Hydrocephalus induced by immunological blockage of the subcommissural organ-Reissner's fiber (RF) complex by maternal transfer of anti-RF antibodies

Stenosis of the cerebral aqueduct seems to be a key event for the developme nt of congenital hydrocephalus. The causes of such a stenosis are not well known. Overholser et al, in 1954 (Anat Rec 120:917-933) proposed the hypoth esis that a dysfunction of the subcommissural organ (SCO) leads to aqueduct al stenosis and congenital hydrocephalus. The SCO is a brain gland, located at the entrance of the cerebral aqueduct, that secretes glycoproteins into the cerebrospinal fluid that, upon release, assemble into a fibrous struct ure known as Reissner's fiber (RF). By the permanent addition of new molecu les to its rostral end, RF grows and extends along the aqueduct, fourth ven tricle, and central canal of the spinal cord. The immunological blockage of the SCO-RF complex has been used to test Overholser's hypothesis. The foll owing was the sequence of events occurring in pregnant rats that had been i mmunized with RF glycoproteins: the mother produced anti-RF antibodies and transferred them to the fetus through the placenta and to the pup through t he milk, and the antibodies reached the brain of the fetus and pup and bloc ked the SCO-RF complex. This resulted in a permanent absence of RF that was followed by stenosis of the cerebral aqueduct, and then by the appearance of hydrocephalus. The latter was patent until the end of the 6-month observ ation period. The chronic hydrocephalic state appeared, in turn, to induce new alterations of the SCO. It is concluded that a selective immunological knock out of the SCO-RF complex leads to hydrocephalus.