Mechanoporation induced by diffuse traumatic brain injury: An irreversible or reversible response to injury?
Mechanoporation induced by diffuse traumatic brain injury: An irreversible or reversible response to injury?
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DOI：
10.1523/jneurosci.5119-05.2006
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发表时间：
2006-03-22
影响因子：
5.3
通讯作者：
Povlishock, JT
中科院分区：
文献类型：
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作者：
Farkas, O;Lifshitz, J;Povlishock, JT
弥漫性创伤性脑损伤（dbi）与神经元质浆破坏相关，可导致坏死或反应性改变，但不会导致细胞死亡。本研究考察了持久的膜扰动是否持续发生，从而导致细胞死亡，或者是否有可能发生短暂的扰动，然后再闭合/恢复。我们还研究了这些事件与calpain介导的谱蛋白水解（CMSP）的关系。为了评估质浆破坏，21只大鼠（n = 21）在dbi前2小时接受脑室内输注正常排除的10 kDa荧光团标记葡聚糖。为观察大鼠损伤后2小时（n = 10）或6小时（n = 11）再给大鼠注射标记右旋糖酐。150 kDa谱蛋白分解产物的免疫组织化学评价了CMSP的伴随作用。用共聚焦显微镜和电镜观察新皮层神经元。dbi后4和8小时，55%的示踪剂灌注神经元含有右旋糖酐，显示出持久的浆质渗漏，许多显示出坏死。在4小时、12.0%和8小时时，15.7%的双示踪剂注入神经元显示CMSP，但这些细胞的变化程度较低。在4小时、39.0%和8小时时，24.4%的示踪剂灌注神经元仅显示损伤前葡聚糖摄取，与膜重封一致，而分别有7.6和11.1%的示踪剂灌注神经元显示CMSP。在4小时，35%和8小时，33%的神经元表现为CMSP，没有右旋糖酐泛洪。在4小时、5.5%和8小时，20.9%的示踪剂灌注神经元仅显示损伤后葡聚糖摄取，与延迟膜摄动一致，分别有55.0%和35.4%的示踪剂灌注神经元显示CMSP。这些研究表明，dbi引起了不断发展的浆质变化，这些变化突出了膜穿孔的机械和潜在的次要事件。
Diffuse traumatic brain injury (DTBI) is associated with neuronal plasmalemmal disruption, leading to either necrosis or reactive change without cell death. This study examined whether enduring membrane perturbation consistently occurs, leading to cell death, or if there is the potential for transient perturbation followed by resealing/recovery. We also examined the relationship of these events to calpain-mediated spectrin proteolysis (CMSP). To assess plasmalemmal disruption, rats ( n = 21) received intracerebroventricular infusion 2 h before DTBI of a normally excluded 10 kDa fluorophore-labeled dextran. To reveal plasmalemmal resealing or enduring disruption, rats were infused with another labeled dextran 2 h ( n = 10) or 6 h ( n = 11) after injury. Immunohistochemistry for the 150 kDa spectrin breakdown product evaluated the concomitant role of CMSP. Neocortical neurons were followed with confocal and electron microscopy. After DTBI at 4 and 8 h, 55% of all tracer-flooded neurons contained both dextrans, demonstrating enduring plasmalemmal leakage, with many demonstrating necrosis. At 4 h, 12.0% and at 8 h, 15.7% of the dual tracer-flooded neurons showed CMSP, yet, these demonstrated less advanced cellular change. At 4 h, 39.0% and at 8 h, 24.4% of all tracer-flooded neurons revealed only preinjury dextran uptake, consistent with membrane resealing, whereas 7.6 and 11.1%, respectively, showed CMSP. At 4 h, 35% and at 8 h, 33% of neurons demonstrated CMSP without dextran flooding. At 4 h, 5.5% and at 8 h, 20.9% of tracer-flooded neurons revealed only postinjury dextran uptake, consistent with delayed membrane perturbation, with 55.0 and 35.4%, respectively, showing CMSP. These studies illustrate that DTBI evokes evolving plasmalemmal changes that highlight mechanical and potential secondary events in membrane poration.