Title: De novo expression of Trpm4 initiates secondary hemorrhage in spinal cord injury
Authors: Gerzanich, Volodymyr
Woo, S. Kyoon
Vennekens, Rudi
Tsymbalyuk, Orest
Ivanova, Svetlana
Ivanov, Alexander
Geng, Zhihua
Chen, Zheng
Nilius, Bernd
Flockerzi, Veit
Freichel, Marc
Simard, J. Marc # ×
Issue Date: Feb-2009
Publisher: Nature publishing group
Series Title: Nature Medicine vol:15 issue:2 pages:185-191
Abstract: The role of transient receptor potential M4 (Trpm4), an unusual member of the Trp family of ion channels, is poorly understood. Using rodent models of spinal cord injury, we studied involvement of Trpm4 in the progressive expansion of secondary hemorrhage associated with capillary fragmentation, the most destructive mechanism of secondary injury in the central nervous system. Trpm4 mRNA and protein were abundantly upregulated in capillaries preceding their fragmentation and formation of petechial hemorrhages. Trpm4 expression in vitro rendered COS-7 cells highly susceptible to oncotic swelling and oncotic death following ATP depletion. After spinal cord injury, in vivo gene suppression in rats treated with Trpm4 antisense or in Trpm4(-/-) mice preserved capillary structural integrity, eliminated secondary hemorrhage, yielded a threefold to fivefold reduction in lesion volume and produced a substantial improvement in neurological function. To our knowledge, this is the first example of a Trp channel that must undergo de novo expression for manifestation of central nervous system pathology.
ISSN: 1078-8956
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Ion Channel Research
Department of Cellular and Molecular Medicine - miscellaneous
× corresponding author
# (joint) last author

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