Placental growth factor deficiency is associated with impaired cerebral vascular development in mice.

STUDY HYPOTHESIS: Placental growth factor (PGF) is expressed in the developing mouse brain and contributes to vascularization and vessel patterning. STUDY FINDING: PGF is dynamically expressed in fetal mouse brain, particularly forebrain, and is essential for normal cerebrovascular development. WHAT IS KNOWN ALREADY: PGF rises in maternal plasma over normal human and mouse pregnancy but is low in many women with the acute onset hypertensive syndrome, pre-eclampsia (PE). Little is known about the expression of PGF in the fetus during PE. Pgf  (-/-) mice appear normal but recently cerebral vascular defects were documented in adult Pgf  (-/-) mice. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Here, temporal-spatial expression of PGF is mapped in normal fetal mouse brains and cerebral vasculature development is compared between normal and congenic Pgf  (-/-) fetuses to assess the actions of PGF during cerebrovascular development. Pgf/PGF, Vegfa/VEGF, Vegf receptor (Vegfr)1 and Vegfr2 expression were examined in the brains of embryonic day (E)12.5, 14.5, 16.5 and 18.5 C57BL/6 (B6) mice using quantitative PCR and immunohistochemistry. The cerebral vasculature was compared between Pgf  (-/-) and B6 embryonic and adult brains using whole mount techniques. Vulnerability to cerebral ischemia was investigated using a left common carotid ligation assay. MAIN RESULTS AND THE ROLE OF CHANCE: Pgf/PGF and Vegfr1 are highly expressed in E12.5-14.5 forebrain relative to VEGF and Vegfr2. Vegfa/VEGF is relatively more abundant in hindbrain (HB). PGF and VEGF expression were similar in midbrain. Delayed HB vascularization was seen at E10.5 and 11.5 in Pgf  (-/-) brains. At E14.5, Pgf  (-/-) circle of Willis showed unilateral hypoplasia and fewer collateral vessels, defects that persisted post-natally. Functionally, adult Pgf  (-/-) mice experienced cerebral ischemia after left common carotid arterial occlusion while B6 mice did not. LIMITATIONS, REASONS FOR CAUTION: Since Pgf  (-/-) mice were used, consequences of complete absence of maternal and fetal PGF were defined. Therefore, the effects of maternal versus fetal PGF deficiency on cerebrovascular development cannot be separated. However, as PGF was strongly expressed in the developing brain at all timepoints, we suggest that local PGF has a more important role than distant maternal or placental sources. Full PGF loss is not expected in PE pregnancies, predicting that the effects of PGF deficiency identified in this model will be more severe than any effects in PE-offspring. WIDER IMPLICATIONS OF THE FINDINGS: These studies provoke the question of whether PGF expression is decreased and cerebral vascular maldevelopment occurs in fetuses who experience a preeclamptic gestation. These individuals have already been reported to have elevated risk for stroke and cognitive impairments. LARGE SCALE DATA: N/A. STUDY FUNDING AND COMPETING INTERESTS: This work was supported by awards from the Natural Sciences and Engineering Research Council, the Canada Research Chairs Program and the Canadian Foundation for Innovation to B.A.C. and by training awards from the Universidade Federal de Pernambuco and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil to R.L.L.; Queen's University to V.R.K. and the Canadian Institutes of Health Research to M.T.R. The work of P.C. is supported by the Belgian Science Policy BELSPO-IUAP7/03, Structural funding by the Flemish Government-Methusalem funding, and the Flemish Science Fund-FWO grants. There were no competing interests.

Brain vascular lesions: a clinicopathologic, immunohistochemistry, and ultrastructural approach.

Brain vascular malformations are relatively common lesions that cause serious neurologic disability or death in a significant proportion of individuals bearing them. The purpose of this study was to analyze the clinicopathologic and immunohistochemistry these lesions, looking for common antibodies expressed such as CD31, CD34, CD15, factor VIII, nestin, vimentin, vascular endothelial grow factor (VEGF), vascular endothelial grow factor receptor-2 (VEGF-R2), glial fibrillar acidic protien (GFAP), and fibroblastic grow factor ß (ß-FGF) and ultrastructure in endothelial cells as well as in vessel walls. Fifty cases of vascular lesions were included in this study: 29 (58%) of them were arteriovenous malformations and 21 (52%) were brain cavernomas. Twenty-six (52%) patients were women and 24 (48%) men. The age range was from 13 to 68 years (mean age, 35.86 ± 15.19 years). The size of the lesions ranged between 1 and 8 cm (3 ± 1.65 cm), and parieto-occipital lesions had a bigger size. Evolution time varied from 1 month to 1 year (mean, 7.5 months). There was a significant statistical correlation between age and sex (P = -035), rupture of lesion (P = .015), brain hemorrhage (P = .033), necrosis (P = .011), hemosiderin deposit (P = .042), VEGF (P = .015), and VEGFR (P = .037), as well as localization of rupture (P = .017), loss of consciousness (P = .000), visual deficit (P = .026), hyaline vessels (P = .000), and CD31 (.009). Interactions between endothelial cells and mural cells (pericytes and vascular smooth muscle cells) in blood vessel walls have recently come into focus as central processes in the regulation of vascular formation, stabilization, remodeling, and function in brain vascular lesions. However, the molecular mechanisms that underlie the formation and growth of brain arteriovenous malformations are still poorly understood.

Angiografia cerebral em cães / Cerebral angiography in dogs

Angiografia cerebral é o método de imagem empregado para detecção de alterações dos vasos sanguíneos do cérebro, pela injeção de contraste positivo e obtenção da imagem por meio da radiografia convencional, tomografia computadorizada ou ressonância magnética. No presente trabalho, descreve-se a técnica com o emprego da radiografia convencional em razão da disponibilidade muito restrita de equipamentos de tomografia computadorizada e da inexistência de equipamentos de ressonância magnética na área da medicina veterinária, no Brasil. O objetivo foi avaliar a eficácia do meio de imagem para demonstrar o padrão angiográfico de animais sem afecção neurológica, visando a preencher a lacuna deixada pelo exame radiográfico simples, em casos de alterações de fluxo sanguíneo intracranianos. Concluiu-se que a técnica utilizada é eficaz para a obtenção de imagens nítidas dos vasos cerebrais e sua distribuição.

Cerebral angiography is an imaging technique used to detect alterations in the blood supply of the brain. A positive contrast is injected and the image obtained by conventional radiography, computerized tomography or magnetic resonance (MRI). The present research describes the technique with the use of conventional radiography due to the rare availability of tomography or MRI equipment in veterinary practice. The objective was to evaluate the efficiency of the method in demonstrating the angiographic pattern of normal animals, to serve as a complementary exam to simple x-ray and improve the capability of detecting altered intracranial blood flow. It is concluded that the technique is capable of producing clear images of cerebral vessels and its ramifications.

Angiografia cerebral em cães

Cerebral angiography is an imaging technique used to detect alterations in the blood supply of the brain. A positive contrast is injected and the image obtained by conventional radiography, computerized tomography or magnetic resonance (MRI). The present research describes the technique with the use of conventional radiography due to the rare availability of tomography or MRI equipment in veterinary practice. The objective was to evaluate the efficiency of the method in demonstrating the angiographic pattern of normal animals, to serve as a complementary exam to simple x-ray and improve the capability of detecting altered intracranial blood flow. It is concluded that the technique is capable of producing clear images of cerebral vessels and its ramifications.

Angiografia cerebral é o método de imagem empregado para detecção de alterações dos vasos sanguíneos do cérebro, pela injeção de contraste positivo e obtenção da imagem por meio da radiografia convencional, tomografia computadorizada ou ressonância magnética. No presente trabalho, descreve-se a técnica com o emprego da radiografia convencional em razão da disponibilidade muito restrita de equipamentos de tomografia computadorizada e da inexistência de equipamentos de ressonância magnética na área da medicina veterinária, no Brasil. O objetivo foi avaliar a eficácia do meio de imagem para demonstrar o padrão angiográfico de animais sem afecção neurológica, visando a preencher a lacuna deixada pelo exame radiográfico simples, em casos de alterações de fluxo sanguíneo intracranianos. Concluiu-se que a técnica utilizada é eficaz para a obtenção de imagens nítidas dos vasos cerebrais e sua distribuição.

Angiografia cerebral em cães

Cerebral angiography is an imaging technique used to detect alterations in the blood supply of the brain. A positive contrast is injected and the image obtained by conventional radiography, computerized tomography or magnetic resonance (MRI). The present research describes the technique with the use of conventional radiography due to the rare availability of tomography or MRI equipment in veterinary practice. The objective was to evaluate the efficiency of the method in demonstrating the angiographic pattern of normal animals, to serve as a complementary exam to simple x-ray and improve the capability of detecting altered intracranial blood flow. It is concluded that the technique is capable of producing clear images of cerebral vessels and its ramifications.

Angiografia cerebral é o método de imagem empregado para detecção de alterações dos vasos sanguíneos do cérebro, pela injeção de contraste positivo e obtenção da imagem por meio da radiografia convencional, tomografia computadorizada ou ressonância magnética. No presente trabalho, descreve-se a técnica com o emprego da radiografia convencional em razão da disponibilidade muito restrita de equipamentos de tomografia computadorizada e da inexistência de equipamentos de ressonância magnética na área da medicina veterinária, no Brasil. O objetivo foi avaliar a eficácia do meio de imagem para demonstrar o padrão angiográfico de animais sem afecção neurológica, visando a preencher a lacuna deixada pelo exame radiográfico simples, em casos de alterações de fluxo sanguíneo intracranianos. Concluiu-se que a técnica utilizada é eficaz para a obtenção de imagens nítidas dos vasos cerebrais e sua distribuição.

Angiografia cerebral em cães

Cerebral angiography is an imaging technique used to detect alterations in the blood supply of the brain. A positive contrast is injected and the image obtained by conventional radiography, computerized tomography or magnetic resonance (MRI). The present research describes the technique with the use of conventional radiography due to the rare availability of tomography or MRI equipment in veterinary practice. The objective was to evaluate the efficiency of the method in demonstrating the angiographic pattern of normal animals, to serve as a complementary exam to simple x-ray and improve the capability of detecting altered intracranial blood flow. It is concluded that the technique is capable of producing clear images of cerebral vessels and its ramifications.

Angiografia cerebral é o método de imagem empregado para detecção de alterações dos vasos sanguíneos do cérebro, pela injeção de contraste positivo e obtenção da imagem por meio da radiografia convencional, tomografia computadorizada ou ressonância magnética. No presente trabalho, descreve-se a técnica com o emprego da radiografia convencional em razão da disponibilidade muito restrita de equipamentos de tomografia computadorizada e da inexistência de equipamentos de ressonância magnética na área da medicina veterinária, no Brasil. O objetivo foi avaliar a eficácia do meio de imagem para demonstrar o padrão angiográfico de animais sem afecção neurológica, visando a preencher a lacuna deixada pelo exame radiográfico simples, em casos de alterações de fluxo sanguíneo intracranianos. Concluiu-se que a técnica utilizada é eficaz para a obtenção de imagens nítidas dos vasos cerebrais e sua distribuição.