Title: Role of tissue-derived plasminogen activator (t-PA) in an excitotoxic mouse model of neonatal white matter lesions
Authors: Hennebert, Olivier ×
Marret, Stéphane
Carmeliet, Peter
Gressens, Pierre
Laquerrière, Annie
Leroux, Philippe #
Issue Date: Jan-2004
Series Title: Journal of Neuropathology and Experimental Neurology vol:63 issue:1 pages:53-63
Abstract: White matter (WM) lesions in preterm newborns may lead to cerebral palsy. To study WM lesions in a mouse model, we used intrapallial stereotactic injections of ibotenic acid, an N-methyl-D-aspartate receptor agonist. Previous studies support a contribution of tissue-type plasminogen activator (t-PA) to the brain lesions seen in various adult excitotoxic models. Therefore, we studied both 5-day-old (P5) wild-type mice and t-PA knock-out (t-PA-/-) mice. The ibotenic acid doses required to induce WM cysts were lower in the wild-type mice (EC50 < 0.01 microg/animal) than in the t-PA-/- mice (EC50 = 2.5 microg/animal) (p < 0.01), indicating the existence of t-PA-dependent and t-PA-independent mechanisms. Dose-dependent prolonged cyst growth occurred in the wild-type mice only. Early microglial activation and astrogliosis were similar in the wild-type and t-PA-/- mice. In adult mice (P45), demyelination occurred at the injection site in both groups but the astroglial scar was denser in the wild-type than in the t-PA-/- mice. These data support involvement of t-PA at several stages of WM lesion formation. Inactivation of t-PA might confer protection by prolonged hemostasis. The role of t-PA in cyst expansion suggests a new approach to the development of neuroprotective strategies in infants with developing WM lesions.
ISSN: 0022-3069
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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