| First Author | Schumacher S | Year | 2024 |
| Journal | Glia | Volume | 72 |
| Issue | 1 | Pages | 34-50 |
| PubMed ID | 37670489 | Mgi Jnum | J:343521 |
| Mgi Id | MGI:7565948 | Doi | 10.1002/glia.24460 |
| Citation | Schumacher S, et al. (2024) Inhibiting astrocyte connexin-43 hemichannels blocks radiation-induced vesicular VEGF-A release and blood-brain barrier dysfunction. Glia 72(1):34-50 |
| abstractText | Therapeutic brain irradiation with ionizing radiation exerts multiple side effects including barrier leakage that disturbs glial-neuronal functioning and may affect cognition. Astrocytes contribute to barrier leakage by endfeet release of various vasoactive substances acting on capillary endothelial cells forming the barrier. Here, we investigated X-ray effects on astrocytic vesicular transport in mice and determined whether interfering with astrocyte connexins affects radiation-induced barrier leakage. We found that astrocytic VEGF-A-loaded VAMP3 vesicles drastically reorganize starting from 6 h post-irradiation and move in a calcium- and Cx43-dependent manner towards endfeet where VEGF-A is released, provoking barrier leakage. Vesicular transport activation, VEGF-A release and leakage 24 h post-irradiation were all potently inhibited by astrocytic Cx43 KO, Cx43S255/262/279/282A (MK4) mutant mice and TATGap19 inhibition of Cx43 hemichannel opening. Astrocyte VEGF release is a major player in complications of brain irradiation, which can be mitigated by anti-VEGF treatments. Targeting Cx43 hemichannels allows to prevent astrocyte VEGF release at an early stage after brain irradiation. |
