In vivo two-photon microscopy study of short-term effects of microbeam irradiation on normal mouse brain microvasculature.
OBJECTIVE
The purpose of this study was to assess the early effects of microbeam irradiation on the vascular permeability and volume in the parietal cortex of normal nude mice using two-photon microscopy and immunohistochemistry.


METHODS
The upper part of the left hemisphere of 55 mice was irradiated anteroposteriorly using 18 vertically oriented beams (width 25 microm, interdistance 211 microm; peak entrance doses: 312 or 1000 Gy). At different times after microbeam exposure, the microvasculature in the cortex was analyzed using intravital two-photon microscopy after intravascular injection of fluorescein isothiocyanate (FITC)-dextrans and sulforhodamine B (SRB). Changes of the vascular volume were observed at the FITC wavelength over a maximum depth of 650 mum from the dura. The vascular permeability was detected as extravasations of SRB.


RESULTS
For all times (12 h to 1 month) after microbeam irradiation and for both doses, the FITC-dextran remained in the vessels. No significant change in vascular volume was observed between 12 h and 3 months after irradiation. Diffusion of SRB was observed in microbeam irradiated regions from 12 h until 12 days only after a 1000 Gy exposure.


CONCLUSIONS
No radiation damage to the microvasculature was detected in normal brain tissue after a 312 Gy microbeam irradiation. This dose would be more appropriate than 1000 Gy for the treatment of brain tumors using crossfired microbeams.
INSERM, U 594, Functional and Metabolic Neuroimaging, Grenoble, France; Université Joseph Fourier Grenoble, Grenoble, France. rserduc@ujf-grenoble.fr
Raphaël
R
Serduc
Pascale
P
Vérant
Jean-Claude
JC
Vial
Régine
R
Farion
Linda
L
Rocas
Chantal
C
Rémy
Taoufik
T
Fadlallah
Elke
E
Brauer
Alberto
A
Bravin
Jean
J
Laissue
Hans
H
Blattmann
Boudewijn
B
van der Sanden
D000818:Animals; D001522:Behavior, Animal / Q000528:radiation effects; D001810:Blood Volume; D001812:Blood-Brain Barrier / Q000473:pathology / Q000528:radiation effects*; D001921:Brain / Q000098:blood supply* / Q000473:pathology / Q000528:radiation effects; D002199:Capillary Permeability / Q000502:physiology / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D008833:Microcirculation / Q000528:radiation effects; D018613:Microscopy, Confocal / Q000379:methods; D023421:Models, Animal; D011833:Radiation Injuries, Experimental / Q000473:pathology*; D011879:Radiotherapy Dosage; D013997:Time Factors