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Vascular endothelial growth factor mediates reactive angiogenesis in the postnatal developing brain
L R Ment1, W B Stewart, R Fronc
1Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06510, USA.
Brain Research. Developmental Brain Research
|May 20, 1997
Summary
Chronic hypoxia promotes brain angiogenesis and vessel permeability in developing rats. Vascular endothelial growth factor (VEGF) appears to mediate this response, as shown by increased VEGF levels and in vitro angiogenesis.
Area of Science:
- Neuroscience
- Developmental Biology
- Physiology
Background:
- Chronic sublethal hypoxia is known to promote angiogenesis in the developing brain.
- The precise mechanisms underlying this angiogenic response remain largely unknown.
Purpose of the Study:
- To investigate the role of vascular endothelial growth factor (VEGF) in mediating the angiogenic response to chronic hypoxia in the developing brain.
- To examine the effects of hypoxia on brain vascular density, permeability, and VEGF expression in vivo and in vitro.
Main Methods:
- Newborn rats were exposed to chronic hypoxia (9.5% O2) from P3 to P33.
- Brain tissue was analyzed for vascular density, vessel permeability (using HRP), and VEGF mRNA and protein levels.
- In vitro studies involved co-culturing beagle brain microvascular endothelial cells (BBMEC) with rat astrocytes under hypoxic conditions (11% O2).
- VEGF's direct effect on endothelial cell proliferation and tube formation was assessed.
Main Results:
- Hypoxic rats exhibited significantly increased cortical vascular density and enhanced cortical vessel permeability compared to controls.
- VEGF mRNA levels were 2.4-fold higher in hypoxic pups, with corresponding increases in VEGF protein.
- In vitro, hypoxic co-cultures showed increased tube formation, and astrocyte VEGF protein levels increased 4.4-fold.
- Exogenous VEGF administration stimulated BBMEC proliferation and tube formation.
Conclusions:
- The developing brain responds to chronic sublethal hypoxia with increased vascular permeability and angiogenesis.
- Vascular endothelial growth factor (VEGF) plays a critical role in mediating these hypoxia-induced angiogenic responses in the developing brain.