Increased Expression of Vascular Endothelial Growth Factor-D Following Brain Injury

Abstract

Alterations in the expression of the vascular endothelial growth factors (VEGF) A and B occur during blood–brain barrier (BBB) breakdown and angiogenesis following brain injury. In this study, the temporal and spatial expression of VEGF-D and VEGF receptors-2 and -3 (VEGFR-2 and VEGFR-3, respectively) was determined at the mRNA and protein level in the rat cortical cold-injury model over a period of 0.5 to 6 days post-injury. In order to relate endothelial VEGF-D protein expression with BBB breakdown, dual labeling immunofluorescence was performed using antibodies to VEGF-D and to fibronectin, a marker of BBB breakdown. In control rats, VEGF-D signal was only observed in scattered perivascular macrophages in the cerebral cortex. The upregulation of VEGF-D mRNA expression was observed in the injury site between days 0.5 to 4, coinciding with the period of BBB breakdown and angiogenesis. At the protein level, intracerebral vessels with BBB breakdown to fibronectin in the lesion on days 0.5 to 4 failed to show endothelial VEGF-D. Between days 0.5 to 6, an increased VEGF-D immunoreactivity was noted in the endothelium of pial vessels overlying the lesion site, in neutrophils, macrophages, and free endothelial cells within the lesion. The upregulation of VEGFR-2 and -3 mRNA and protein expression was observed early post-injury on day 0.5. Although there was concurrent expression of VEGF-A, VEGF-B, and VEGF-D post-injury, differences in their spatial expression during BBB breakdown and angiogenesis suggest that they have specific and separate roles in these processes.

Limited Impact of Human Cytomegalovirus Infection in African Infants on Vaccine-Specific Responses Following Diphtheria-Tetanus-Pertussis and Measles Vaccination

“…The lack of impact of HCMV infection on measles-specific innate pro-inflammatory cytokines IL-1β and TNF, the Th1 cytokine IFN-γ, the Th2 cytokine IL-4 and the anti-inflammatory cytokine IL-10 is encouraging. The clinical significance of lower VEGF production is uncertain but it is an important vascular growth factor that has also been linked with trauma and malignancy (39,40). Effects on tetanus toxoid-specific responses similarly showed lower GMCSF and eotaxin in the HCMV+ infants but no effect on innate pro-inflammatory, Th1, Th2 cytokines or IL-10.…”

Traumatic Brain Injury and Blood–Brain Barrier (BBB): Underlying Pathophysiological Mechanisms and the Influence of Cigarette Smoking as a Premorbid Condition

“…Moreover, the upregulation of VEGF, as a major regulator of endothelial cell proliferation, angiogenesis, and vascular permeability as well as the downregulation of claudin-5 expression was correlated to BBB dysfunction [26,33,78,79].…”

Evaluation of the growth factors VEGF-a and VEGF-B in the vitreous and serum of patients with macular and retinal vascular diseases

“…VEGF-B has low angiogenic activity; however, it is a potent anti-apoptotic, rescuing vessels from death. It plays a specific role in angiogenesis during the repair process after brain injury and myocardium revascularization after myocardial infarction (Li et al, 2008;Nag et al, 2002). VEGF-B also plays an important role in the lipid metabolism, and its impairment causes obesity due to absorption and accumulation of fatty acids in the tissues.…”