Alteration Of Myelin In Rat Brain After Irradiation

Purpose The aim of this study was to investigate demyelination histomorpho -logically and to assess alterations in myelin and its gene expression after irradiation in rat and to probe the pathogenesis of irradiation-induced demyelination. Methods Adult rats were administrated single doses of 2, 10 and 30Gy to the whole brain and were then sacrificed at intervals of 1 week, 1,3 and 6 months after exposure. HE staining was used to observe the histomorphological changes. Kluver Barrera staining was used to assess demyelination. Demyelination was quantified using an ELISA-based assay for MBP. Changes in myelin gene expression were measured using RT-PCR for MBP.Results 1. In control group ,astrocytes, oligodendrocytes and microglials distributed in fimbria of rats. Oligodendrocytes were rarely seen at 2Gy after lweek,l month and 3 months. The number of oligodendrocyte somewhat increased at 2Gy after 6m, but it remained lower than that of control group. While oligodendrocytes were rarely and seen at lweek,l month,3 months and 6months after irradiation of 10Gy and 30Gy. The number of astrocyte significantly decreased at 2Gy after lweek and at 10Gy and 30Gy after lweek,l month and 3 months, but it increased and exceeded that of controls at 2Gy after lmonth,3months and 6months and 10Gy and 30Gy after 6m. Dying gliocytes were observed in fimbria of rat at 2Gy after lweek and at lOGy and 30Gy after lweek,l month and 3 months. Edmea was observed in matrix of fimbria in all irradiated rats, while at 30Gy after 6 months. Demyelination was observed in corpus callosum of rats. 2 There was no significant change in concentration of MBP in control group. The concentration of MBP siginificently decreased at 10Gy and 30Gy after 3months and at 2Gy, lOGy and 30Gy after 6months compared to controls. The concentration of MBP was correlated negatively to the irradiation does in 3 months and 6 months after exposure. The concentration of MBP was correlated negatively to post-irradiation time. 3. There was no significant alteration in the level of MBP gene expression in controls. There was no notable deletion in the level of MBP gene expression in irradiated rats at lweek after exposure. There weresignificant depressions at lOGy and 30Gy after 1 month and 2Gy, lOGy and 30Gy after 3months, while at 6months after exposure MBP gene level of 2Gy, lOGy and 30Gy group recovery to that of control.Conclusion 1. There was significant hitomorphological abnormality during acute and sub-acute stage after irradiation. The major lesion are the death of neurons and gliocytes, edmea in matrix and increase in the number of astrocytes. The lesion in large does is more severity and exists longer than that in low does. 2. Irradiation-induced demyelination may be time and does-dependent, and time and does may be one of the most major factors effecting demyelination. 3. The expression level of MBP gene correlates with irradiation does and post-irradiation time. The suppression in MBP gene occurs earlier and exists longer in large does group than in low ones. There is a tendency that MBP gene expression level decreases and increases latterly. 4. The alteration in MBP gene expression occurs earlier than that in MBP protein expression. The inhibition in MBP gene expression may be one of the most major factors inducing reduction in MBP protein expression. 5. The occurrence of irradiation-induced demyelination may not correlate with the irradiation does after exposure to 2Gy~30Gy X-ray. The extent of irradiation-induced demyelination may correlate with the irradiation does. 6. ELISA assay for MBP is more sensitive than Kluver Barrera staining to measure demyelination.