Acute splenic irradiation reduces brain injury in the rat focal ischemic stroke model.

Acute splenic irradiation reduces brain injury in the rat focal ischemic stroke model.
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急性脾辐射可减少大鼠局灶性缺血性中风模型中的脑损伤。

DOI:
10.1007/s12975-012-0206-5
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发表时间:
2012-12
影响因子:
6.9
通讯作者:
Zhang, John H.
Zhang, John H.
中科院分区:
医学1区
文献类型:
--
作者:
Ostrowski, Robert P.;Schulte, Reinhard W.;Nie, Ying;Ling, Ted;Lee, Timothy;Manaenko, Anatol;Gridley, Daila S.;Zhang, John H.

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在缺血性脑卒中前切除脾脏可消除对脑损伤的免疫反应,减少脑梗死。然而,脾切除术对脑卒中后神经保护的有效性尚未得到证实。此外,中风患者脾切除术的风险对消除脾的炎症反应造成了主要障碍。我们假设急性脾照射会消融脾细胞,从而减少中风的进展。雄性成年Sprague Dawley大鼠大脑中动脉闭塞2小时后,于脑缺血开始后3、4、6、8小时用8Gy的钴60照射脾外侧区。未经处理的对照组也进行了相同的程序,只是进行了假照射。缺血后2天或7天对大鼠实施安乐死,恢复大鼠大脑,评估脑损伤和神经炎症程度。脑卒中后3小时照射可降低脾脏重量和淋巴细胞血水平。缺血开始后3小时和4小时的脾照射分别显著减少了48小时和7天的脑梗死体积。第7天的组织学分析显示,照射4小时大鼠的小胶质细胞、浸润性T细胞和凋亡神经元计数减少。在长达4小时的时间间隔内进行的无创单剂量脾照射程序可能通过取消脾细胞到大脑的部署来提供对缺血性中风的神经保护。
Removing the spleen prior to ischemic stroke abrogates immunologic response to brain injury and reduces cerebral infarction. However, the effectiveness of splenectomy for neuroprotection after stroke has not been established. Moreover, the risks of the surgical splenectomy in stroke patients create a major obstacle to removing the spleen’s inflammatory response. We hypothesized that acute splenic irradiation will ablate splenic cells and thereby will diminish stroke progression. Male adult Sprague Dawley rats were subjected to 2-hour middle cerebral artery occlusion (MCAO), then CT scanned for spleen localization and irradiated to the lateral splenic region with 8Gy of Cobalt 60 at 3, 4, 6 or 8 hrs after start of cerebral ischemia. Untreated controls underwent the same procedures except that sham irradiation was applied. At 2 or 7 days after ischemia the rats were euthanized, and brains recovered for the assessment of brain injury and the extent of neuroinflammation. Irradiation at 3 hrs reduced spleen weight and lymphocyte blood levels after stroke. Splenic irradiation at 3 and 4 hrs after start of ischemia significantly reduced cerebral infarction volumes measured at 48 hrs and 7 days, respectively. The histological analysis on day 7 revealed reduced counts of microglia, infiltrating T cells, and apoptotic neurons in the rats irradiated at 4 hrs. The noninvasive single-dose procedure of splenic irradiation performed within a time interval of up to 4 hours offers neuroprotection against ischemic stroke possibly by abrogating deployment of splenic cells to the brain.
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