Bauer Jan, Elger Christian E, Hans Volkmar H, Schramm Johannes, Urbach Horst, Lassmann Hans, Bien Christian G
Division of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria.
Ann Neurol. 2007 Jul;62(1):67-80. doi: 10.1002/ana.21148.
The current histopathological criteria of Rasmussen's encephalitis (RE) include the presence of T-cell-dominated inflammation, microglial activation, neuronal loss, and astrocytic activation. An in vitro study, however, suggested glutamate receptor 3 (GluR3) antibody-mediated astrocytic loss. Therefore, we investigated astrocytic apoptosis and loss in situ.
Histochemical, immunohistochemical, terminal deoxynucleotidyltransferase-mediated biotin-dUTP nick end labeling and in situ hybridization techniques were applied to paraffin sections of 20 RE cases, 6 healthy control subjects, and 6 paraneoplastic encephalomyelitis, 10 Ammon's horn sclerosis, and 5 focal cortical dysplasia cases.
Astrocytic apoptosis and subsequent loss of these cells is a specific feature of RE. Such lesions are not found in the control groups. In RE, astrocytic apoptosis and loss was present both in cortical and in white matter areas. Astrocytes in these tissues showed major histocompatibility complex class I expression. Furthermore, granzyme-B(+) lymphocytes were found in close apposition to astrocytes bordering astrocyte-deficient lesions. Granzyme-B(+) granules in these lymphocytes were polarized and faced the astrocytic membranes. No evidence was found for an antibody-mediated destruction.
We suggest a specific attack by cytotoxic T lymphocytes as a possible mechanism responsible for astrocytic degeneration in RE. The loss of astrocytes might play a role in neuronal dysfunction, seizure induction, and enhancement of neuronal cell death.
目前拉斯穆森脑炎（RE）的组织病理学标准包括以T细胞为主的炎症、小胶质细胞活化、神经元丢失和星形胶质细胞活化。然而，一项体外研究提示谷氨酸受体3（GluR3）抗体介导星形胶质细胞丢失。因此，我们对星形胶质细胞的原位凋亡和丢失情况进行了研究。
将组织化学、免疫组织化学、末端脱氧核苷酸转移酶介导的生物素-dUTP缺口末端标记法及原位杂交技术应用于20例RE患者、6例健康对照者、6例副肿瘤性脑脊髓炎患者、10例海马硬化患者及5例局灶性皮质发育不良患者的石蜡切片。
星形胶质细胞凋亡及随后这些细胞的丢失是RE的一个特异性特征。在对照组中未发现此类病变。在RE中，皮质和白质区域均存在星形胶质细胞凋亡和丢失。这些组织中的星形胶质细胞表达主要组织相容性复合体I类分子。此外，在与星形胶质细胞缺失病变相邻的星形胶质细胞旁发现了颗粒酶B（+）淋巴细胞。这些淋巴细胞中的颗粒酶B（+）颗粒呈极化状态并朝向星形胶质细胞膜。未发现抗体介导破坏的证据。
我们认为细胞毒性T淋巴细胞的特异性攻击可能是RE中星形胶质细胞变性的一种可能机制。星形胶质细胞的丢失可能在神经元功能障碍、癫痫诱导及神经元细胞死亡增加中起作用。
