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KMID : 0350519930460010363
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Journal of Catholic Medical College
1993 Volume.46 No. 1 p.363 ~ p.377
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The Effect of Prednisolone following Whole Brain Irradiation on Blood-Barrier of the Mouse -In the View of Acute Change-
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Abstract
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Knowledge of the blood-brain barrier(BBB) has increased immensely during last 3 decades, mostly because of the devlopment of methods used for the study of it´s structure and function. A special subject within the topic about pathophysiology of BBB is
the impatirment of BBB by ionizing radiation. The alteration of the integrity of BBB is manifestation of radiation injury to the morphologic structures forming the BBB that is endothehal cells of brain capillaries and neghboring astrocytfes. The radiation induced BBB breaddown is of interest in the view of pathophysiological mechanism leading to the development of acute brain edema in not only conventionally fractionated irradiation but also single dose irradiation such as stereotactic radiosurgery or interstitial brachytherapy on the brain. Glucocortioids are widely used concurrently with radiotherapy for their putative salutary effect on intracranial hypertension and brain edema. But the mechanism of sction of glucocortioid on the afficted brain remains for the most part an enigma.
In the present study, e try to determine peak time of radiation damage of BBB of mice that correlated with appropriate time for effective administration of chemotheraperutic agents in clinical situatin. We also observed whether prednisolone can reduce rediation change in BBB and determine the time of maximal stabilization. Mice was sacrificed on the lst, 3rd, 5th 7th and 9th day after whole brain irradiation(single dose 20 Gy) with or without administration of prednisolone and inraperitoneal injection of tryphan blue for gross observation. The radiation change was evaluated microscopically by scoring of histologic damage.
@ES The results were as follows :
@EN 1. Significant difference in percentage of vital staining was noted between radiation group(21/2584%) and radiation-prednisolone group(14/25, 56%)(P=0.05).
2. Predilection sites of vital staining were brain stem(68%), hypothalamus(40%), olfactary bulb(36%), cerebral cortex(28%) and cerebellum(18%) in orde of frequency
3. Radiation-prednisolone group had significantly lower histologic damage scores for intracellular $ interstitial edema(P=0.0008), change of astrocyte(P=0.016), and extravastion of RBC(P=0.0385) compaired with radiation grup, respectively. The most prominent differences in between radiation group and radiation-prednisolone group was noted on 3rd day. The highest histologic damage score was noted on 7th day.
4. The mean scores for three histologic parameters according to elapsed days after radiation had significant differences(P=0.0003).
5. The mean scores for three histologic parameters according to treatment modality(radiation alone Vs radiation-prednisolone group) had signifiant differences(P=0.0001).
6. Elapsed days after radiation and treatment modalities were statistically independent variable(P=0.024).
7. The histologic damage scores on 3rd day(P=0.001) and 5th day(P=0.0264) had significant differences in between radiation group and radiation-prednisolone group.
8. The area of severe histologic damage correspond with region of siginificant tryphan blue coloration .
These results suggest that the peak time of acute radiation damage related to appropriate time for chemotherapy is 7th days after whole brain irradiation, and that the prednisolone has significant salutary effect on the radiation-induced change of the BBB at 3rd and 5th days after 20 Gy whole brain irradiation. But the differences according to total radiation dose $ fractionated dose and species were considered for clinical application of these results. From now on, Quantitative mesurement of change and electron microscopic examination for clarification of mechanism are recommended in the further experiment with variable dose-schedules.
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