التفاصيل البيبلوغرافية
| العنوان: |
Neuronal GPR81 regulates developmental brain angiogenesis and promotes brain recovery after a hypoxic ischemic insult |
| المؤلفون: |
Chaudhari, Prabhas, Madaan, Ankush, Rivera, José Carlos, Charfi, Iness, Habelrih, Tiffany, Hou, Xin, Nezhady, Mohammad, Lodygensky, Gregory, Pineyro, Graciela, Muanza, Thierry, Chemtob, Sylvain |
| المصدر: |
Journal of Cerebral Blood Flow & Metabolism ; volume 42, issue 7, page 1294-1308 ; ISSN 0271-678X 1559-7016 |
| بيانات النشر: |
SAGE Publications |
| سنة النشر: |
2022 |
| الوصف: |
Perinatal hypoxic/ischemic (HI) brain injury is a major clinical problem with devastating neurodevelopmental outcomes in neonates. During HI brain injury, dysregulated factor production contributes to microvascular impairment. Glycolysis-derived lactate accumulated during ischemia has been proposed to protect against ischemic injury, but its mechanism of action is poorly understood. Herein, we hypothesize that lactate via its G-protein coupled receptor (GPR81) controls postnatal brain angiogenesis and plays a protective role after HI injury. We show that GPR81 is predominantly expressed in neurons of the cerebral cortex and hippocampus. GPR81-null mice displayed a delay in cerebral microvascular development linked to reduced levels of various major angiogenic factors and augmented expression of anti-angiogenic Thrombospondin-1 (TSP-1) in comparison to their WT littermates. Coherently, lactate stimulation induced an increase in growth factors (VEGF, Ang1 and 2, PDGF) and reduced TSP-1 expression in neurons, which contributed to accelerating angiogenesis. HI injury in GPR81-null animals curtailed vascular density and consequently increased infarct size compared to changes seen in WT mice; conversely intracerebroventricular lactate injection increased vascular density and diminished infarct size in WT but not in GPR81-null mice. Collectively, we show that lactate acting via GPR81 participates in developmental brain angiogenesis, and attenuates HI injury by restoring compromised microvasculature. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1177/0271678x221077499 |
| DOI: |
10.1177/0271678X221077499 |
| الإتاحة: |
https://doi.org/10.1177/0271678x221077499Test |
| حقوق: |
http://journals.sagepub.com/page/policies/text-and-data-mining-licenseTest |
| رقم الانضمام: |
edsbas.594B4FE2 |
| قاعدة البيانات: |
BASE |
