Czigner A, Mihály A, Farkas O, Büki A, Krisztin-Péva B, Dobó E, Barzó P
Department of Anatomy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Acta Neurochir (Wien). 2007 Mar;149(3):281-9. doi: 10.1007/s00701-006-1095-8. Epub 2007 Feb 9.
The contribution of brain edema to brain swelling in cases of traumatic brain injury (TBI) remains a critical problem. We believe that inflammatory reactions may play a fundamental role in brain swelling following a head injury. Although possible roles of microglia activation and the release of mediators have been suggested, direct evidence of cellular immune reactivity in diffuse brain injury following closed head trauma is lacking. Accordingly, the objective of this study was to assess the temporal pattern of microglia activation and lymphocyte migration in an experimental model of TBI.
An impact acceleration TBI model was utilized to induce diffuse brain damage in adult Wistar rats. The animals were separated into three groups: unoperated controls, sham-operated controls and trauma group. At various times after TBI induction (5 min-24 h), rats were perfused transcardially. Sagittal brain sections were analyzed with immunohistochemical markers of CD3 to reveal the presence of T-lymphocytes, and by immunochemistry for the detection of CD11b to reveal microglia activation within the brain parenchyma.
In the control groups, scattered T-cells were found in the brain parenchyma. In the trauma group, TBI induced microglia activation and a transient biphasic T-cell infiltration of the brain parenchyma in all regions was found, beginning as early as 30 min post injury and reaching its maximum values at 45 min and 3 h after trauma induction.
These results lead us to suggest that the acute response to severe head trauma with early edema formation is likely to be associated with inflammatory events which might be triggered by activated microglia and infiltrating lymphocytes. It is difficult to overestimate the clinical significance of these observations, as the early and targeted treatment of patients with severe head injuries with immunosuppressive medication may result in a far more favorable outcome.
在创伤性脑损伤（TBI）病例中，脑水肿对脑肿胀的影响仍然是一个关键问题。我们认为炎症反应可能在头部受伤后的脑肿胀中起基本作用。尽管有人提出了小胶质细胞激活和介质释放的可能作用，但缺乏闭合性颅脑外伤后弥漫性脑损伤中细胞免疫反应性的直接证据。因此，本研究的目的是评估TBI实验模型中小胶质细胞激活和淋巴细胞迁移的时间模式。
利用撞击加速TBI模型在成年Wistar大鼠中诱导弥漫性脑损伤。将动物分为三组：未手术对照组、假手术对照组和创伤组。在TBI诱导后的不同时间（5分钟 - 24小时），经心脏灌注大鼠。用CD3免疫组化标记物分析矢状脑切片以显示T淋巴细胞的存在，并通过免疫化学检测CD11b以揭示脑实质内的小胶质细胞激活。
在对照组中，在脑实质中发现散在的T细胞。在创伤组中，发现TBI诱导小胶质细胞激活，并且在所有区域脑实质中均出现短暂的双相T细胞浸润，最早在受伤后30分钟开始，并在创伤诱导后45分钟和3小时达到最大值。
这些结果使我们认为，对伴有早期水肿形成的严重头部创伤的急性反应可能与炎症事件有关，这些炎症事件可能由活化的小胶质细胞和浸润的淋巴细胞触发。很难高估这些观察结果的临床意义，因为用免疫抑制药物对严重头部受伤患者进行早期和有针对性的治疗可能会带来更有利的结果。
