Reis D J, Golanov E V, Galea E, Feinstein D L
Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York, USA.
Ann N Y Acad Sci. 1997 Dec 19;835:168-86. doi: 10.1111/j.1749-6632.1997.tb48628.x.
The brain can protect itself from ischemia and/or hypoxia by two distinct mechanisms which probably involve two separate systems of neurons in the CNS. One, which mediates a reflexive neurogenic neuroprotection, emanates from oxygen-sensitive sympathoexcitatory reticulospinal neurons of the RVLM. These cells, excited within seconds by reduction in blood flow or oxygen, initiate the systemic vascular components of the oxygen conserving (diving) reflex. They profoundly increase rCBF without changing rCGU and, hence, rapidly and efficiently provide the brain with oxygen. Upon cessation of the stimulus the systemic and cerebrovascular adjustments return to normal. The system mediating reflex protection projects via as-yet-undefined projections from RVLM to upper brainstem and/or thalamus to engage a small population of neurons in the cortex which appear to be dedicated to transducing a neuronal signal into vasodilation. It also appears to relay the central neurogenic vasodilation elicited from other brain regions, including excitation of axons innervating the FN. This mode of protection would be initiated under conditions of global ischemia and/or hypoxemia because the signal is detected by medullary neurons. The second neuroprotective system is represented in intrinsic neurons of the cerebellar FN and mediates a conditioned central neurogenic neuroprotection. The response can be initiated by excitation of intrinsic neurons of the FN and does not appear dependent upon RVLM. The pathways and transmitters that mediate the effect are unknown. The neuroprotection afforded by this network is long-lasting, persisting for almost two weeks, and is associated with reduced excitability of cortical neurons and reduced immunoreactivity of cerebral microvessels. This mode of neuroprotection, moreover, is not restricted to focal ischemia, as we have demonstrated that it also protects the brain against global ischemia and excitotoxic cell death. That the brain may have neuronal systems dedicated to protecting itself from injury, at first appearing to be a novel concept, is, upon reflection, not surprising since the brain is not injured in naturalistic behaviors characterized by very low levels of rCBF, diving and hibernation. An understanding of the pathways, transmitters, and molecules engaged in such protection may provide new insights into novel therapies for a range of disorders characterized by neuronal death.
大脑可通过两种不同机制保护自身免受缺血和/或缺氧影响，这两种机制可能涉及中枢神经系统中两个独立的神经元系统。一种机制介导反射性神经源性神经保护，源自延髓头端腹外侧区（RVLM）对氧敏感的交感兴奋网状脊髓神经元。这些细胞在血流或氧气减少后数秒内被激活，启动保氧（潜水）反射的全身血管成分。它们能显著增加局部脑血流量（rCBF）而不改变局部脑葡萄糖利用率（rCGU），从而迅速有效地为大脑提供氧气。刺激停止后，全身和脑血管调节恢复正常。介导反射性保护的系统通过从RVLM到上脑干和/或丘脑的尚未明确的投射，使一小群皮层神经元参与其中，这些神经元似乎专门负责将神经元信号转化为血管舒张。它似乎还能传递从其他脑区引发的中枢神经源性血管舒张，包括支配面神经核（FN）的轴突兴奋。这种保护模式将在全脑缺血和/或低氧血症情况下启动，因为该信号由延髓神经元检测到。第二种神经保护系统存在于小脑FN的内在神经元中，介导条件性中枢神经源性神经保护。该反应可由FN内在神经元的兴奋引发，似乎不依赖于RVLM。介导该效应的途径和递质尚不清楚。该网络提供的神经保护作用持久，持续近两周，与皮层神经元兴奋性降低和脑微血管免疫反应性降低有关。此外，这种神经保护模式不仅限于局灶性缺血，正如我们所证明的，它还能保护大脑免受全脑缺血和兴奋性毒性细胞死亡的影响。大脑可能拥有专门保护自身免受损伤的神经元系统，这一概念乍一看似乎很新颖，但仔细想想并不奇怪，因为在以极低rCBF为特征的自然行为（如潜水和冬眠）中，大脑并未受到损伤。对参与这种保护的途径、递质和分子的理解可能为一系列以神经元死亡为特征的疾病的新疗法提供新的见解。
