The hypothalamus from a hydrocephalic brain showing an enlarged third ventricle (3V) and darkly-stained GnRH axons projecting to the pituitary gland.

A significant number of children, whose hydrocephalus has been treated successfully by shunting, develop reproductive problems, namely precocious (early) puberty and amenorrhea (absent or abnormal cycling).

The cause of these problems is unknown, but it is likely, since the third ventricle is surrounded by the region of the brain (hypothalamus) that controls the pituitary gland, that the initial insult occurs in the hypothalamus. To test this possibility directly, one of our Neurosurgery residents, Ramin M. Abdolvahabi, M.D., Ph.D., conducted a comprehensive analysis of the morphology and biochemistry of the hypothalamus in animals with congenital hydrocephalus.

At higher magnification than the previous figure, individual GnRH axons can be seen coursing through the hypothalamus to the surface of the brain.

To our surprise, he showed that the neurons that make GnRH (gonadotropin releasing hormnone, the protein that controls the secretion of reproductive hormones from the pituitary gland) were not dramatically affected structurally until very late stages of hydrocephalus. In contrast, the levels of GnRH in the hypothalamus were increased 10-fold, and were also associated with increased blood levels of luteinizing hormone (LH, the pituitary hormone that acts directly on the ovaries and testes).

These changes correlated with reproductive function, and could only be reversed if the shunts were working properly. Further studies will now be directed toward understanding how regulation of the GnRH system is influenced by hydrocephalus.