Low-dose photodynamic therapy increases endothelial cell proliferation and VEGF expression in nude mice brain.
We tested whether low-dose photodynamic therapy (PDT) induces an angiogenic response in the normal brain of nude mice (n=20). Normal brains of nude mice were subjected to PDT at low doses (Photofrin: 2 mg/kg; optical: 2 J/cm(2) and 4 J/cm(2)). BrdU (50 mg/kg) was injected (intraperitoneally, i.p.) daily from PDT treatment to sacrifice (1 and 2 weeks after PDT). Laser scanning confocal microscopy, immunohistochemistry, and immunofluorescence staining were performed to assay angiogenic response. Morphological results show no significant tissue damage induced by PDT and two- and three-dimensional image analyses revealed no significant difference in vascular structure between the areas of exposure to PDT and contralateral areas in all mice. However, the number of BrdU immunoreactive cells were significantly increased in the areas of PDT treatment compared with contralateral hemisphere in both groups, and the number of BrdU-positive cells increased in a PDT-dose-dependent manner. Furthermore, immunohistochemical data indicate that PDT at these low doses significantly induces the expression of the vascular endothelial growth factor (VEGF) in PDT-treated regions in the 1-week group, but not in the 2-week group. These data indicate that low-dose PDT results in increased VEGF expression and endothelial cell proliferation in normal brains.
Zhang
Xuepeng
X
Neurology Department, Henry Ford Health Sciences Center, Henry Ford Hospital, 2799 West Grand Blvd., Detroit, MI 48202, USA.
Jiang
Feng
F
Zhang
Zheng Gang
ZG
Kalkanis
Steven N
SN
Hong
Xin
X
deCarvalho
Ana C
AC
Chen
Jieli
J
Yang
Hongyan
H
Robin
Adam M
AM
Chopp
Michael
M
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001973:Bromodeoxyuridine / Q000494:pharmacology; D049109:Cell Proliferation; D017323:Dihematoporphyrin Ether / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D042783:Endothelial Cells / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D018919:Neovascularization, Physiologic; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D017319:Photosensitizing Agents; D011838:Radiation-Sensitizing Agents; D042461:Vascular Endothelial Growth Factor A; D017323:Dihematoporphyrin Ether; D001973:Bromodeoxyuridine