Harnessing region-specific neurovascular signaling to promote germinal matrix vessel maturation and hemorrhage prevention [RESEARCH ARTICLE]

In this study, we use mice to test whether this regional pathway can be harnessed for GMH intervention. We first examined the endogenous dynamics of this pathway and found that it displays specific patterns of activation. We then investigated the functional effects of altering these dynamics by chemogenetics and found that there is a narrow developmental window during which this pathway is amenable to manipulation. Although high-level activity in this time window interferes with vessel growth, moderate enhancement promotes vessel maturation without compromising growth. Furthermore, we found that enhancing the activity of this pathway in a mouse model rescues all GMH phenotypes. Altogether, these results demonstrate that enhancing neurovascular signaling through pharmacological targeting of this pathway may be a viable approach for tissue-specific GMH intervention. They also demonstrate that timing and level are likely two major factors crucial for success. These findings thus provide critical new insights into both brain neurovascular biology and the intervention of GMH.

Source: DMM Disease Models and Mechanisms - November 10, 2019 Category: Biomedical Science Authors: Santhosh, D., Sherman, J., Chowdhury, S., Huang, Z. Tags: RESEARCH ARTICLE Source Type: research