| First Author | Lummis NC | Year | 2019 |
| Journal | Sci Adv | Volume | 5 |
| Issue | 10 | Pages | eaax2011 |
| PubMed ID | 31633020 | Mgi Jnum | J:288682 |
| Mgi Id | MGI:6429994 | Doi | 10.1126/sciadv.aax2011 |
| Citation | Lummis NC, et al. (2019) LPA1/3 overactivation induces neonatal posthemorrhagic hydrocephalus through ependymal loss and ciliary dysfunction. Sci Adv 5(10):eaax2011 |
| abstractText | Posthemorrhagic hydrocephalus (PHH) in premature infants is a common neurological disorder treated with invasive neurosurgical interventions. Patients with PHH lack effective therapeutic interventions and suffer chronic comorbidities. Here, we report a murine lysophosphatidic acid (LPA)-induced postnatal PHH model that maps neurodevelopmentally to premature infants, a clinically accessible high-risk population, and demonstrates ventriculomegaly with increased intracranial pressure. Administration of LPA, a blood-borne signaling lipid, acutely disrupted the ependymal cells that generate CSF flow, which was followed by cell death, phagocytosis, and ventricular surface denudation. This mechanism is distinct from a previously reported fetal model that induces PHH through developmental alterations. Analyses of LPA receptor-null mice identified LPA1 and LPA3 as key mediators of PHH. Pharmacological blockade of LPA1 prevented PHH in LPA-injected animals, supporting the medical tractability of LPA receptor antagonists in preventing PHH and negative CNS sequelae in premature infants. |
