Due to the severe and untreatable consequences of radiation myelopathy, many tumors in the paraspinal region receive a less than optimal radiation dose. Even a modest reduction in the risk of radiation injury from a given therapeutic dose would allow for the use of an increased dose which could enhance the probability of a local cure. The ability to accurately assess oxygen concentration in the radiated spinal cord is critical to studying the underlying mechanisms of radiation myelopathy, and in helping to determine more effective ways to use and deliver radiation to cancers in the paraspinal region. Our results show that spinal cord tissue pO2 in the irradiated rats increased significantly at intermediate (maximum level of 18 q 3 mm Hg at 55 days post irradiation) and long time periods after the radiation (average level 15 q 3 mm Hg between 90 and 180 days post irradiation), compared with the non-irradiated control group (average level of 9 q 2 mm Hg throughout the experiment). The finding that the pO2 was elevated in the irradiated spinal cord was unexpected and suggests that the prevailing expectations on the pathophysiology of radiation-induced damage to the spinal cord should be reconsidered. It seems possible that the pathogenesis is related to oxidative damage associated with the increased pO2. Although the mechanisms for the increase in pO2 in this study are not currently known, decreased oxygen consumption and/or radiation induced loss of vascular tone and microvascular remodeling and dilatation in the irradiated region are plausible factors. These results also indicate that EPR oximetry is a useful and noninvasive method for repeatedly assessing the pO2 of CNS tissue non-invasively over an extended period of time.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR011602-05
Application #
6353186
Study Section
Project Start
2000-09-01
Project End
2002-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
5
Fiscal Year
2000
Total Cost
$6,078
Indirect Cost
Name
Dartmouth College
Department
Type
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
Sinha, Birandra K; Leinisch, Fabian; Bhattacharjee, Suchandra et al. (2014) DNA cleavage and detection of DNA radicals formed from hydralazine and copper (II) by ESR and immuno-spin trapping. Chem Res Toxicol 27:674-82
Dunn, Jeff F; Khan, Mohammad N; Hou, Huagang G et al. (2011) Cerebral oxygenation in awake rats during acclimation and deacclimation to hypoxia: an in vivo electron paramagnetic resonance study. High Alt Med Biol 12:71-7
Shen, Jiangang; Khan, Nadeem; Lewis, Lionel D et al. (2003) Oxygen consumption rates and oxygen concentration in molt-4 cells and their mtDNA depleted (rho0) mutants. Biophys J 84:1291-8
Khan, Nadeem; Wilmot, Carmen M; Rosen, Gerald M et al. (2003) Spin traps: in vitro toxicity and stability of radical adducts. Free Radic Biol Med 34:1473-81
Pogue, Brian W; O'Hara, Julia A; Demidenko, Eugene et al. (2003) Photodynamic therapy with verteporfin in the radiation-induced fibrosarcoma-1 tumor causes enhanced radiation sensitivity. Cancer Res 63:1025-33
Hou, Huagang; Grinberg, Oleg Y; Taie, Satoshi et al. (2003) Electron paramagnetic resonance assessment of brain tissue oxygen tension in anesthetized rats. Anesth Analg 96:1467-72, table of contents
Chen, Bin; Pogue, Brian W; Goodwin, Isak A et al. (2003) Blood flow dynamics after photodynamic therapy with verteporfin in the RIF-1 tumor. Radiat Res 160:452-9
Dunn, Jeff F; Swartz, Harold M (2003) In vivo electron paramagnetic resonance oximetry with particulate materials. Methods 30:159-66
Khan, Nadeem; Shen, Jiangang; Chang, Ta Yuan et al. (2003) Plasma membrane cholesterol: a possible barrier to intracellular oxygen in normal and mutant CHO cells defective in cholesterol metabolism. Biochemistry 42:23-9
Swartz, Harold M (2002) Measuring real levels of oxygen in vivo: opportunities and challenges. Biochem Soc Trans 30:248-52

Showing the most recent 10 out of 44 publications