Quantitative Study of Blood.Brain Barrier Permeability Changes after Experimental Whole-Brain Radiation

Abstract

Basic mechanisms underlying the tolerance and reaction of the central nervous system to ionizing radiation are not known precisely. We investigated the possibility of a change in blood-brain barrier (BBB) function as a causative factor for early delayed whole-brain radiation-induced cerebral dysfunction. Rats were exposed to conventional fractionation (200 cGy/d, 5 d/wk; total dose, 4000 cGy). BBB changes were assessed by means of the quantitative 14C-alpha-aminoisobutyric acid technique and electron microscopy. Studies of the passage of horseradish peroxidase across the BBB permitted comparative quantitative isotopical and qualitative morphological data. Experiments were carried out 2 to 3 weeks after the completion of the radiation exposure. The transport of 14C-alpha-aminoisobutyric acid across the BBB increased significantly in cerebral cortex and cerebellar gray matter, averaging 1.3 to 1.5 times over the normal values. Electron microscopy disclosed an intense vesicular response of the cortical microvascular endothelium that occurred without the opening of the tight junctions and resulted in an intense transport of HRP across the intact endothelium. The present data indicate that moderate doses of whole-brain radiation induce well-defined changes in BBB function, which possibly are involved in the pathogenesis of radiation-induced cerebral dysfunction in humans.

Computed Tomography Perfusion Assessment of Radiation Therapy Effects on Spinal Cord Hemodynamics

“…Two models of BBB opening secondary to radiation are postulated: (1) endothelial shrinkage and/or capillary dilatation with opening of the interendothelial tight junctions; and (2) Increased vesicular activity with an increased transfer of material between blood and brain either by the transport of microvesicles across the endothelium or by the coalescence of vesicles to form continuous intracellular channels through the endothelium (19). D'Avella et al exposed 10 rats to whole-brain radiation (total dose 40 Gy) and, using radiotracer techniques, found a generalized increase in intracranial capillary permeability compared with controls at 2 to 3 weeks after treatment completion (20). Electron microscopy evaluations of rat brain specimens 2 weeks after whole-brain irradiation demonstrated increased vesicular transport across the endothelium, with intact vascular tight junctions; 90 days after whole-brain irradiation, collapse of the cortical microvasculature and perivascular edema were observed, with significantly decreased vesicular activity perhaps indicative of initial functional recovery of the BBB (19,20).…”

“…D'Avella et al exposed 10 rats to whole-brain radiation (total dose 40 Gy) and, using radiotracer techniques, found a generalized increase in intracranial capillary permeability compared with controls at 2 to 3 weeks after treatment completion (20). Electron microscopy evaluations of rat brain specimens 2 weeks after whole-brain irradiation demonstrated increased vesicular transport across the endothelium, with intact vascular tight junctions; 90 days after whole-brain irradiation, collapse of the cortical microvasculature and perivascular edema were observed, with significantly decreased vesicular activity perhaps indicative of initial functional recovery of the BBB (19,20). Two main hypotheses have been proposed as to the likely mechanisms leading to the development of radiation myelopathy; these are known as the glial and the vascular hypotheses (27).…”

“…Based on prior animal studies on the effects of central nervous system irradiation (18)(19)(20)(21), we hypothesized that RT could cause an acute perturbation of SC perfusion during radiation treatment.…”

Limited Contribution of Circulating Cells to the Development and Maintenance of Nonhematopoietic Bovine Tissues

“…For reprints contact: Reprints@AlphaMedPress. com Niku, Ilmonen, Pessa-Morikawa et al 13 increasing collagen synthesis and angiogenesis in a few days [20][21][22]. The origin of the granulation tissue producing cells is unclear, with several contradictory studies supporting either a local or systemic source [23,24].…”

“…However, the physiological significance of the findings is uncertain. The cell culture techniques and transplantation methods applied are likely to induce changes both in the cells [11] and recipient tissues [12,13]. Also, heterogeneity of the transplanted cell populations [14], potential cell fusion events [15,16], and problems in reproducing some of the results [17,18] complicate interpretation of transdifferentiation experiments.…”