Anik Ihsan, Kokturk Sibel, Genc Hamza, Cabuk Burak, Koc Kenan, Yavuz Sadan, Ceylan Sureyya, Ceylan Savas, Kamaci Levent, Anik Yonca
Department of Neurosurgery, School of Medicine, University of Kocaeli, Turkey.
J Spinal Cord Med. 2011;34(3):257-64. doi: 10.1179/107902611X12972448729648.
Thoracic and thoracoabdominal aortic intervention carries a significant risk of spinal cord ischemia. The pathophysiologic mechanisms that cause hypoxic/ischemic injury to the spinal cord have not been totally explained. In normal spinal cord, neurons and glial cells do not express type IV collagen. Type IV collagen produced by reactive astrocytes is reported to participate in glial scar formation. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors that regulate the activity of the matrix metalloproteinases (MMPs). TIMP-2 binds strongly with MMP-2, facilitating activation by membrane-type MMP. Imbalance between TIMPs and MMPs can lead to excessive degradation of matrix components. Type IV collagen involved in the blood-brain barrier disruption and glial scar formation, TIMP-2 influences MMP-2 that controls degradation of collagen I and IV.
To examine the immunohistochemical analysis of TIMP-2 and collagen types I-IV in experimental spinal cord ischemia-reperfusion in rats.
Thirty-two male Wistar rats weighing 250-300 g were divided into four groups: group S: sham group (n = 8); group 0P: 30-minute occlusion without perfusion (n = 8); group 3P: 30-minute occlusion and 3-hour perfusion (n = 8); and group 24P: 30-minute occlusion and 24-hour perfusion (n = 8). Infrarenal aorta was cross-clamped at two sites by using two aneurysm clips for 30 minutes. Reperfusion was provided after removal of the clips. Lumbar spinal cord segments were removed for immunohistochemical analysis.
TIMP-2 and collagen staining in 3-hour perfused (3P) group were nearly the same with sham group (S). TIMP-2 and collagen staining increased in the 24-hour perfused group.
Alterations in collagen levels may relate to the biphasic breakdown of the blood-brain barrier and collagen staining in new cell types with relation to glial scar formation. Our results demonstrate that 3-hour perfusion after occlusion in hypoxic/ischemic spinal cord injury seems to be the critical reversible period.
胸主动脉及胸腹主动脉介入手术存在脊髓缺血的重大风险。导致脊髓缺氧/缺血性损伤的病理生理机制尚未完全阐明。在正常脊髓中，神经元和神经胶质细胞不表达IV型胶原蛋白。据报道，反应性星形胶质细胞产生的IV型胶原蛋白参与胶质瘢痕形成。金属蛋白酶组织抑制剂（TIMPs）是调节基质金属蛋白酶（MMPs）活性的内源性抑制剂。TIMP-2与MMP-2紧密结合，促进膜型MMP对其激活。TIMPs与MMPs之间的失衡可导致基质成分过度降解。IV型胶原蛋白参与血脑屏障破坏和胶质瘢痕形成，TIMP-2影响控制I型和IV型胶原蛋白降解的MMP-2。
检测大鼠实验性脊髓缺血再灌注中TIMP-2及I-IV型胶原蛋白的免疫组化分析。
将32只体重250 - 300 g的雄性Wistar大鼠分为四组：S组：假手术组（n = 8）；0P组：阻断30分钟但无灌注组（n = 8）；3P组：阻断30分钟并灌注3小时组（n = 8）；24P组：阻断30分钟并灌注24小时组（n = 8）。使用两个动脉瘤夹在两个部位夹闭肾下腹主动脉30分钟。夹闭去除后进行再灌注。取出腰段脊髓节段进行免疫组化分析。
3小时灌注（3P）组的TIMP-2和胶原蛋白染色与假手术组（S）几乎相同。24小时灌注组的TIMP-2和胶原蛋白染色增加。
胶原蛋白水平的改变可能与血脑屏障的双相破坏以及与胶质瘢痕形成相关的新细胞类型中的胶原蛋白染色有关。我们的结果表明，缺氧/缺血性脊髓损伤阻断后3小时灌注似乎是关键的可逆期。
