Abstract 389: Gestational Inflammation and Perinatal Arterial Ischemic Stroke: A Causal Connection?
Introduction: Perinatal arterial ischemic strokes affect about 1/3,000 newborn and are the main cause of hemiplegic cerebral palsy. The large cerebral arteries from the anterior system, namely the intra-cranial carotid bifurcation, are the most affected, ischemic stroke being located in its territory in 85% of cases. The classic, but unproven, pathophysiological hypothesis postulated that arterial occlusion was caused by emboli from placental origin. This remains controversial due to the major unbalance of brain infarcts between anterior and posterior distribution, and to the absence of associated extra-cerebral infarcts. A new pathophysiological perspective emerged from the epidemiological association between gestational inflammation and perinatal stroke. Our hypothesis is that materno-foetal inflammation, induced by gestational exposure to pathogens, leads to a site-specific vasculitis affecting the carotid bifurcation and then triggering a focal thrombosis.
Material and methods: Dams were injected with saline or lipopolysaccharide (LPS) from Escherichia coli (200 μg/kg/12h) between gestational day (G) 21 and 22. Brains were harvested at G21, G22 and postnatal day 1 (P1). At P1, a prothrombotic stress (transcutaneous photothrombosis) was applied on middle cerebral arteries to compare its susceptibility to thrombosis between LPS-exposed or unexposed pups. Immunohistochemistry and ELISA detected maternal, placental and fetal/neonatal inflammatory markers.
Results: Our results showed a maternal, placental and fetal inflammation mediated by IL-1β, TNF-α and MCP-1 as well as an arterial inflammation in relation with the clinical pattern of perinatal arterial ischemic strokes. LPS+photothrombosis pups presented ischemic strokes and motor impairments, which were not detected when photothrombosis was applied without prior treatment with LPS.
Conclusion: Preliminary results from our new pre-clinical model support our hypothesis of increased susceptibility of anterior cerebral arteries to gestational inflammation, and open a new vasculitic pathophysiological avenue to understand perinatal stroke.
Author Disclosures: C. Guiraut: None. N. Cauchon: None. M. Lepage: None. G. Sebire: None.
- © 2014 by American Heart Association, Inc.