Schnell L, Fearn S, Schwab M E, Perry V H, Anthony D C
CNS Inflammation Group, School of Biological Sciences, University of Southampton, United Kingdom.
J Neuropathol Exp Neurol. 1999 Mar;58(3):245-54. doi: 10.1097/00005072-199903000-00004.
Different compartments in the central nervous system mount distinct inflammatory responses. The meninges and choroid plexus respond to pro-inflammatory stimuli in a manner reminiscent of a peripheral inflammatory response, whereas the brain parenchyma is refractory. Trauma-induced lesions in brain and in spinal cord are associated with leukocyte infiltration, blood-brain barrier (BBB) breakdown, and secondary tissue destruction. Unexpectedly, these phenomena are generally more pronounced in the parenchyma of the spinal cord than in the parenchyma of the brain. To investigate whether these differences between brain and spinal cord can be attributed, at least in part, to differing sensitivities to proinflammatory cytokines, we stereotactically injected recombinant rat (rr) TNFalpha or rrIL-1beta into the striatum or the spinal cord of Wistar rats. In the brain, the injection of rrTNFalpha failed to evoke BBB breakdown or leukocyte recruitment, whereas in the spinal cord injection of TNFalpha resulted in marked BBB breakdown and leukocyte recruitment. Similarly, the injection of rrIL-1beta into the brain parenchyma failed to induce BBB breakdown and gave rise to only minimal neutrophil recruitment, whereas the injection of rrIL-1beta into the spinal cord induced significant BBB breakdown and recruitment of neutrophils and lymphocytes. Thus, using a minimally invasive injection technique, equivalent in both circumstances, we have shown that there are marked differences in the inflammatory response between the brain parenchyma and spinal cord parenchyma. This observation has important implications for the treatment of spinal cord injuries.
中枢神经系统的不同区域会产生不同的炎症反应。脑膜和脉络丛对促炎刺激的反应方式类似于外周炎症反应,而脑实质则具有抗性。脑和脊髓中的创伤性损伤与白细胞浸润、血脑屏障(BBB)破坏以及继发性组织损伤有关。出乎意料的是,这些现象在脊髓实质中通常比在脑实质中更为明显。为了研究脑和脊髓之间的这些差异是否至少部分归因于对促炎细胞因子的不同敏感性,我们通过立体定向将重组大鼠(rr)TNFα或rrIL-1β注射到Wistar大鼠的纹状体或脊髓中。在脑中,注射rrTNFα未能引起血脑屏障破坏或白细胞募集,而在脊髓中注射TNFα则导致明显的血脑屏障破坏和白细胞募集。同样,向脑实质注射rrIL-1β未能诱导血脑屏障破坏,仅引起极少的中性粒细胞募集,而向脊髓注射rrIL-1β则诱导了明显的血脑屏障破坏以及中性粒细胞和淋巴细胞的募集。因此,使用在两种情况下都相同的微创注射技术,我们已经表明脑实质和脊髓实质之间的炎症反应存在显著差异。这一观察结果对脊髓损伤的治疗具有重要意义。