| LDR | | 00000nam u2200205 4500 |
| 001 | | 000000434194 |
| 005 | | 20200226142213 |
| 008 | | 200131s2019 ||||||||||||||||| ||eng d |
| 020 | |
▼a 9781085708111 |
| 035 | |
▼a (MiAaPQ)AAI22587194 |
| 040 | |
▼a MiAaPQ
▼c MiAaPQ
▼d 247004 |
| 082 | 0 |
▼a 575 |
| 100 | 1 |
▼a Santhosh, Devi. |
| 245 | 10 |
▼a Brain Region Specific Neurovascular Signaling and Germinal Matrix Hemmorhage. |
| 260 | |
▼a [S.l.]:
▼b The University of Wisconsin - Madison.,
▼c 2019. |
| 260 | 1 |
▼a Ann Arbor:
▼b ProQuest Dissertations & Theses,
▼c 2019. |
| 300 | |
▼a 184 p. |
| 500 | |
▼a Source: Dissertations Abstracts International, Volume: 81-03, Section: B. |
| 500 | |
▼a Advisor: Huang, Zhen. |
| 502 | 1 |
▼a Thesis (Ph.D.)--The University of Wisconsin - Madison, 2019. |
| 506 | |
▼a This item must not be sold to any third party vendors. |
| 520 | |
▼a Vascular development in the brain is a complex and dynamic process closely coordinated with neural development. This necessitates, among other things, a close interaction between neural progenitors cells (NPCs), and endothelial cells (ECs). Communication between these cells allows NPCs to tightly regulate EC behavior to control the development of vessels that meet their high metabolic demands as well as providing protection for the brain. While several pathways have been well established as critical for generating this specialized network, G-protein coupled receptor (GPCR) signaling has still a ill-defined role in neurovascular development. Employing mouse genetics, we have found that in the germinal matrix (GM), NPCs use GPCRs to regulate endothelial TGF棺 signaling and the temporal dynamics of this pathway is functionally critical for GM blood vessel maturation. Using chemogenetics, we activated this GPCR pathway through Designer Receptors Activated by Designer Drugs (DREADDs) and discovered that premature activation of this pathway by the synthetic DREADD activator, CNO, caused detrimental effects on vessel growth. Excitingly, we also identified a specific dose and time of activation that improved vessel maturation in vivo. Similar experiments in a mouse model of Germinal Matrix Hemorrhage (GMH), a human disease prevalent in premature infants, also resulted in phenotypic rescue, providing clinically relevant information for medical intervention. These studies provide major new insight into mechanisms of neurovascular development and how this process may be differentially regulated in a region-specific manner and be harnessed for intervention in human diseases. |
| 590 | |
▼a School code: 0262. |
| 650 | 4 |
▼a Developmental biology. |
| 650 | 4 |
▼a Neurosciences. |
| 650 | 4 |
▼a Genetics. |
| 690 | |
▼a 0758 |
| 690 | |
▼a 0317 |
| 690 | |
▼a 0369 |
| 710 | 20 |
▼a The University of Wisconsin - Madison.
▼b Genetics. |
| 773 | 0 |
▼t Dissertations Abstracts International
▼g 81-03B. |
| 773 | |
▼t Dissertation Abstract International |
| 790 | |
▼a 0262 |
| 791 | |
▼a Ph.D. |
| 792 | |
▼a 2019 |
| 793 | |
▼a English |
| 856 | 40 |
▼u http://www.riss.kr/pdu/ddodLink.do?id=T15492977
▼n KERIS
▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
| 980 | |
▼a 202002
▼f 2020 |
| 990 | |
▼a ***1008102 |
| 991 | |
▼a E-BOOK |