Complement activation in the human brain after traumatic head injury
Complement activation in the human brain after traumatic head injury
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DOI：
10.1089/08977150152725605
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发表时间：
2001-12-01
影响因子：
4.2
通讯作者：
Svensson, M
中科院分区：
文献类型：
--
作者：
Bellander, BM;Singhrao, SK;Svensson, M
基于动物实验，补体级联反应被认为参与脑挫伤后继发性脑损伤的发展。本研究的目的是检查可能参与的补体级联在人脑创伤性脑损伤后。本研究纳入了16名患者，年龄在12-77岁之间，在神经重症监护室接受创伤性脑挫伤治疗。所有患者均因顽固性颅内高压而接受额叶或颞叶切除术。分析切除的组织中与补体激活相关的成分。事故发生与手术时间间隔2-82 h。来自三名因癫痫而接受小脑切除术（包括颞叶切除术）的患者的脑组织被用作对照。我们发现补体成分C1 q，C3 b，C3 d和膜攻击复合物（MAC），C5 b-9，在紧邻的挫伤的半影区的神经元的免疫反应性增加。这些发现构成了人类大脑皮质挫伤半影区补体级联激活的组织学证据。使用原位杂交，我们还发现C3-mRNA的半影区，这表明当地的补体合成。此外，在同一区域的一些神经元中发现了内源性补体调节剂clusterin的上调。我们认为，未知化合物的碎片从受伤的神经元或髓鞘分解产物触发补体激活，包括形成C5 b-9。活化的补体成分可以刺激炎性细胞的积累和脑水肿的形成，以及通过终产物MAC具有膜破坏作用，从而成为继发性脑损伤发展中的介质。
The complement cascade has been suggested to be involved in the development of secondary brain injuries following brain contusions, based on animal experiments. The aim of the present study was to examine the possible involvement of the complement cascade following traumatic head injury in the human brain. Sixteen patients were included in this study, 12-77 years of age, treated at the neurointensive care unit for traumatic brain contusions. All of these patients were operated with frontal or temporal lobe resection due to intractable intracranial hypertension. The resected tissue was analyzed with regard to components related to complement activation. The time interval between accident and operation was 2-82 h. Brain tissue from three patients operated with hippocampectomy due to epilepsy, including temporal lobe resection, were used as controls. We found increased immunoreactivity for complement components C1q, C3b, and C3d and the membrane attack complex (MAC), C5b-9, in the immediate vicinity of neurons in the penumbra area of the contusion. These findings constitute histological evidence for activation of the complement cascade in the penumbra of cortical contusions in the human brain. Using in situ hybridization, we also found C3-mRNA in the penumbra, suggesting a local synthesis of complement. Furthermore, upregulation of the endogenous complement regulator clusterin was found in some neurons in the same area. We suggest that unknown compounds in the debris from injured neurons or myelin breakdown products trigger complement activation, including formation of C5b-9. Activated complement components may stimulate accumulation of inflammatory cells and formation of brain edema, as well as having membrane destructive effects by the end product MAC, thereby being mediators in the development of secondary brain damage.