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1.
Nurs Educ Perspect ; 42(6): 365-370, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34352851

RESUMO

AIM: The aim of this study was to test Purkey's invitational theory to evaluate unique aspects of the learning environment in nursing education. BACKGROUND: Faculty evaluate student learning but rarely students' unique experiences within learning environments. METHOD: This interpretive phenomenological analysis explored students' perceptions of their prelicensure learning environments. Twelve participants from two private bachelor of science in nursing programs were interviewed about their experiences. RESULTS: Students' perceptions of what helped (invited) their learning and hindered (disinvited) their learning included thematic aspects of learning environments based on Purkey's theory: people, places, processes, policies, and programs. Findings illustrate facets of the learning environment often not considered by educators in planning learning environments most conducive to student learning. CONCLUSION: Purkey's theory is a plausible framework for nurse educators to evaluate learning environments from students' perspectives and may provide valuable data about the unique milieu that promotes or hinders successful learning.


Assuntos
Bacharelado em Enfermagem , Estudantes de Enfermagem , Docentes de Enfermagem , Humanos , Aprendizagem , Pesquisa em Educação em Enfermagem
2.
J Am Assoc Nurse Pract ; 31(3): 189-197, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30681649

RESUMO

BACKGROUND AND PURPOSE: Polycystic ovary syndrome (PCOS) is a complex metabolic disorder associated with clinical manifestations that could be psychologically distressing to adolescent girls considering the concern of body image during the developmental stage of adolescence. Poor psychological functioning is related to increased mortality, higher health care costs, and negative health outcomes. Coping has been identified as impacting health and adaptation to illness; therefore, the purpose was to examine coping and depression in adolescent girls with PCOS. METHODS: Adolescent girls, aged 13-18 years and diagnosed with PCOS completed questionnaires regarding coping and depression and participated in interviews. A convergent, parallel, mixed-method design was used. CONCLUSIONS: Girls perceived very little control over the aspects of PCOS, with menstrual irregularities and the threat of infertility reported as the most stressful and least controllable aspects of PCOS. Lower control was a predictor of greater depression among the participants. IMPLICATIONS FOR PRACTICE: Providers should strive to establish rapport with adolescent girls and ask specifically about their concerns surrounding PCOS to provide meaningful health education. Providers should also be aware of the risk for depression among this population and should routinely screen patients and keep channels of communication open regarding the symptoms of depression.


Assuntos
Adaptação Psicológica , Depressão/etiologia , Síndrome do Ovário Policístico/complicações , Qualidade de Vida/psicologia , Acne Vulgar/etiologia , Acne Vulgar/psicologia , Adolescente , Comportamento do Adolescente/psicologia , Depressão/psicologia , Feminino , Hirsutismo/etiologia , Hirsutismo/psicologia , Humanos , Síndrome do Ovário Policístico/psicologia , Sudeste dos Estados Unidos , Inquéritos e Questionários , Aumento de Peso
3.
Res Nurs Health ; 39(5): 337-46, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27305338

RESUMO

Teams of unlicensed personnel and registered nurses have provided hospital-based nursing care for decades. Although ineffective teamwork has been associated with poor patient outcomes, little is known of the perspectives of nursing assistive personnel (NAP). The purpose of this study was to gain insights into the perceptions of NAP and professional registered nurses (RNs) on teamwork in acute care. In a qualitative descriptive approach in a metropolitan hospital in the southeastern United States, 33 NAP participated in audio-recorded focus group sessions, and 18 RNs provided responses to open-ended electronic survey questions. Findings were examined in relation to previously identified coordinating mechanisms of teamwork: shared mental models, closed-loop communication, and mutual trust. None of the mechanisms was strongly represented in these data. In contrast to RNs' mental models, NAP perceptions of teamwork included the centrality of holistic caring to the NAP role, functional teams as NAP-only teams, NAPs and RNs working in parallel spheres rather than together, and team coordination in silos. Closed-loop communication was less common than one-way requests. Mutual trust was desired, but RNs' delegation of tasks conveyed to NAP a lack of value and respect for the NAP role, while RNs perceived a professional obligation to delegate care to ensure quality of care amid changing patient priorities. Further empirical research into NAP practice is needed to enhance understanding of teamwork issues and direct effective interventions to improve work environments and ultimately patient outcomes. © 2016 Wiley Periodicals, Inc.


Assuntos
Atitude do Pessoal de Saúde , Comportamento Cooperativo , Enfermeiras e Enfermeiros/psicologia , Assistentes de Enfermagem/psicologia , Comunicação , Grupos Focais , Humanos , Cultura Organizacional , Pesquisa Qualitativa , Sudeste dos Estados Unidos , Inquéritos e Questionários
4.
J Nurs Educ ; 54(4): 201-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25826760

RESUMO

BACKGROUND: Persistently high medical error rates, caregiver dissatisfaction, and compromised patient safety often result from poorly coordinated, increasingly complex health care. Barriers to interprofessional health professions education persist despite the urgent calls for improved quality and safety. Investigators explored the effects of a problem-based learning (PBL) strategy between prelicensure doctorate of pharmacy (PharmD) and baccalaureate nursing (BSN) students. METHOD: A descriptive design was used to compare the learning gains and satisfaction with a PBL hybrid approach for BSN and PharmD prelicensure student groups over three academic terms. RESULTS: Consistent with earlier works, content-based learning gains and student satisfaction were not significantly different between groups. Narrative data provide insight into perceived benefits, barriers, and perspectives of participating students and facilitators. CONCLUSION: Attributes of this pedagogical approach provide opportunity for prelicensure students to explore professional interdependence while adequately mastering fact-based content.


Assuntos
Bacharelado em Enfermagem/métodos , Educação de Pós-Graduação em Farmácia/métodos , Aprendizagem Baseada em Problemas , Licenciamento
5.
J Nurs Educ ; 50(1): 7-13, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21053861

RESUMO

Successful nurses function effectively with adaptability, improvability, and interconnectedness, and can see emerging and unpredictable complex problems. Preparing new nurses for complexity requires a significant change in prevalent but dated nursing education models for rising graduates. The science of complexity coupled with problem-based learning and peer review contributes a feasible framework for a constructivist learning environment to examine real-time systems data; explore uncertainty, inherent patterns, and ambiguity; and develop skills for unstructured problem solving. This article describes a pilot study of a problem-based learning strategy guided by principles of complexity science in a community clinical nursing course. Thirty-five senior nursing students participated during a 3-year period. Assessments included peer review, a final project paper, reflection, and a satisfaction survey. Results were higher than expected levels of student satisfaction, increased breadth and analysis of complex data, acknowledgment of community as complex adaptive systems, and overall higher level thinking skills than in previous years.


Assuntos
Enfermagem em Saúde Comunitária/educação , Bacharelado em Enfermagem/organização & administração , Dinâmica não Linear , Aprendizagem Baseada em Problemas/organização & administração , Estudantes de Enfermagem/psicologia , Teoria de Sistemas , Atitude do Pessoal de Saúde , Competência Clínica , Currículo , Processos Grupais , Humanos , Relações Interprofissionais , Modelos Educacionais , Pesquisa em Educação em Enfermagem , Revisão dos Cuidados de Saúde por Pares , Filosofia em Enfermagem , Projetos Piloto , Avaliação de Programas e Projetos de Saúde , Pensamento
6.
J Nurs Scholarsh ; 42(1): 83-91, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20487190

RESUMO

PURPOSE: To explain how baccalaureate-prepared acute care nurses understand, adapt to, and negotiate challenge and change in acute care settings in the context of social and structural features and consequently develop career persistence there. DESIGN: Grounded theory method based on the research of Strauss and Corbin. METHODS: A research team conducted open-ended interviews with a theoretic sample of 19 new and experienced baccalaureate-prepared (BSN) nurses in the southeast United States during 2007 and 2008 until saturation was achieved. Interviews were audiotaped and transcribed verbatim. Constant comparative method was used to analyze data to three increasingly abstract levels culminating in theory emergence. A diagram was developed to better understand relationships and processes. FINDINGS: A central category, building professional resilience, emerged as the central social process with three core processes of verifying fit, stage setting, and optimizing the environment contributing to career persistence in acute care. Core processes include skills and practices nurses have learned to negotiate changing acute care environments while sustaining patient advocacy. Definitions, properties, and dimensions of each were established. CONCLUSIONS: The study offers a systematic framework for understanding and promoting career persistence for acute care nurses. Findings broaden theories of resilience to the unique settings of acute care nursing and further extend theoretical understanding of the nursing shortage and market issues of supply and demand. CLINICAL RELEVANCE: A middle range theory of professional resilience and career persistence makes visible skills and practices acute-care nurses use to weather continuous change and challenge in health care. Teachable practices can be integrated into nursing education and staff development to improve professional career longevity of experienced nurses at the bedside.


Assuntos
Esgotamento Profissional/prevenção & controle , Bacharelado em Enfermagem , Recursos Humanos de Enfermagem Hospitalar , Gestão de Recursos Humanos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Recursos Humanos de Enfermagem Hospitalar/educação , Recursos Humanos de Enfermagem Hospitalar/psicologia , Recursos Humanos de Enfermagem Hospitalar/provisão & distribuição , Reorganização de Recursos Humanos , Resiliência Psicológica , Sudeste dos Estados Unidos , Desenvolvimento de Pessoal
7.
Nurs Educ Perspect ; 29(2): 80-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18459622

RESUMO

New nurses typically begin their practice in acute care settings in hospitals, where their work is characterized by time constraints, high safety risks for patients, and layers of complexity and difficult problems. Retention of experienced nurses is an issue central to patient safety. The purpose of this qualitative study was to explore the nature of professional resilience in new baccalaureate-prepared nurses in acute care settings and to extrapolate pedagogical strategies that can be developed to support resilience and career longevity. Findings revealed a common process of evolving resilience among participants. New nurses spend a significant amount of time learning their place in the social structure. With positive experiences, they begin to feel more competent with skills and relationships and become increasingly aware of discrepancies between their ideas of professional nursing and their actual experiences in the work setting. The risk of new nurses leaving their practice is constantly present during these struggles. Acceptable compromises yield a reconciliation of the current crisis, typically occurring long after formal precepting has ended. Personal growth is evident by the evolving clarity of professional identity, an edifying sense of purpose, and energy resources to move forward. For new nurses, professional resilience yields the capacity for self-protection, risk taking, and moving forward with reflective knowledge of self.


Assuntos
Adaptação Psicológica , Bacharelado em Enfermagem , Recursos Humanos de Enfermagem Hospitalar/psicologia , Adulto , Humanos , Capacitação em Serviço , Relações Enfermeiro-Paciente , Recursos Humanos de Enfermagem Hospitalar/educação , Administração de Recursos Humanos em Hospitais , Sudeste dos Estados Unidos
8.
Cell Transplant ; 16(2): 101-15, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17474292

RESUMO

Human stem cells, progenitor cells, and cell lines have been derived from embryonic, fetal, and adult sources in the search for graft tissue suitable for the treatment of CNS disorders. An increasing number of experimental studies have shown that grafts from several sources survive, differentiate into distinct cell types, and exert positive functional effects in experimental animal models, but little attention has been given to developing cells under conditions of good manufacturing practice (GMP) that can be scaled up for mass treatment. The capacity for continued division of stem cells in culture offers the opportunity to expand their production to meet the widespread clinical demands posed by neurodegenerative diseases. However, maintaining stem cell division in culture long term, while ensuring differentiation after transplantation, requires genetic and/ or oncogenetic manipulations, which may affect the genetic stability and in vivo survival of cells. This review outlines the stages, selection criteria, problems, and ultimately the successes arising in the development of conditionally immortal clinical grade stem cell lines, which divide in vitro, differentiate in vivo, and exert positive functional effects. These processes are specifically exemplified by the murine MHP36 cell line, conditionally immortalized by a temperature-sensitive mutant of the SV40 large T antigen, and cell lines transfected with the c-myc protein fused with a mutated estrogen receptor (c-mycERTAM), regulated by a tamoxifen metabolite, but the issues raised are common to all routes for the development of effective clinical grade cells.


Assuntos
Transplante de Células-Tronco/métodos , Células-Tronco/citologia , Células-Tronco/metabolismo , Animais , Divisão Celular , Humanos , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Receptores de Estrogênio/metabolismo , Cicatrização
9.
Exp Neurol ; 199(1): 143-55, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16464451

RESUMO

Transplantation of neural stem cells into the brain is a novel approach to the treatment of chronic stroke disability. For clinical application, safety and efficacy of defined, stable cell lines produced under GMP conditions are required. To this end, a human neural stem cell line, CTX0E03, was derived from human somatic stem cells following genetic modification with a conditional immortalizing gene, c-mycER(TAM). This transgene generates a fusion protein that stimulates cell proliferation in the presence of a synthetic drug 4-hydroxy-tamoxifen (4-OHT). The cell line is clonal, expands rapidly in culture (doubling time 50-60 h) and has a normal human karyotype (46 XY). In the absence of growth factors and 4-OHT, the cells undergo growth arrest and differentiate into neurons and astrocytes. Transplantation of CTX0E03 in a rat model of stroke (MCAo) caused statistically significant improvements in both sensorimotor function and gross motor asymmetry at 6-12 weeks post-grafting. In addition, cell migration and long-term survival in vivo were not associated with significant cell proliferation. These data indicate that CTX0E03 has the appropriate biological and manufacturing characteristics necessary for development as a therapeutic cell line.


Assuntos
Córtex Cerebral/citologia , Infarto da Artéria Cerebral Média/cirurgia , Células Neuroepiteliais/fisiologia , Transplante de Células-Tronco , Células-Tronco/fisiologia , Análise de Variância , Animais , Comportamento Animal , Diferenciação Celular/fisiologia , Movimento Celular , Córtex Cerebral/embriologia , Células Clonais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feto , Humanos , Hidroxitestosteronas/farmacologia , Masculino , Atividade Motora/fisiologia , Células Neuroepiteliais/citologia , RNA Mensageiro/biossíntese , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Transplante de Células-Tronco/métodos , Telomerase/efeitos dos fármacos , Telomerase/metabolismo , Fatores de Tempo , Transdução Genética/métodos
10.
Brain Res ; 1063(2): 140-50, 2005 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-16289485

RESUMO

The therapeutic potential of neural stem cell transplantation has been well demonstrated in many models of focal brain damage. However, few studies have sought to determine whether neural stem cells are therapeutic in models of diffuse brain injury, such as observed in Alzheimer's disease and global ischaemia. The present study investigated the effects of transplanted MHP36 neural stem cells on the extent of ischaemic damage in a mouse model of global ischaemia and the effects of the immunosuppressive agent cyclosporin A (CsA). C57Bl/6J mice received an intrastriatal graft of MHP36 neural stem cells 3 days after selective neuronal damage had been induced by global ischaemia. The experimental group was subdivided into CsA or saline controls. We discovered that grafts of MHP36 neural stem cells were able to differentiate into neurons and reduce the extent of ischaemic neuronal damage. This reduction was particularly apparent at 4 week post-transplantation and is independent of CsA immunosuppression. MHP36 cells survived robustly in host ischaemic brain and migrated away from the injection tract towards the caudate nucleus and corpus callosum. Although MHP36 grafts were associated with an acute inflammatory response from reactive astrocytes and microglia at 1 week post-transplantation, this decreased markedly by 4 weeks post-transplantation even in the absence of CsA immunosuppression. This is the first study showing a therapeutic benefit of neural stem cells in a highly diffuse brain injury, further highlighting the possibilities of stem cell transplantation for all types of neurodegenerative disease.


Assuntos
Isquemia Encefálica/patologia , Isquemia Encefálica/terapia , Neurônios/citologia , Transplante de Células-Tronco , Animais , Astrócitos/imunologia , Astrócitos/patologia , Isquemia Encefálica/imunologia , Diferenciação Celular , Movimento Celular , Células Cultivadas , Modelos Animais de Doenças , Encefalite/imunologia , Encefalite/patologia , Encefalite/terapia , Sobrevivência de Enxerto/imunologia , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/imunologia , Microglia/patologia , Células-Tronco/citologia
11.
Curr Alzheimer Res ; 2(1): 79-95, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15977991

RESUMO

It has long been recognised that Alzheimer's disease (AD) patients present an irreversible decline of cognitive functions as consequence of cell deterioration in the forebrain cholinergic projection system (FCPS), particularly, in a structure called nucleus basalis of Meynert (nbM). The reduction of the number of cholinergic cells in the FCPS disrupts not just its functions and direct connexions but also the modulation of other systems causing interference in several aspects of behavioural performance including arousal, attention, learning and emotion. It is also common knowledge that AD is an untreatable degenerative disease with very few temporary and palliative drug therapies. Neural stem cell (NSC) grafts present a potential and innovative strategy for the treatment of many disorders of the central nervous system including AD, with the possibility of providing a more permanent remedy than present drug treatments. After grafting, these cells have the capacity to migrate to lesioned regions of the brain and differentiate into the necessary type of cells that are lacking in the diseased brain, supplying it with the cell population needed to promote recovery. The present article aims to review the main aspects of Alzheimer's disease and to explore the use of neural stem cells grafts as alternative treatment for the consequent functional deterioration.


Assuntos
Doença de Alzheimer/terapia , Neurônios/transplante , Envelhecimento/fisiologia , Doença de Alzheimer/enzimologia , Doença de Alzheimer/fisiopatologia , Animais , Transplante de Tecido Encefálico/métodos , Colina O-Acetiltransferase/metabolismo , Modelos Animais de Doenças , Humanos , Fator de Crescimento Neural/uso terapêutico , Vias Neurais/fisiopatologia , Ratos , Transplante de Células-Tronco/métodos
12.
J Nurs Educ ; 44(12): 548-54, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16402737

RESUMO

New nurses seem unable to find a means of flourishing professionally in acute care practice and, consequently, exit far earlier than expected. Worldviews of baccalaureate students have changed from previous generations; yet, the approaches to nursing education remain essentially the same. Just as clinical settings benefit from nursing theory as the basis for nursing practice and scientific inquiry, the science of nursing education would benefit from nursing theory as a basis for guiding educational practice. Parse's human science theory, the Human Becoming School of Thought, is a fitting theoretical framework for a model of teaching-learning for undergraduate baccalaureate nursing education. In addition, as a theory of dynamic relational synchrony, Parse's work provides an appropriate framework with which to promote professional resilience and career longevity by purposefully engaging students within student-faculty dyads to explore personal meanings and philosophies of caring, and to create strong professional identities.


Assuntos
Adaptação Psicológica , Bacharelado em Enfermagem/organização & administração , Desenvolvimento Humano , Modelos Educacionais , Modelos de Enfermagem , Competência Profissional/normas , Atitude do Pessoal de Saúde , Mobilidade Ocupacional , Empatia , Docentes de Enfermagem , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Relações Interprofissionais , Mentores/psicologia , Modelos Psicológicos , Pesquisa em Educação em Enfermagem , Filosofia em Enfermagem , Aprendizagem Baseada em Problemas , Psicologia Educacional , Identificação Social , Socialização , Estudantes de Enfermagem/psicologia , Pensamento
13.
Methods Mol Med ; 104: 89-104, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15454666

RESUMO

Stem cell lines have been and are being developed to treat damage in the central nervous system after stroke. Stem cells are able to migrate to areas of damage and to differentiate into neurons and glia. Grafts of murine stem cells have been shown to promote recovery from behavioral dysfunction after stroke. We have developed protocols to optimize behavioral testing, animal recovery, and stem cell delivery after middle cerebral artery occlusion. In this chapter we discuss study protocols aimed at integrating in vitro preparation of cells, small animal surgery, behavioral testing batteries, and histological analysis.


Assuntos
Infarto da Artéria Cerebral Média/terapia , Transplante de Células-Tronco , Animais , Comportamento Animal , Linhagem Celular , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/psicologia , Masculino , Células-Tronco Multipotentes/transplante , Ratos , Ratos Sprague-Dawley
14.
Brain Res Dev Brain Res ; 151(1-2): 13-23, 2004 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-15246688

RESUMO

Neural stem cells (NSCs) are believed to repair brain damage primarily through cell replacement: i.e., the ability to regenerate lost neurons and glia in a site-specific fashion. The neural stem cell line, MHP36, has been shown to have this capacity, but we have little idea of the molecular mechanisms that control the differentiation of such cells during brain repair. In this study we show that an early event in the differentiation of MHP36 cells, both in vivo and in vitro, is the loss of expression of the intermediate filament protein, nestin. We use a co-culture assay to show that loss of nestin is fast, being detectable after just 1 h and complete in 4 h, and is controlled by proteasome degradation rather than down-regulation of de novo nestin synthesis. We also show that nestin loss is regulated by Notch, and mediated by cell contact.


Assuntos
Acetilcisteína/análogos & derivados , Cisteína Endopeptidases/metabolismo , Proteínas de Filamentos Intermediários/metabolismo , Proteínas de Membrana/fisiologia , Complexos Multienzimáticos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Transdução de Sinais/fisiologia , Células-Tronco/metabolismo , Acetilcisteína/farmacologia , Animais , Contagem de Células/métodos , Diferenciação Celular/fisiologia , Linhagem Celular , Células Cultivadas , Córtex Cerebral/citologia , Técnicas de Cocultura/métodos , Cricetinae , Cricetulus , Inibidores de Cisteína Proteinase/farmacologia , Embrião de Mamíferos , Corantes Fluorescentes , Regulação da Expressão Gênica/fisiologia , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas de Fluorescência Verde , Hipocampo/metabolismo , Imuno-Histoquímica/métodos , Proteínas de Filamentos Intermediários/genética , Proteínas Luminescentes/metabolismo , Masculino , Camundongos , Proteínas do Tecido Nervoso/genética , Nestina , Neuroglia/metabolismo , Compostos Orgânicos , Fosfopiruvato Hidratase/metabolismo , Complexo de Endopeptidases do Proteassoma , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-Dawley , Receptores Notch , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Transplante de Células-Tronco/métodos , Temperatura , Fatores de Tempo , Transfecção/métodos
15.
Exp Neurol ; 179(2): 127-38, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12618119

RESUMO

Regional depositions of calcium within the basal ganglia, cortex, cerebellum, and white matter and at perivascular sites have been observed in several pathological conditions. These generally indicate signs of ongoing apoptosis or necrotic processes, whereby the activation of glutamate receptors causes a rise in intracellular calcium levels leading to mineralization of neurons, and ultimately to cell death. The selective degeneration of cholinergic neurons in the basal forebrain is a major neuropathological component of Alzheimer's disease, and may result in abnormal deposition of calcium. In experimental models, selective lesions of the basal forebrain can be induced by intraparenchymal infusions of excito- or immunotoxins targeting cholinergic neurons. Excitotoxic lesions are often accompanied by calcium deposition within affected areas. In a previous study we also noted the presence of unusual deposition in areas close to the site of injections following unilateral S-AMPA-induced lesions of the basal forebrain (T. Perry, H. Hodges, and J. A. Gray, 2001, Brain Res. Bull. 54, 29-48). In this paper, we have characterized these deposits histologically and evaluated the microglial (CD11b) and astrocytic (GFAP) responses at 8 and 16 weeks following lesioning of the nucleus basalis magnocellularis with S-AMPA. The resulting deposits were heterogeneous in morphology and composed primarily of calcium. Small granular deposits were detected around blood vessels, whereas larger calcospherites were situated within the parenchyma. These deposits were more widely dispersed at 16 weeks postlesioning, affected neighboring nuclei, and displayed a progressive increase in size and frequency of occurrence. However, calcification within these regions was differentially associated with microglial and astrocytic reactivity at the two time points. Both microglial and astrocytic responses were pronounced at 8 weeks, whereas at 16 weeks, astrocytic reactivity prevailed and the microglial response was markedly attenuated. Importantly, the pattern of reactivity for microglia detected at 8 weeks was specifically localized to vulnerable nucleated areas prior to their substantial accumulation of calcium deposits, which was clearly evident by 16 weeks. We suggest that the initial microglial response could be used as a selective predictor of tissue necrosis and subsequent calcification, and that astrocytes, which form a glial scar in the affected tissues, may contribute toward the buildup of calcium deposits. The functional relevance of these findings is discussed.


Assuntos
Calcinose/induzido quimicamente , Neuroglia/efeitos dos fármacos , Neurotoxinas/toxicidade , Prosencéfalo/efeitos dos fármacos , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/toxicidade , Animais , Núcleo Basal de Meynert/efeitos dos fármacos , Núcleo Basal de Meynert/patologia , Calcinose/patologia , Progressão da Doença , Imuno-Histoquímica , Masculino , Microglia/efeitos dos fármacos , Microglia/patologia , Microinjeções , Neuroglia/patologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Neurotoxinas/administração & dosagem , Prosencéfalo/patologia , Ratos , Ratos Sprague-Dawley , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/administração & dosagem
16.
Neuroreport ; 14(1): 39-42, 2003 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-12544827

RESUMO

Searching for valid control grafts, we assessed the performance of rats subjected to middle cerebral artery occlusion (MCAO) and grafted with freeze-thawed dead stem cells into sites previously used for active grafts (ipsilateral and contralateral striatum and ventricle) on bilateral asymmetry and water maze tests. We expected to find that sham grafted groups had impairments equivalent to those of MCAO-only controls, relative to intact controls. This proved to be the case for contralateral and intraventricular grafts, and for asymmetry in rats with ipsilateral grafts. However, spatial learning was substantially impaired and lesion volume was increased by 55% with ipsilateral dead cell grafts. Exacerbation of stroke effects indicates potential hazards in the use of dead cells for sham grafts.


Assuntos
Infarto da Artéria Cerebral Média/cirurgia , Deficiências da Aprendizagem/etiologia , Transplante de Células-Tronco/efeitos adversos , Animais , Morte Celular , Linhagem Celular/transplante , Ventrículos Cerebrais , Corpo Estriado , Dominância Cerebral , Congelamento , Inflamação , Masculino , Aprendizagem em Labirinto , Desempenho Psicomotor , Ratos , Ratos Sprague-Dawley , Projetos de Pesquisa , Transplante Heterotópico
17.
Brain Res ; 958(1): 70-82, 2002 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-12468031

RESUMO

The use of progenitors and stem cells for neural grafting is promising, as these not only have the potential to be maintained in vitro until use, but may also prove less likely to evoke an immunogenic response in the host, when compared to primary (fetal) grafts. We investigated whether the short-term survival of a grafted conditionally immortalised murine neuroepithelial stem cell line (MHP36) (2 weeks post-implantation, 4 weeks post-ischaemia) is influenced by: (i) immunosuppression (cyclosporin A (CSA) vs. no CSA), (ii) the local (intact vs. lesioned hemisphere), or (iii) global (lesioned vs. sham) brain environment. MHP36 cells were transplanted ipsi- and contralateral to the lesion in rats with middle cerebral artery occlusion (MCAo) or sham controls. Animals were either administered CSA or received no immunosuppressive treatment. A proliferation assay of lymphocytes dissociated from cervical lymph nodes, grading of the survival of the grafted cells, and histological evaluation of the immune response revealed no significant difference between animals treated with or without CSA. There was no difference in survival or immunological response to cells grafted ipsi- or contralateral to the lesion. Although a local upregulation of immunological markers (MHC class I, MHC class II, CD45, CD11b) was detected around the injection site and the ischaemic lesion, these were not specifically upregulated in response to transplanted cells. These results provide evidence for the low immunogenic properties of MHP36 cells during the initial period following implantation, known to be associated with an acute host immune response and ensuing graft rejection.


Assuntos
Linhagem Celular Transformada/transplante , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Infarto da Artéria Cerebral Média/terapia , Neurônios/transplante , Transplante de Células-Tronco , Acidente Vascular Cerebral/terapia , Animais , Biomarcadores , Transplante de Tecido Encefálico , Linhagem Celular Transformada/imunologia , Ciclosporina/farmacologia , Modelos Animais de Doenças , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Imuno-Histoquímica , Terapia de Imunossupressão , Imunossupressores/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Neurônios/imunologia , Ratos , Ratos Sprague-Dawley
18.
Neuroimage ; 17(2): 803-11, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12377155

RESUMO

The ability to track stem cell transplants in the brain by in vivo neuroimaging will undoubtedly aid our understanding of how these cells mediate functional recovery after neural transplantation. One major challenge for the development and refinement of stem cell transplantation is to map the spatial distribution and rate of migration in situ. Here we report a method for tracking transplanted stem cells in the ischemia-damaged rat hippocampus by magnetic resonance imaging (MRI). Before transplantation, stem cells were labeled in vitro either with a novel bifunctional contrast agent, gadolinium rhodamine dextran (GRID), identifiable by both MRI and fluorescence microscopy, or with PKH26, visible exclusively under fluorescence microscopy. At different time points following engraftment, the brains were evaluated by both histology and ex vivo MR imaging. Transplanted stem cells were identified by MRI only if prelabeled with GRID, whereas fluorescence microscopy detected transplanted cells using either label. The distribution of GRID-labeled stem cells identified by MRI corresponded to those detected using fluorescence microscopy. These results demonstrate that GRID-enhanced MRI can reliably identify transplanted stem cells and their migration in the brain.


Assuntos
Encéfalo/citologia , Movimento Celular/fisiologia , Imageamento por Ressonância Magnética/métodos , Transplante de Células-Tronco/métodos , Animais , Astrócitos/fisiologia , Isquemia Encefálica/patologia , Diferenciação Celular/fisiologia , Linhagem Celular , Circulação Cerebrovascular , Técnicas de Cocultura , Meios de Contraste , Cricetinae , Dextranos , Corantes Fluorescentes , Gadolínio , Imuno-Histoquímica , Indicadores e Reagentes , Microscopia de Fluorescência , Neurônios/fisiologia , Ratos , Ratos Wistar , Rodaminas
19.
Stroke ; 33(9): 2270-8, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12215598

RESUMO

BACKGROUND AND PURPOSE: Findings that MHP36 stem cells grafted into intact parenchyma contralateral to the lesion induced by middle cerebral artery occlusion promoted recovery from stroke deficits led us to investigate whether implantation site of stem cells affects the functional efficacy of MHP36 grafts. METHODS: MHP36 cells (200 000/8 microL) were implanted in the left (n=8) or right (n=9) parenchyma or infused into the right ventricle (intraventricular; n=7) 2 to 3 weeks after stroke induced by 60 minutes of intraluminal right middle cerebral artery occlusion. Additionally, intact (n=11) and stroke (n=7) control groups were tested for 14 weeks in bilateral asymmetry, rotation bias, and spatial learning tasks before histological investigation of cell distribution and differentiation. RESULTS: Rats with left and right parenchymal grafts showed reduced bilateral asymmetry but no improvement in spatial learning. Conversely, spatial learning improved in rats with intraventricular grafts, but marked asymmetry persisted. No grafted group showed reduced amphetamine-induced rotation bias or reduced lesion volume relative to stroke controls. In all grafted groups, cells occupied both sides of the brain. A third of cells grafted in the striatum crossed the midline to occupy homologous regions in intact and lesioned hemispheres and differentiated into site-appropriate phenotypes. CONCLUSIONS: After stroke, both the intact and lesioned hemispheres attract grafted stem cells, suggesting repair processes that utilize cells both for local repair and to augment plastic changes in contralateral motor pathways. However, differential effects of parenchymal and intraventricular grafts suggest that different mechanisms are implicated in recovery from cognitive and sensorimotor deficits induced by stroke.


Assuntos
Transplante de Células-Tronco , Acidente Vascular Cerebral/terapia , Animais , Antígenos de Diferenciação/biossíntese , Comportamento Animal , Contagem de Células , Diferenciação Celular , Linhagem Celular , Ventrículos Cerebrais , Modelos Animais de Doenças , Sobrevivência de Enxerto , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/terapia , Aprendizagem em Labirinto , Atividade Motora , Neurônios/citologia , Especificidade de Órgãos , Fenótipo , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Rotação , Células-Tronco/citologia , Células-Tronco/metabolismo , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/patologia , Resultado do Tratamento
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