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25 May 2018 Postirradiation Necrosis after Slow Microvascular Breakdown in the Adult Rat Spinal Cord is Delayed by Minocycline Treatment
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Abstract

To better understand the spatiotemporal course of radiation-induced central nervous system (CNS) vascular necrosis and assess the therapeutic potential of approaches for protecting against radiation-induced necrosis, adult female Sprague Dawley rats received 40 Gy surface dose centered on the T9 thoracic spinal cord segment. Locomotor function, blood-spinal cord barrier (BSCB) integrity and histology were evaluated throughout the study. No functional symptoms were observed for several months postirradiation. However, a sudden onset of paralysis was observed at approximately 5.5 months postirradiation. The progression rapidly led to total paralysis and death within less than 48 h of symptom onset. Open-field locomotor scores and rotarod motor coordination testing showed no evidence of neurological impairment prior to the onset of overt paralysis. Histological examination revealed minimal changes to the vasculature prior to symptom onset. However, Evans blue dye (EvB) extravasation revealed a progressive deterioration of BSCB integrity, beginning at one week postirradiation, affecting regions well outside of the irradiated area. Minocycline treatment significantly delayed the onset of paralysis. The results of this study indicate that extensive asymptomatic disruption of the blood-CNS barrier may precede onset of vascular breakdown by several months and suggests that minocycline treatment has a therapeutic effect by delaying radiation-induced necrosis after CNS irradiation.

©2018 by Radiation Research Society.
Karen L. Lankford, Edgardo J. Arroyo, and Jeffery D. Kocsis "Postirradiation Necrosis after Slow Microvascular Breakdown in the Adult Rat Spinal Cord is Delayed by Minocycline Treatment," Radiation Research 190(2), 151-163, (25 May 2018). https://doi.org/10.1667/RR15039.1
Received: 18 January 2018; Accepted: 4 April 2018; Published: 25 May 2018
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