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In JoVE (2)
- Estratégias para Estudo da neuroproteção de frio pré-condicionamento
- Modelagem Neural Sinalização Imune de migrânea episódica e crônica Usando a depressão alastrante In Vitro
Other Publications (2)
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Articles by Heidi M. Mitchell in JoVE
Estratégias para Estudo da neuroproteção de frio pré-condicionamento
Heidi M. Mitchell, David M. White, Richard P. Kraig
Department of Neurology, The University of Chicago Medical Center
Procuramos definir a sinalização neural imunológico responsável por pré-condicionamento frio, como meios para identificar novos alvos para o desenvolvimento de terapias para proteger o cérebro antes do início da lesão. Apresentamos estratégias para esse trabalho que exigem sistemas biológicos, manipulações experimentais mais capacidades técnicas que são altamente reprodutíveis e sensíveis.
Modelagem Neural Sinalização Imune de migrânea episódica e crônica Usando a depressão alastrante In Vitro
Aya D. Pusic*1, Yelena Y. Grinberg*1, Heidi M. Mitchell2, Richard P. Kraig1
1Department of Neurology and Committee on Neurobiology, The University of Chicago Medical Center, 2Department of Neurology, The University of Chicago Medical Center
Enxaqueca e sua transformação para enxaqueca crônica são um fardo imenso de saúde que precisam de opções de tratamento melhoraram. Procuramos definir como sinalização imune neural modula a suscetibilidade à enxaqueca, modelada
Other articles by Heidi M. Mitchell on PubMed
Dose-response : a Publication of International Hormesis Society. 2010 | Pubmed ID: 21191481
Environmental enrichment, i.e., increased intellectual, social, and physical activity makes brain more resilient to subsequent neurological disease. The mechanisms for this effect remain incompletely defined, but evidence shows tumor necrosis factor-alpha (TNF-α) is involved. TNF-α, at acutely high levels, possesses the intrinsic capacity to enhance injury associated with neurological disease. Conversely, the effect of TNF-α at low-levels is nutritive over time, consistent with physiological conditioning hormesis. Evidence shows that neural activity triggers low-level pro-inflammatory signaling involving TNF-α. This low-level TNF-α signaling alters gene expression, resulting in an enhanced resilience to disease. Brain-immune signaling may become maladaptive when increased activity is chronic without sufficient periods of reduced activity necessary for nutritive adaptation. Such tonically increased activity may explain, for example, the transformation of episodic to chronic migraine with related increased susceptibility to spreading depression, the most likely underlying cause of this malady. Thus, TNF-α, whose function is to alter gene expression, and its principal cellular source, microglia, seem powerfully positioned to orchestrate hormetic immune signaling that establishes the phenotype of neurological health and disease from brain activity.
Cold Pre-conditioning Neuroprotection Depends on TNF-α and is Enhanced by Blockade of Interleukin-11
Journal of Neurochemistry. Apr, 2011 | Pubmed ID: 21070241
Cold pre-conditioning reduces subsequent brain injury in small animals but the underlying mechanisms remain undefined. As hypothermia triggers systemic macrophage tumor necrosis factor alpha (TNF-α) production and other neural pre-conditioning stimuli depend on this cytokine, we reasoned that microglia and TNF-α would be similarly involved with cold pre-conditioning neuroprotection. Also, as slice cultures closely approximate their in vivo counterpart and include quiescent microglia, we used rat hippocampal slice cultures to confirm this hypothesis. Furthermore, inflammatory cytokine gene screening with subsequent PCR and immunostaining confirmation of targeted mRNA and related protein changes showed that cold pre-conditioning triggered a significant rise in TNF-α that localized to microglia and a significant rise in interleukin (IL)-11 that localized mainly to hippocampal pyramidal neurons and, more rarely, astrocytes. Importantly, co-stimulation with cold and IL-11, an anti-inflammatory cytokine that inhibits TNF-α expression, abrogated the otherwise evident protection. Instead, cold pre-conditioning coupled with blockade of IL-11 signaling further enhanced neuroprotection from that seen with cold pre-conditioning alone. Thus, physiological activation of brain pro-inflammatory cytokine signaling, and its amplification by inhibition of coincident anti-inflammatory cytokine signaling, may be opportune targets for the development of novel therapeutics that can mimic the protection seen in cold pre-conditioning.