Gemma Carmelina
Department of Neurosurgery and Brain Repair, USF Tampa FL, and James A. Haley VAMC, Tampa FL, USA.
Aging Dis. 2010 Dec 1;1(3):169-172.
Inflammation is by definition a protective phase of the immune response. The very first goal of inflammation is destroying and phagocytosing infected or damaged cells to avoid the spread of the pathogen or of the damage to neighboring, healthy, cells. However, we now know that during many chronic neurological disorders, inflammation and degeneration always coexist at certain time points. For example, inflammation comes first in multiple sclerosis, but degeneration follows, while in Alzheimer's or Parkinson's disease degeneration starts and inflammation is secondary. Either way these are the two pathological detectable problems. The central nervous system (CNS) has long been viewed as exempt from the effects of the immune system. The brain has physical barriers for protection, and it is now clear that cells in the nervous system respond to inflammation and injury in unique ways. In recent years, researchers have presented evidence supporting the idea that in the CNS there is an ongoing protective inflammatory mechanism, which involves macrophage, monocytes, T cells, regulatory T-cells, effector T cells and many others; these, in turn, promote repair mechanisms in the brain not only during inflammatory, and degenerative disorders but also in healthy people. This "repair mechanism" can be considered as an intrinsic part of the physiological activities of the brain. It is now well known that the microenvironment of the brain is a crucial player in determining the relative contribution of the two different outcomes. Failure of molecular and cellular mechanisms sustaining the "brain-repair programme" might be, at least in part, a cause of neurological disorders. Today, the neurotoxic and neuroprotective roles of the innate immune reactions in aging, brain injury, ischemia, autoimmune and neurodegenerative disorders of the CNS are widely investigated and highly debated research topics. Nevertheless, several issues remain to be elucidated, notably the earlier cellular events that initiate dysregulation of brain inflammatory pathways. If these inflammatory processes could be identified and harnessed, then cognitive function may be protected during aging and age-related neurodegenerative diseases through early interventions directed against the negative consequences of inflammation. This commentary highlights the major issues/opinions presented by experts on the involvement of the brain immune system in aging and age-related diseases in a special edition of the journal Aging and Disease.
从定义上讲，炎症是免疫反应的一个保护阶段。炎症的首要目标是破坏并吞噬受感染或受损的细胞，以避免病原体扩散或损伤蔓延至邻近的健康细胞。然而，我们现在知道，在许多慢性神经疾病中，炎症和退化在某些时间点总是同时存在。例如，在多发性硬化症中炎症先出现，随后是退化，而在阿尔茨海默病或帕金森病中，退化先开始，炎症是继发的。不管怎样，这都是两个可通过病理学检测到的问题。长期以来，中枢神经系统（CNS）一直被认为不受免疫系统影响。大脑有物理屏障进行保护，现在很清楚的是，神经系统中的细胞以独特的方式对炎症和损伤做出反应。近年来，研究人员提供了证据支持这样一种观点，即在中枢神经系统中存在一种持续的保护性炎症机制，其中涉及巨噬细胞、单核细胞、T细胞、调节性T细胞、效应T细胞等许多细胞；反过来，这些细胞不仅在炎症和退行性疾病期间，而且在健康人群中，都促进大脑的修复机制。这种“修复机制”可被视为大脑生理活动的一个内在组成部分。现在众所周知，大脑的微环境在决定这两种不同结果的相对作用方面起着关键作用。维持“大脑修复程序”的分子和细胞机制的失效可能至少部分是神经疾病的一个原因。如今，先天性免疫反应在中枢神经系统的衰老、脑损伤、缺血、自身免疫和神经退行性疾病中的神经毒性和神经保护作用是广泛研究且备受争议的研究课题。然而，仍有几个问题有待阐明，尤其是引发脑部炎症途径失调的早期细胞事件。如果能够识别并利用这些炎症过程，那么通过针对炎症负面后果的早期干预，认知功能在衰老和与年龄相关的神经退行性疾病期间可能会得到保护。这篇评论文章突出了该期刊《衰老与疾病》特刊中专家们提出的关于大脑免疫系统在衰老和与年龄相关疾病中的参与的主要问题/观点。
