Zhang Z, Guth L
Department of Neuroscience, University of Virginia School of Medicine, Charlottesville 22908, USA.
Exp Neurol. 1997 Sep;147(1):159-71. doi: 10.1006/exnr.1997.6590.
The presence of adequate blood supply is a critical factor in recovery from traumatic injuries. We have examined whether the revascularization of the injured tissues is as crucial a precondition for wound healing in the spinal cord as in other organs. The development of the initial primary lesion (PL) after spinal crush injury in rats is followed by the formation of a unique tunnel-like dorsal column lesion (DCL) that extends rostrocaudally for many millimeters from the primary injury site. The DCL has been shown to result from Wallerian degeneration of the long spinal tracts in the dorsal column. In this study, we compared the processes of revascularization, wound healing, and nerve regeneration in the PL and the DCL by light microscopy after a crush injury of the cord. The spinal cord of 54 adults rats was crushed at T8 with jewelers forceps. The rats were allowed to survive from 3 h up to 8 weeks after spinal cord injury. The PL appeared immediately after injury and the DCL began to develop 6 h later. Infiltration of neutrophils, which is the first sign of the inflammatory responses to injury, began several hours later in the DCL than in the PL. Secondary vascular injury then occurred which resulted in hemorrhage around the DCL and rapid enlargement of the lesion during the remainder of the first week. Subsequent changes in the PL and DCL were entirely different. The PL underwent progressive enlargement and cavitation such that by 8 weeks, the lesion contained only very few cells, vessels, and axons scattered between huge fluid-filled cavities. The DCL, on the other hand, was maximal in size at 1 week and declined significantly in size and cavitation thereafter. By 8 weeks it was highly vascularized, contained abundant nerve fibers, and lacked any trace of cavitation. These findings amplify the current view that ischemia plays a critical role in spinal cord trauma by showing that revascularization precedes tissue repair and nerve regeneration in the dorsal columns. We conclude (a) that a well-vascularized lesion permits the ingrowth of glial and other cells which give rise to a supportive matrix for the nerve regeneration and (b) that procedures which induce revascularization or angiogenesis will ameliorate the cascade of progressive tissue necrosis.
充足的血液供应是创伤性损伤恢复的关键因素。我们研究了受伤组织的血管再生对于脊髓伤口愈合是否像在其他器官中一样是至关重要的前提条件。大鼠脊髓挤压伤后最初原发性损伤(PL)的发展,随后会形成一种独特的隧道样背柱损伤(DCL),该损伤从原发性损伤部位向头尾方向延伸数毫米。已表明DCL是由背柱中长脊髓束的华勒氏变性导致的。在本研究中,我们通过脊髓挤压伤后光镜检查比较了PL和DCL中的血管再生、伤口愈合和神经再生过程。用珠宝商用镊子在T8水平挤压54只成年大鼠的脊髓。大鼠在脊髓损伤后存活3小时至8周。PL在损伤后立即出现而DCL在6小时后开始形成。中性粒细胞浸润是对损伤炎症反应的第一个迹象,在DCL中比在PL中晚数小时开始。随后发生继发性血管损伤,导致DCL周围出血以及在第一周剩余时间内损伤迅速扩大。PL和DCL随后的变化完全不同。PL逐渐扩大并形成空洞,以至于到8周时,损伤仅包含极少数散在于巨大充满液体的空洞之间的细胞、血管和轴突。另一方面,DCL在1周时大小达到最大,此后大小和空洞程度显著下降。到8周时,它血管高度丰富,含有丰富的神经纤维,并且没有任何空洞的痕迹。这些发现通过表明背柱中血管再生先于组织修复和神经再生,强化了当前关于局部缺血在脊髓创伤中起关键作用的观点。我们得出结论:(a)血管良好的损伤允许神经胶质细胞和其他细胞向内生长,从而为神经再生形成支持性基质;(b)诱导血管再生或血管生成的程序将改善进行性组织坏死的级联反应。