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Pathogenesis

The effect of X-ray irradiation to the adult CNS is dose-dependent (Zeman 1963, 1964):

— 100 Gy: whole body irradiation causes immediate death.

— 70 Gy: local irradiation causes acute necrosis of white and gray matter.

— 50-70 Gy: local irradiation causes partial tissue necrosis.

— 20-25 Gy: local irradiation causes delayed white matter necrosis because X-rays induce the functional impairment of oligodendrocytes (Blake-more 1978) and endothelial cells (Blakemore and Palmer 1982).

According to Schmitt (1983) local application of ionizing radiation to the CNS can have the following effects:

— Inactivation of enzymes, generation of free radicals, and/or loss of binding sites on molecules and atoms.

— Oxygen free radical damage to DNA (Ravanat et al. 2001) with loss of the ability of DNA to replicate; it can damage chromosomes and cause mutations and abnormal cell growth.

— Reduction of brain metabolism, especially cerebral consumption of glucose (d'Avella et al. 1994).

— Death of cells (Chan et al. 1999) and organelles ensuing from destruction of the organic molecular structure.

— Changes in the cerebral arterial wall due to the sensitivity of endothelial cells and smooth muscle cells to irradiation (O'Connor and Mayberg 2000).

— The developing brain is highly sensitive to X-ray and CNS malformation may be the consequence of X-ray exposure during pregnancy (Sundaresan et al. 1978).

Cell division is blocked by X-rays by three different pathways:

1. Mitosis is irreversibly interrupted and the cell will die by apoptosis when exposed during the G1- and S-phases (Ferrer et al. 1993).

2. X-irradiation induces the production of free radicals and inhibits DNA repair enzymes with the result of cell death by necrotic mechanisms.

3. There are indications of an increase in apoptosis as well as active caspase-3 expression following exposure to radiation (Marshman et al. 2001). These investigations are based on irradiated intestine, but may reflect basic principles of radiation injury.

Fig. 12.3a-d. Radiation injury. a-c Vasculopathy marked by treme gliosis; (a, b trichrome stain; c van Gieson stain; d Holzer hyalinization of the vascular wall without fibrinoid necrosis; d ex- stain; magnification a, c, d X300; b Xl,000)

Radiation energy acts through radiolysis of water molecules to trigger the release of OH and H radicals, which react with amino acids and SH groups on the membranes of cells and organelles. With regard to complex molecules, radiation can alter the activity of enzymes, giving rise to an accumulation of enzyme-dependent substances. The decisive pathogenetic factor is damage to the capacity of cells to reproduce, resulting in acute radiation necrosis and mutations. The most vulnerable cells are those capable of mitosis within the CNS, i.e., glial cells as well as endothelial and muscle cells of vessel walls (Hopewell 1979; Schmitt 1983).

The histopathological findings in vessels following irradiation include thickening of vessel walls, thrombosis, luminal occlusion, and occasional tel-angiectasis (O'Connor and Mayberg 2000). In the early stages, the combined effect of irradiation on vascular walls and parenchyma causes damage to the oligodendroglia and the remaining parenchyma; in later stages, injury of vascular walls predominates (O'Connor and Mayberg 2000). The injury is thought to be mediated by cytokines and growth factors (Kureshi et al. 1994) released from hematopoietic and local cells.

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