title: Serial in vivo observations of cerebral vasculature after treatment with a large single fraction of radiation.
abstract: To test whether single high doses of radiation, similar to those used with radiosurgery, given to normal cerebral vasculature can cause changes in leukocyte-vessel wall interactions and tissue perfusion, a rat pial window model was used to view the cerebral vasculature, facilitating repeated in vivo observations of microcirculatory function. An attachment for a 4 MV linear accelerator was designed to deliver a well-collimated 2.2-mm beam of radiation to a selected region of rat brain. Sequential measurements of leukocyte-endothelial cell interactions, relative change in blood flow with laser Doppler flowmetry and vessel length density were performed prior to and at 24 h and 3 weeks after treatment with 15, 22.5 or 30 Gy, given in a single fraction. Significant increases in leukocyte-endothelial cell interactions were seen 24 h and 3 weeks after irradiation that were dependent on dose, particularly in arteries. Changes were apparent in both arteries and veins at 24 h, but by 3 weeks the effects in arteries predominated. Decreases in vessel length density and blood flow were observed and became greater with time after treatment. A variety of morphological changes were observed in irradiated arteries, including formation of aneurysmal structures, endothelial denudation and thrombus formation. These results suggest that: (1) An increase in leukocyte-vessel wall interactions occurs after irradiation; (2) cerebral arterioles are more sensitive than veins to radiation administered in this fashion; and (3) the increase in leukocyte-vessel wall interactions likely contributes to reduction of or loss of arteriolar flow, with resultant loss of flow to dependent microvascular vessels.
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Acker
authors.forename: L B
authors.initials: LB
authors.lastname: Marks
authors.forename: D P
authors.initials: DP
authors.lastname: Spencer
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.forename: M A
authors.initials: MA
authors.lastname: Avery
authors.forename: R K
authors.initials: RK
authors.lastname: Dodge
authors.forename: G L
authors.initials: GL
authors.lastname: Rosner
authors.forename: M W
authors.initials: MW
authors.lastname: Dewhirst
mesh_terms: D000818:Animals; D001167:Arteritis / Q000209:etiology; D001921:Brain / Q000098:blood supply / Q000528:radiation effects*; D002448:Cell Adhesion; D002560:Cerebrovascular Circulation / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004730:Endothelium, Vascular / Q000166:cytology; D007962:Leukocytes / Q000166:cytology; D011833:Radiation Injuries, Experimental / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors