Early blood-brain barrier disruption after high-dose single-fraction irradiation in rats

Abstract

We studied the effect of high-dose single-fraction irradiation on the permeability of the blood-brain barrier (BBB) in rat brains. Immunohistochemistry with an antibody to serum albumin was used as a sensitive method for detecting the extravasation of endogenous serum components. Extravasation of albumin was detected as early as 1 day after irradiation with 20 or 40 Gy. Immunoreactivity reached its maximum after 3 days, gradually decreased during the following few weeks and had disappeared by day 30. Extravasation was much greater after irradiation with 80 Gy and continued to increase during the whole period of the experiment (6 days). Disruption of BBB this early after irradiation has not been previously documented. The time course of observed serum albumin extravasation, however, agrees well with the previous ultrastructural evidence for increased BBB permeability after irradiation with 27 Gy in monkey brains. This transient impairment of BBB may contribute to the reversible neurological symptoms after radiosurgery. It may also allow drugs that normally not pass the BBB to do so and thus disperse in the brain when administered at this time.

Fractionated Radiation-Induced Acute Encephalopathy in a Young Rat Model: Cognitive Dysfunction and Histologic Findings

“…Vasogenic edema following disruption of the BBB 27 could be an early and readily recognizable pathophysiologic event occurring after irradiation. Nakata et al 28 found that the destruction of the BBB was detectable as early as 1 day after irradiation with 20 or 40 Gy, reached its maximum after 3 days, and gradually decreased during the following few weeks. Yet to the best of our knowledge, no study of the destruction of the BBB and brain edema has been performed in the fractionated-radiation model.…”

An Experimental Study of Acute Radiation-Induced Cognitive Dysfunction in a Young Rat Model

“…Several studies have reported the occurrence of a transient increase of BBB permeability after radiation exposure, though the duration seemed to vary among the reports, and it was suggested to strongly depend on the size and the physicochemical properties of the probes used for the assay. 27 Nakata et al 28 studied the effect of single irradiation on the permeability of the BBB in rat brains and found that the destruction of the BBB was detected as early as 1 day after irradiation with 20 or 40 Gy, reached its maximum after 3 days, and gradually decreased during the following few weeks. The degree of this destruction could become much greater when the irradiation dose increased to 80 Gy and the BBB disruption remained during the whole course of the experiment.…”

Prediction of volumetric change in the “triple ring” caused by glioma I-125 brachytherapy

“…The frequency, 7 intracranial location, 8 mechanism, 9,10 and time evolution of the occurrence of edema after cerebral irradiation 11,12 have been discussed by numerous authors. Helenowski et al 7 investigated 600 patients after linear accelerator irradiation (eight and nine isocenters were used; 65% of the patients had .13.5 cm 3 tumor volume); edema, which could be balanced by steroids, was observed in 30% of the patients.…”