function was assessed using a cylinder, modified sticky tape and beam-walk tasks; learning and memory were tested in the Morris water maze. Microglial activation was examined using immunohistochemistry. Aß25-35 toxicity and stroke combination greatly increased microglial inflammation in the basal forebrain. Prodromal AD-pathology coupled with ischemia in the transgenic rat resulted in a greater microgliosis in the striatum. Combined transgenic rats showed balance alterations, comorbid Aß25-35 rats showed a transient sensorimotor deficit, and both demonstrated spatial reference memory deficit. CAT-SKL treatment ameliorated memory impairment and basal forebrain microgliosis in Aß25-35 rats with stroke. Our results suggest that neuroinflammation could be one of the early processes underlying the interaction of AD with stroke and contributing to the cognitive impairment, and that therapies such as antioxidant CAT-SKL could be a potential therapeutic strategy.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Antioxidantes/metabolismo , Catalasa/metabolismo , Disfunción Cognitiva/metabolismo , Modelos Animales de Enfermedad , Inflamación/metabolismo , Aprendizaje por Laberinto/fisiología , Trastornos de la Memoria/metabolismo , Microglía/metabolismo , Ratas , Ratas Transgénicas , Accidente Cerebrovascular/patologíaAsunto(s)
Amiloide/química , Isquemia Encefálica/fisiopatología , Trastornos del Conocimiento/fisiopatología , Inflamación , Neuronas/patología , Accidente Cerebrovascular/fisiopatología , Animales , Isquemia Encefálica/complicaciones , Isquemia Encefálica/epidemiología , Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/epidemiología , Demencia/fisiopatología , Humanos , Modelos Teóricos , Enfermedades Neurodegenerativas/fisiopatología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/epidemiologíaRESUMEN
Considerable effort has been put into animal studies establishing the sites in the brain that are responsible for control of the autonomic nervous system. These studies relied on an electrophysiological or neurochemical response to the activation of peripheral autonomic receptors or chemical or electrical stimulation of central sites. A large number of excellent reviews summarize the results of these studies. More recently, functional imaging has been used to not only confirm the electrophysiological and anatomical studies in animals, but has allowed a more complete understanding of how the brain responds as a whole for effecting autonomic control. The earliest studies to examine forebrain control during functional imaging utilized tests that involved active participation of the subjects and included maximal inspiration, Valsalva manoeuvre, isometric handgrip and cold compress application. There were a few issues that arose from these studies. First, they involved areas of the brain that included active decision making, they were more prone to inducing movement artefact, and some of these tests could activate noxious regions in the brain in addition to autonomic sites. In fact, this dual modality activation represented a more severe complication for investigators determining nociceptive sites in the brain, since virtually all of their stimuli had concomitant autonomic responses. More recent investigations attempted to resolve these issues with more selective passive and active stimuli. In spite of the very different approaches taken to visceral activation in functional imaging studies, a consistent picture of the key areas involved in autonomic control has emerged.
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Sistema Nervioso Autónomo/fisiología , Encéfalo/fisiología , Neuroanatomía , Animales , Humanos , Neuroanatomía/métodosRESUMEN
Aberrations in brain microcirculation and the associated increase in blood-brain-barrier (BBB) permeability in addition to neuroinflammation and Aß deposition observed in Alzheimer's disease (AD) and ischemia have gained considerable attention recently. However, the role of microvascular homeostasis as a pathogenic substrate to disturbed microperfusion as well as an overlapping etiologic mechanism between AD and ischemia has not been thoroughly explored. In this study, we employ temporal histopathology of cerebral vasculature in a rat model of ß-amyloid (Aß) toxicity and endothelin-1 induced-ischemia (ET1) to investigate the panorama of cerebral pathology and the protein expression on d1, d7, and d28 post-injury. The combination of Aß and ET1 pathological states leads to an alteration in microvascular anatomy, texture, diameter, density, and protein expression, in addition to disturbed vessel-matrix-connections, inter-compartmental water exchange and basement membrane profile within the lesion epicenter localized in the striatum of Aß+ET1 brains compared to Aß and ET1 rats. We conclude that the neural microvascular network, in addition to the neural tissue, is not only sensitive to structural deterioration but also serves as an underlying vascular etiology between ischemia and AD pathologies. Such investigation can provide prospects to appreciate the interrelationships between structure and responses of cerebral microvasculature and to provide a venue for vascular remodeling as a new treatment strategy.
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The Sustainable Development Goals (SDGs) in part aim to further improve maternal health outcomes by reducing spatial disparities in utilization of critical services such as antenatal and assisted delivery, with emphasis on decentralization and integration of strategies. Yet, our understanding of within country spatial disparities in maternal health services (MHS) utilization over time has been scant. By fitting multiple regression models to a pooled dataset of the 2010/11 and 2014/15 Rwanda Demographic and Health Surveys (nâ¯=â¯12,273), and employing post-estimation margins analysis, we examined spatial differentiation of MHS trends prior to the SDGs in Rwanda. Our study found that women in 2014/15 were more likely to utilize antenatal services and assisted delivery (ORâ¯=â¯1.757, pâ¯≤â¯0.001) compared with 2010/11, but with nuanced spatial variations. Compared with Nyarugenge, women in nineteen out of the twenty-nine remaining districts were more likely to report utilization of antenatal services and skilled birth delivery, while the probability of accessing four or more antenatal services in seven districts declined between 2010/11 and 2014/15. Physical, financial and socio-cultural factors were associated with maternal health service utilization over the period. Based on our findings, we present policy suggestions for improving utilization of MHS in Rwanda and in similar contexts in the SDGs period.
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Disparidades en Atención de Salud/estadística & datos numéricos , Servicios de Salud Materna/normas , Aceptación de la Atención de Salud/estadística & datos numéricos , Humanos , Servicios de Salud Materna/estadística & datos numéricos , Rwanda , Análisis Espacio-Temporal , Desarrollo Sostenible/tendenciasRESUMEN
Perturbations of ganglioside homeostasis have been observed following stroke whereby toxic simple gangliosides GM2 and GM3 accumulate, while protective complex species GM1 and GD1 are reduced. Thus, there is a need for therapeutic interventions which can prevent ganglioside dysregulation after stroke. A pharmacological intervention using chloroquine was selected for its transient lysosomotropic properties which disrupt the activity of catabolic ganglioside enzymes. Chloroquine was administered both in vitro (0.1 µM), to primary cortical neurons exposed to GM3 toxicity, and in vivo (45 mg/kg i.p.), to 3-month-old male Wistar rats that underwent a severe stroke injury. Chloroquine was administered for seven consecutive days beginning 3 days prior to the stroke injury. Gangliosides were examined using MALDI imaging mass spectrometry at 3 and 21 days after the injury, and motor deficits were examined using the ladder task. Chloroquine treatment prevented ganglioside dysregulation 3 days post-stroke and partially prevented complex ganglioside depletion 21 days post-stroke. Exogenous GM3 was found to be toxic to primary cortical neurons which was protected by chloroquine treatment. Motor deficits were prevented in the forelimbs of stroke-injured rats with chloroquine treatment and was associated with decreased inflammation, neurodegeneration, and an increase in cell survival at the site of injury. Chloroquine administration prevents ganglioside dysregulation acutely, protects against GM3 toxicity in neurons, and is associated with long-term functional and pathological improvements after stroke in the rat. Therefore, targeting lipid dysregulation using lysosomotropic agents such as chloroquine may represent a novel therapeutic avenue for stroke injuries.
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Conducta Animal , Cloroquina/farmacología , Gangliósidos/metabolismo , Homeostasis/efectos de los fármacos , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/patología , Animales , Conducta Animal/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Miembro Anterior/patología , Miembro Anterior/fisiopatología , Masculino , Actividad Motora/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Ratas Wistar , Accidente Cerebrovascular/fisiopatologíaRESUMEN
Objective: Cataplexy is a complicated and dynamic process in narcolepsy type 1 (NT1) patients. This study aimed to clarify the distinct stages during a cataplectic attack and identify the changes of the primary motor cortex (PMC) excitability during these stages. Methods: Thirty-five patients with NT1 and 29 healthy controls were recruited to this study. Cataplectic stages were distinguished from a cataplectic attack by video-polysomnogram monitoring. Transcranial magnetic stimulation motor-evoked potential (TMS-MEP) was performed to measure the excitability of PMC during quiet wakefulness, laughter without cataplexy, and each cataplectic stage. Results: Based on the video and electromyogram observations, a typical cataplectic attack (CA) process is divided into four stages: triggering (CA1), resisting (CA2), atonic (CA3), and recovering stages (CA4). Compared with healthy controls, NT1 patients showed significantly decreased intracortical facilitation during quiet wakefulness. During the laughter stage, both patients and controls showed increased MEP amplitude compared with quiet wakefulness. The MEP amplitude significantly increased even higher in CA1 and 2, and then dramatically decreased in CA3 accompanied with prolonged MEP latency compared with the laughter stage and quiet wakefulness. The MEP amplitude and latency gradually recovered during CA4. Interpretation: This study identifies four stages during cataplectic attack and reveals the existence of a resisting stage that might change the process of cataplexy. The fluctuation of MEP amplitude and MEP latency shows a potential participation of PMC and motor control pathway during cataplexy, and the increased MEP amplitude during CA1 and 2 strongly implies a compensatory mechanism in motor control that may resist or avoid cataplectic attack.
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Cataplejía/fisiopatología , Potenciales Evocados Motores/fisiología , Corteza Motora/fisiología , Narcolepsia/fisiopatología , Adolescente , Adulto , Electromiografía/métodos , Femenino , Humanos , Risa/fisiología , Masculino , Persona de Mediana Edad , Estimulación Magnética Transcraneal/métodos , Adulto JovenRESUMEN
Ischemic stroke and diabetes are vascular risk factors for the development of impaired memory such as dementia and/or Alzheimer's disease. Clinical studies have demonstrated that minor striatal ischemic lesions in combination with ß-amyloid (Aß) load are critical in generating cognitive deficits. These cognitive deficits are likely to be associated with impaired insulin signaling. In this study, we examined the histological presence of insulin-like growth factor-I (IGF-1) and insulin receptor substrate (IRS-1) in anatomically distinct brain circuits compared with morphological brain damage in a co-morbid rat model of striatal ischemia (ET1) and Aß toxicity. The results demonstrated a rapid increase in the presence of IGF-1 and IRS-1 immunoreactive cells in Aß + ET1 rats, mainly in the ipsilateral striatum and distant regions with synaptic links to the striatal lesion. These regions included subcortical white matter, motor cortex, thalamus, dentate gyrus, septohippocampal nucleus, periventricular region and horizontal diagonal band of Broca in the basal forebrain. The alteration in IGF-1 and IRS-1 presence induced by ET1 or Aß rats alone was not severe enough to affect the entire brain circuit. Understanding the causal or etiologic interaction between insulin and IGF signaling and co-morbidity after ischemia and Aß toxicity will help design more effective therapeutics.
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Péptidos beta-Amiloides/metabolismo , Isquemia Encefálica/metabolismo , Trastornos del Conocimiento/metabolismo , Cuerpo Estriado/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Insulina/metabolismo , Trastornos de la Memoria/metabolismo , Transducción de Señal , Animales , Isquemia Encefálica/patología , Trastornos del Conocimiento/patología , Comorbilidad , Cuerpo Estriado/patología , Modelos Animales de Enfermedad , Proteínas Sustrato del Receptor de Insulina/metabolismo , Masculino , Trastornos de la Memoria/patología , Ratas , Ratas WistarRESUMEN
Defect in brain microperfusion is increasingly recognized as an antecedent event to Alzheimer's disease (AD) and ischemia. Nevertheless, studies on the role of impaired microperfusion as a pathological trigger to neuroinflammation, Aß deposition as well as blood-brain barrier (BBB) disruption, and the etiological link between AD and ischemia are lacking. In this study, we employ in vivo sequential magnetic resonance imaging (MRI) and computed tomography (CT) imaging in a co-morbid rat model of ß-amyloid toxicity (Aß) and ischemia (ET1) with subsequent histopathology of striatal lesion core and penumbra at 1, 7, and 28 days post injury. Within 24 h, cerebral injury resulted in increased BBB permeability due to the dissolution of ß-dystroglycan (ß-DG) and basement membrane laminin by active matrix metalloproteinase9 (MMP9). As a result, net flow of circulating IgG down a hydrostatic gradient into the parenchyma led to vasogenic edema and impaired perfusion, thus increasing the apparent hyperintensity in true fast imaging with steady-state free precession (true FISP) imaging and acute hypoperfusion in CT. This was followed by a slow recruitment of reactive astroglia to the affected brain and depolarization of aquaporin4 (AQP4) expression resulting in cytotoxic edema-in an attempt to resolve vasogenic edema. On d28, functional BBB was restored in ET1 rats as observed by astrocytic MMP9 release, ß-DG stabilization, and new vessel formation. This was confirmed by reduced hyperintensity on true FISP imaging and normalized cerebral blood flow in CT. While, Aß toxicity alone was not detrimental enough, Aß+ET1 rats showed delayed differential expression of MMP9, late recruitment of astroglial cells, protracted loss of AQP4 depolarization, and thus delayed BBB restoration and cerebral perfusion.
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Barrera Hematoencefálica/lesiones , Barrera Hematoencefálica/patología , Regeneración Nerviosa , Péptidos beta-Amiloides/toxicidad , Animales , Acuaporina 4/metabolismo , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Astrocitos/patología , Membrana Basal/efectos de los fármacos , Membrana Basal/patología , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/fisiopatología , Isquemia Encefálica/patología , Isquemia Encefálica/fisiopatología , Circulación Cerebrovascular/efectos de los fármacos , Comorbilidad , Modelos Animales de Enfermedad , Inmunoglobulina G/metabolismo , Imagen por Resonancia Magnética , Masculino , Degeneración Nerviosa/patología , Degeneración Nerviosa/fisiopatología , Regeneración Nerviosa/efectos de los fármacos , Ratas WistarRESUMEN
BACKGROUND AND PURPOSE: In the elderly, cerebral ischemia (CI) occurs in the presence of high levels of amyloid. Neuroinflammation plays a critical role in the pathophysiology of Alzheimer's disease and CI. This study examined infarct size, neuroinflammation, and cognitive deficits over time in rat models of Alzheimer's disease and CI. METHODS: beta-amyloid toxicity was modeled using bilateral intracerebroventricular injections of beta-amyloid 25 to 35 peptides. CI was modeled using unilateral injections of the potent vasoconstrictor, endothelin-1, into the striatum. RESULTS: Infarct volumes were higher in the presence of amyloid and compared with the CI model alone. In the CI model alone, the infarct volume was significantly smaller 28 days after surgery compared with 7 days after surgery. However, when Alzheimer's disease and CI models were combined, the infarct volume was significantly larger 28 days after surgery compared with 7 days after surgery. The neuroinflammation in the region of the infarct was also significantly increased. The Barnes circular platform test showed time-dependent increases in memory and learning deficits in the beta-amyloid-treated rats that were even greater when beta-amyloid treatment was combined with CI. CONCLUSIONS: CI in the presence of high levels of amyloid results in progressive increases in infarct size, neuroinflammation, and cognitive deficits.
Asunto(s)
Enfermedad de Alzheimer/patología , Amiloide/biosíntesis , Infarto Cerebral/patología , Trastornos del Conocimiento/patología , Inflamación/patología , Enfermedades del Sistema Nervioso/patología , Animales , Encéfalo/patología , Isquemia Encefálica/patología , Modelos Animales de Enfermedad , Humanos , Memoria , Ratas , Ratas Wistar , Accidente Cerebrovascular/patología , Factores de TiempoRESUMEN
BACKGROUND AND PURPOSE: Neuroinflammation plays a critical role in the pathogenesis of cerebral ischemia. Triflusal, a selective cyclooxygenase-2, and its active metabolite 3-hydroxy-4-trifluoromethylbenzoic acid may inhibit apoptosis and inflammation after cerebral ischemia. An in vivo model of cerebral ischemia was used to investigate the effects of triflusal and aspirin treatment on infarct volume, and inflammation after cerebral ischemia in the rat. METHODS: Male Wistar rats were subjected to a permanent right-sided middle cerebral artery occlusion. Rats received oral administration of either triflusal or aspirin. After 3 days after surgery, immunostaining was used to detect neuroinflammatory cells and molecules, and infarct volumes were measured. RESULTS: Both triflusal and aspirin at a dose of 30 mg/kg but not 10 mg/kg significantly reduced infarct volume compared with vehicle treatment. Middle cerebral artery occlusion resulted in increased astrocyte and heat shock protein-27 (Hsp27) immunostaining in the ipsilateral cortex. Triflusal (30 mg/kg) or aspirin treatment (30 mg/kg) did not reduce the levels of GFAP or Hsp27 immunostaining. Triflusal (30 mg/kg) also significantly decreased the protein levels of IL-Ibeta but not nuclear factor kappa B or tumor necrosis factor-alpha in the cortex ipsilateral to the middle cerebral artery occlusion. CONCLUSIONS: The results suggest that triflusal and aspirin appear to be equally neuroprotective against middle cerebral artery occlusion-induced cerebral ischemia. Therefore, strong rationale exists to continue the neuroprotective examination of triflusal in brain injury.
Asunto(s)
Aspirina/administración & dosificación , Isquemia Encefálica/tratamiento farmacológico , Salicilatos/administración & dosificación , Animales , Isquemia Encefálica/patología , Modelos Animales de Enfermedad , Quimioterapia Combinada , Masculino , Ratas , Ratas WistarRESUMEN
In general, cardiac regulation is dominated by the sympathetic and parasympathetic nervous systems in men and women, respectively. Our recent study had revealed sex differences in the forebrain network associated with sympathoexcitatory response to baroreceptor unloading. The present study further examined the sex differences in forebrain modulation of cardiovagal response at the onset of isometric exercise. Forebrain activity in healthy men (n = 8) and women (n = 9) was measured using functional magnetic resonance imaging during 5 and 35% maximal voluntary contraction handgrip exercise. Heart rate (HR), mean arterial pressure (MAP), and muscle sympathetic nerve activity (MSNA) were collected in a separate recording session. During the exercise, HR and MAP increased progressively, while MSNA was suppressed (P < 0.05). Relative to men, women demonstrated smaller HR (8 +/- 2 vs. 18 +/- 3 beats/min) and MAP (3 +/- 2 vs. 11 +/- 2 mmHg) responses to the 35% maximal voluntary contraction trials (P < 0.05). Although a similar forebrain network was activated in both groups, the smaller cardiovascular response in women was reflected in a weaker insular cortex activation. Nevertheless, men did not show a stronger deactivation at the ventral medial prefrontal cortex, which has been associated with modulating cardiovagal activity. In contrast, the smaller cardiovascular response in women related to their stronger suppression of the dorsal anterior cingulate cortex activity, which has been associated with sympathetic control of the heart. Our findings revealed sex differences in both the physiological and forebrain responses to isometric exercise.