Acceleration of normal-tissue damage expression by early stimulation of cell proliferation in rat spinal cord.
OBJECTIVE
To examine experimental strategies for prevention of radiation-induced late spinal cord damage.


METHODS
The effects of treatment with high, proliferation-stimulating doses of platelet-derived growth factor (PDGF) administered at various times after radiotherapy of rat spinal cord, and aiming at increased tissue regeneration, were studied in an established model. Animals were followed and monitored for expression of radiation myelopathy (RM), which was confirmed by histopathologic diagnosis.


RESULTS
High doses of PDGF given 8 weeks after radiotherapy significantly accelerated the development of RM compared to control animals (Figure 1). Such effects were observed also for concomitant treatment, but not for PDGF administration after 12 or 15 weeks (Figure 2). On the microscopic level, the spinal cord showed more pronounced vascular damage with vessel necroses and hemorrhages (Figure 3).


CONCLUSIONS
These data suggest that the vascular system plays an important role during development of RM and that early stimulation of cell proliferation negatively influences the time course of spinal cord damage. Further experiments should address different concepts of tissue regeneration or damage prevention.
Nieder
Carsten
C
Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Strasse 22, 81675 Munich, Germany. cnied@hotmail.com
Andratschke
Nicolaus
N
Price
Roger E
RE
Kian-Ang
Kie
K
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D016015:Logistic Models; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000517:prevention & control*; D011836:Radiation Tolerance; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D011878:Radiotherapy / Q000009:adverse effects*; D051381:Rats; D011916:Rats, Inbred F344; D012038:Regeneration; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000502:physiology / Q000528:radiation effects*; D013118:Spinal Cord Diseases / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D016019:Survival Analysis; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000494:pharmacology
D010982:Platelet-Derived Growth Factor; D011837:Radiation-Protective Agents; D042461:Vascular Endothelial Growth Factor A