Experimental spinal cord injury: Wallerian degeneration in the dorsal column is followed by revascularization, glial proliferation, and nerve regeneration.
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.
Zhang
Z
Z
Department of Neuroscience, University of Virginia School of Medicine, Charlottesville 22908, USA.
Guth
L
L
D000818:Animals; D002455:Cell Division; D005260:Female; D018919:Neovascularization, Physiologic; D009416:Nerve Regeneration; D009457:Neuroglia / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000098:blood supply* / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors; D014855:Wallerian Degeneration