CSF pressure in fetal micein utero: External factors pressurize the intraventricular space

Previous experiments inducing leakage of embryonic cerebrospinal fluid (CSF) suggest the necessity of intraventricular CSF pressure (P CSF ) for brain morphogenesis. Nevertheless, how embryonic P CSF occurs is unclear, especially in utero . Using a Landis water manometer, we measured P CSF in fetal mice isolated from the amniotic cavity (P CSF-ISO ). At embryonic day (E) 13, P CSF-ISO was 82.7 Pa. Intraventricular injections of ≥2 μl of saline elevated P CSF-ISO by ∼30%. Intraventricularly injecting inhibitors of CSF secretion decreased P CSF-ISO by ∼30%. Shh-mediated cerebral-wall expansion and the resulting ventricular narrowing did not significantly increase P CSF-ISO . Removal of the brain-surrounding contractile tissues decreased P CSF-ISO by 80-90%. The intraamniotic pressure measured in utero (P AF-IU ) was 1030.7 Pa. Our direct measurement revealed that the P CSF in utero (P CSF-IU ) was 1076.4 Pa, confirming the susceptibility of P CSF to external factors. Subsequent P CSF measurements under hydrostatic pressure loading suggested that P CSF-IU = P CSF-ISO + P AF-IU , a relationship further used to estimate P CSF-IU at other ages when direct measurement was not possible. The estimated P CSF-IU decreased almost constantly from E10 to E16 (2000 ➔ 500 Pa).