Monday, February 19, 2018

i-Fect Delivers siRNA to Study Angiogenesis in Brain Injury

Silencing Lactate Dehydrogenase A in vivo

Pathologic CNS is characterized by neuronal damage that leads to the release of intracellular components. However, the effect of damaged cells on angiogenesis has not been clarified. This study revealed that LDHA, which is a known damage marker, promotes CNS-specific angiogenesis. LDHA-mediated angiogenesis depends on vimentin on the surface of vascular endothelial cells. The work described here proposes a novel mechanism by which neurodegeneration drives angiogenesis in the CNS.

A mixture of our i-FectTM and LDHA siRNA, in this study, were directly injected into mice cortexes: Hsiaoyun Lin, Rieko Muramatsu, Noriko Maedera, Hiroto Tsunematsu, Machika Hamaguchi, Yoshihisa Koyama, Mariko Kuroda, Kenji Ono, Makoto Sawada, Toshihide Yamashita. Extracellular Lactate Dehydrogenase A Release From Damaged Neurons Drives Central Nervous System Angiogenesis. doi.org/10.1016/j.ebiom.2017.10.033.
Images: LDHA is sufficient to evoke CNS angiogenesis. (a) Representative images of CD105-labeled spinal cord sections obtained 7 days after LDHA administration. (b) Length of CD105+ neovessels around the LDHA administration site as indicated in a, n = 5 each. (c) Representative image of a Nissl-stained brain section after controlled cortical impact (CCI). (d) Representative image of the CD105-immunolabelled cerebral cortex obtained 7 days after CCI. (e) Length of CD105+ neovessels around CCI lesions as indicated in d; n = 5 each, all error bars represent the s.e.m. **P < 0.01, Student's t-tests. Scale bars, 200 μm.

The findings reveal unexpected neurovascular interactions in the injured adult CNS that may be relevant to our understanding of neuronal damage, which is a hallmark of many CNS disorders