Paradoxical rise in brainstem PO(2) following umbilical cord occlusion in full-term rat fetuses.

Although the fetus experiences severe hypoxia and ischemia during delivery, the fetal brain is protected from hypoxic-ischemic insults by unknown mechanisms. To investigate this phenomenon, fetal asphyxia was induced in pregnant rats by occlusion of the umbilical cord. Rather than producing cerebral hypoxia, the brainstem PO(2) of at-term fetuses increased following umbilical cord occlusion, while brainstem blood flow was markedly reduced. This paradoxical increase in brainstem PO(2) during asphyxia occurred in the majority of at-term fetuses, less frequently in fetuses 1 day prior to term and did not occur in animals following birth. Because occlusion of the umbilical cord prevents maternal delivery of oxygen to the fetus, we propose that the ability to maintain PO(2) is the result of pre-existing fetal stores of oxygen or from de novo generation of oxygen in the fetal brainstem.

Asphyxia induced by umbilical cord occlusion alters glutamatergic and GABAergic synaptic transmission in neurons of the superior colliculus in fetal rats.

Using optical recordings, we studied the effects of asphyxia on intracellular Cl(-) and Ca(2+) concentrations ([Cl(-)]i; [Ca(2+)]i) in the superior colliculus of fetal rats, which were connected via the umbilical cord to the dam. Acute asphyxia was induced by umbilical cord occlusion. The number of fetal superior colliculus neurons showing GABA-mediated increases in [Cl(-)]i (leading to hyperpolarization) following local synaptic electrical stimulation had decreased by 3 h post-asphyxiation, while the number showing GABA-mediated decreases in [Cl(-)]i (leading to depolarization) increased. [Ca(2+)]i rise, which occurred after acute asphyxiation, was antagonized by both non-NMDA and NMDA receptor antagonists. The increase in [Ca(2+)]i following focal superior colliculus stimulation was markedly attenuated at 3 h post-asphyxiation. These findings suggest that asphyxia induced by umbilical occlusion induces changes in glutamatergic and GABAergic synaptic transmission in the fetal brain.

Stimulation of fetal hypothalamus induces uterine contractions in pregnant rats at term.

The fetal brain is thought to have a role in the onset and progression of labor. Evidence also exists for fetal oxytocin release just before and during parturition. The present study examined whether activation of the fetal brain could induce uterine myometrial contractions through oxytocin receptors in the dam. Under urethane anesthesia, electrical stimulation of the hypothalamus of fetal rats that were still connected with the dams by an intact umbilical cord induced uterine contractions in term pregnant rats. Intraperitoneal injections of synthetic oxytocin in fetuses induced uterine contractions in the dams similar to those induced by electrical stimulation of the fetal hypothalamus. Maternal intravenous injections of an oxytocin antagonist immediately attenuated uterine contractions induced by fetal oxytocin injections and electrical stimulation of the fetal hypothalamus. These findings suggest the possibility that oxytocin released from the fetal hypothalamus is involved in parturition.

In vivo optical recordings of synaptic transmission and intracellular Ca2+ and Cl- in the superior colliculus of fetal rats.

Although the N-methyl-D-aspartate (NMDA) receptor is known to play a crucial role in activity-dependent remodeling of synaptic connections in the fetal superior colliculus (SC), its contribution to the electrical activity of fetal SC neurons has not been determined. Furthermore, whether gamma-aminobutyric acid (GABA)-mediated inhibition occurs either as early as prenatal periods or only after eye opening has been controversial. We therefore performed optical recordings using voltage-, Ca2+- and Cl--sensitive fluorescent dyes to analyse synaptic transmission and changes in intracellular Ca2+ and Cl- in the SC of fetal rats that were still connected with the dams by the umbilical cord. Excitatory and inhibitory responses were evoked by focal SC stimulation. The excitatory synaptic responses are composed of early and late components. The early component was mediated by both non-NMDA and NMDA receptors, whereas the late component occurred mainly via NMDA receptors. Train pulse stimulation at higher currents was required for induction of the inhibition, which was antagonized by bicuculline, and blocking of the GABA-mediated inhibition by bicuculline uncovered masked excitatory synaptic responses. Focal SC stimulation induced increases in [Cl-]i and [Ca2+]i that were mediated by GABA-A receptors and mainly by NMDA receptors, respectively. GABA antagonists augmented SC-induced increases in [Ca2+]i. These results indicate that, in the fetal SC, excitatory and inhibitory synaptic transmissions occur before birth, that the NMDA receptor is a major contributor to excitatory synaptic transmission and increased [Ca2+]i, and that the GABA-A receptor is already functioning to inhibit excitatory neurotransmission.