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Comparison of vascular growth factors in the murine brain reveals placenta growth factor as prime candidate for CNS revascularization
Comparison of vascular growth factors in the murine brain reveals placenta growth factor as prime candidate for CNS revascularization
- Source :
- Blood
- Publication Year :
- 2013
- Publisher :
- American Society of Hematology, 2013.
-
Abstract
- Vascular bypass procedures in the central nervous system (CNS) remain technically challenging, hindered by complications and often failing to prevent adverse outcome such as stroke. Thus, there is an unmet clinical need for a safe and effective CNS revascularization. Vascular endothelial growth factors (VEGFs) are promising candidates for revascularization; however, their effects appear to be tissue-specific and their potential in the CNS has not been fully explored. To test growth factors for angiogenesis in the CNS, we characterized the effects of endothelium-specific growth factors on the brain vasculature and parenchyma. Recombinant adeno-associated virus (AAV) vectors encoding the growth factors were injected transcranially to the frontoparietal cerebrum of mice. Angiogenesis, mural cell investment, leukocyte recruitment, vascular permeability, reactive gliosis and neuronal patterning were evaluated by 3-dimensional immunofluorescence, electron microscopy, optical projection tomography, and magnetic resonance imaging. Placenta growth factor (PlGF) stimulated robust angiogenesis and arteriogenesis without significant side effects, whereas VEGF and VEGF-C incited growth of aberrant vessels, severe edema, and inflammation. VEGF-B, angiopoietin-1, angiopoietin-2, and a VEGF/angiopoietin-1 chimera had minimal effects on the brain vessels or parenchyma. Of the growth factors tested, PlGF emerged as the most efficient and safe angiogenic factor, hence making it a candidate for therapeutic CNS revascularization.
- Subjects :
- Central Nervous System
Vascular Endothelial Growth Factor A
Pathology
medicine.medical_specialty
Angiogenesis
medicine.medical_treatment
Vascular Endothelial Growth Factor C
Immunology
Neovascularization, Physiologic
Cerebral Revascularization
Pregnancy Proteins
Revascularization
Biochemistry
Mural cell
Central Nervous System Neoplasms
Neovascularization
Mice
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Placenta Growth Factor
030304 developmental biology
0303 health sciences
business.industry
Growth factor
Genetic Therapy
Cell Biology
Hematology
3. Good health
Mice, Inbred C57BL
Vascular endothelial growth factor A
Vascular endothelial growth factor C
Blood Vessels
Encephalitis
Intercellular Signaling Peptides and Proteins
Female
medicine.symptom
Hemangioma
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 122
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....b41205344386741471df59e0b590479c
- Full Text :
- https://doi.org/10.1182/blood-2012-07-441527