Embryonic cerebrospinal fluid pressure in fetal mice in utero: External factors pressurize the intraventricular space.

BACKGROUND

Previous experiments inducing leakage of embryonic cerebrospinal fluid (CSF) suggest the necessity of intraventricular CSF pressure (P) for brain morphogenesis. Nevertheless, how embryonic P occurs is unclear, especially in utero.

RESULTS

Using a Landis water manometer, we measured P in fetal mice isolated from the amniotic cavity (P) and found that P rose from 20 Pa at embryonic day (E) 10 to 100-110 Pa at E14-16. At E13, intraventricular injections of ≥3 μL of saline elevated P by ~30%, whereas those of inhibitors of CSF secretion decreased P by ~30%. Shh-mediated cerebral wall expansion did not significantly increase P. Removal of the brain-surrounding contractile tissues decreased P by 80%-90%. We then found that the intraamniotic pressure measured in utero (P) declined from 2000 Pa at E10 to 500 Pa at E15-18 but was always much greater than P. Direct measurement of P in utero (P) at E13 and E15 coupled with the measurement of P under hydrostatic pressure loading to mimic P at various embryonic ages revealed the following relationship: P = P + P.

CONCLUSIONS

The P of mice in utero is influenced by external factors, most strongly by intraamniotic pressure and less strongly by brain-confining tissues.