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J. Swartz, B. J. Slater, A. Puche, S. L. Bernstein; Optic Nerve Stroke Induces Rapid Changes in Vascular Structure. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2457.
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Optic nerve stroke is the most common cause of sudden optic nerve-related vision loss, but we do not understand many of the vascular changes occurring after injury. Furthermore, it is unclear how focal insults affect far distal vasculature and how these alterations progress over time. We wanted to better understand the speed and nature of vascular changes following optic nerve infarct.
We induced a mouse optic nerve stroke (rAION) using published methods (Goldenberg-Cohen et al, IOVS, 2005). At one day post-stroke eight adult male mice were intra-cardially perfused with a gelatin solution containing fluorescein-bovine serum albumin (66 kDa) and Rhodamine-Dextran (3 kDa). Post-fixation, fifty micron-thick frozen sections were serially imaged as optical stacks on an Olympus Fluoview 500 confocal microscope. Optic nerve vascular mapping was performed using Neurolucida software (MicroBrightField, Williston, VT) and vessels were not only visualized, but reconstructed in three dimensions to quantitatively determine the extent of the damage to the lesion site.
Reconstruction of the optic nerve vasculature revealed both the areas of stroke and an area of surrounding edema. There was a massive loss of vascular supply one day after stroke extending at least 500 micrometers distally from the site of damage. Significant changes in both total vessel length and density were seen. However, vascular supply was apparently intact greater than 2000 micrometers distal to the primary lesion. No obvious changes were detected in retinal vasculature.
Analysis of optic nerve vasculature, using multiple molecular weight fluorescent markers, combined with confocal vascular mapping and reconstruction is a powerful tool for studying the extent and nature of stroke-associated damage. We find that the insult caused by optic nerve stroke does not simply localize to the injury site. Rather, there is extension to the distal vasculature relatively quickly, suggesting that neurovascular coupling is affected following focal ON stroke. Better understanding of the association of primary vascular damage and later vessel-related events may help elucidate possible treatment options following strokes.
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