| First Author | Leroux P | Year | 2007 |
| Journal | Neuroscience | Volume | 146 |
| Issue | 2 | Pages | 670-8 |
| PubMed ID | 17321054 | Mgi Jnum | J:122015 |
| Mgi Id | MGI:3712997 | Doi | 10.1016/j.neuroscience.2007.01.029 |
| Citation | Leroux P, et al. (2007) Role of tissue-plasminogen activator (t-PA) in a mouse model of neonatal white matter lesions: interaction with plasmin inhibitors and anti-inflammatory drugs. Neuroscience 146(2):670-8 |
| abstractText | Ibotenic acid injected intracerebrally over a broad dose range to 5-day-old mice induces cystic white matter (WM) lesions that mimic periventricular leukomalacia (PVL) of preterm infants. With both low (0.1 mug) and high (5 mug) ibotenic acid doses, tissue-plasminogen activator (t-PA) is involved in cyst formation. Subsequent cyst growth depends on high doses. We evaluated the effects of human recombinant tissue-plasminogen activator (hrt-PA), plasmin inhibitors (tranexamic acid, alpha2-antiplasmin, and aprotinin), and anti-inflammatory drugs (betamethasone, NS-398) in wild-type and t-PA(-/-) mice given high-dose or low-dose ibotenic acid. Intracerebral hrt-PA induced WM cystic lesions in t-PA(-/-) mice and had an additive effect when co-injected with high-dose ibotenic acid. Plasmin inhibitors reduced lesion growth in wild-type mice given high-dose, but not low-dose, ibotenic acid but had no effect in t-PA(-/-) mice. Similarly the anti-inflammatory drugs betamethasone and NS-398 (a cyclooxygenase 2 and NFkappaB inhibitor) were neuroprotective in wild-type animals exposed to high-dose, but not low-dose, ibotenic acid. Thus, the t-PA-dependent effect of low-dose ibotenic acid on cyst formation appeared independent from plasmin activity or inflammation. Conversely, a t-PA-dependent inflammatory process occurred with high-dose ibotenic acid. Potential strategies for PVL in preterm neonates may include fibrinolytic monitoring for prevention and anti-inflammatory agents for treatment. |
