Delayed central nervous system irradiation effects in rats--part 2: aggravation of experimental autoimmune encephalomyelitis.

Background: Central nervous system (CNS) irradiation has detrimental effects which become evident within hours to few days and after a long latency of months and years. However, the delayed effect of irradiation on neuroimmune diseases has not been thoroughly examined.

Objectives: We evaluated the delayed effects of irradiation on the course of experimental autoimmune encephalomyelitis (EAE), which is used as a model for neuroimmune inflammation and multiple sclerosis.

Methods: Adult male rats were exposed to a dose of 15 Gy given to the thoracolumbar spinal cord. Six months later, EAE was induced by inoculation of rat spinal cord homogenate in complete Freund's adjuvant (CFA). The disease was evaluated by clinical, histopathological and immunological parameters.

Results: Irradiated rats developed clinical signs of EAE earlier than the control group and their disease was much more severe. Unlike the control group, all rats in the EAE-irradiated group died within 5 days after the onset of clinical signs. Sections taken from irradiated rats showed diffuse and large hemorrhagic infiltrates of lymphocytes and granulocytes. In contrast, control rats displayed fewer infiltrates, which were less prominent and not hemorrhagic.

Conclusions: CNS irradiation has a delayed effect that caused a marked aggravation of the clinical and pathological signs of EAE. The severity of the disease may be a consequence of the effect of irradiation on the CNS vascular bed and impaired blood-brain barrier.