In rodent models, leukemia inhibitory factor (LIF) is involved in cerebral development via the placenta, and maternal immune activation is linked to psychiatric disorders in the child. However, whether LIF acts directly on neural progenitor cells (NPCs) remains unclear. This study performed DNA microarray analysis and quantitative RT-PCR on the fetal cerebrum after maternal intraperitoneal or fetal intracerebral ventricular injection of LIF at day 14.5 (E14.5) and determined that the expression of insulin-like growth factors (IGF)-1 and -2 was induced by LIF. Physiological IGF-1 and IGF-2 levels in fetal cerebrospinal fluid (CSF) increased from E15.5 to E17.5, following the physiological surge of LIF levels in CSF at E15.5. Immunostaining showed that IGF-1 was expressed in the cerebrum at E15.5 to E19.5 and IGF-2 at E15.5 to E17.5 and that IGF-1 receptor and insulin receptor were co-expressed in NPCs. Further, LIF treatment enhanced cultured NPC proliferation, which was reduced by picropodophyllin, an IGF-1 receptor inhibitor, even under LIF supplementation. Our findings suggest that IGF expression and release from the NPCs of the fetal cerebrum in fetal CSF is induced by LIF, thus supporting the involvement of the LIF–IGF axis in cerebral cortical development in an autocrine/paracrine manner.

A 54-year-old man presented with gait disturbances, urinary incontinence, and headache for 6 months. Head computed tomography indicated several high-density mass lesions in the quadrigeminal cistern, causing occlusive hydrocephalus. Digital subtraction angiography confirmed tentorial dural arteriovenous fistulae (AVF). Transarterial embolization (TAE) achieved complete angiographic resolution. However, acute occlusive hydrocephalus worsened, necessitating endoscopic third ventriculostomy (ETV). The patient was discharged without new symptoms and no hydrocephalus recurrence at six-month follow-up. Hydrocephalus is rare in patients with dural AVF and mostly resolves spontaneously after treatment; however, if thrombosis and enlargement of the varix occur after treatment, acute occlusive hydrocephalus can develop.