Organ Culture and Grafting of Choroid Plexus into the Ventricular CSF of Normal and Hydrocephalic HTx Rats.

Choroid plexus (CP) may aid brain development and repair by secreting growth factors and neurotrophins for CSF streaming to ventricular and subventricular zones. Disrupted ventricular/subventricular zone progenitors and stem cells lead to CNS maldevelopment. Exploring models, we organ cultured the CP and transplanted fresh CP into a lateral ventricle of postnatal hydrocephalic (hyHTx) and nonhydrocephalic (nHTx) rats. After 60 days in vitro, the cultured choroid ependyma formed spherical rings with beating cilia. Cultured CP expressed endocytotic caveolin 1 and apical aquaporin 1 and absorbed horseradish peroxidase from medium. Transthyretin secretory protein was secreted by organ-cultured CP into medium throughout 60 days in vitro. Fresh CP, surviving at 1 week after lateral ventricle implantation of nHTx or hyHTx did not block CSF flow. Avascular 1-week transplants in vivo expressed caveolin 1, aquaporin 1, and transthyretin, indicating that grafted CP may secrete trophic proteins but not CSF. Our findings encourage further exploration on CP organ culture and grafting for translational strategies. Because transplanted CP, though not producing CSF, may secrete beneficial molecules for developing brain injured by hydrocephalus, we propose that upon CP removal in hydrocephalus surgery, the fractionated tissue could be transplanted back (ventricular autograft).

Cell Junction Pathology of Neural Stem Cells Is Associated With Ventricular Zone Disruption, Hydrocephalus, and Abnormal Neurogenesis.

Fetal-onset hydrocephalus affects 1 to 3 per 1,000 live births. It is not only a disorder of cerebrospinal fluid dynamics but also a brain disorder that corrective surgery does not ameliorate. We hypothesized that cell junction abnormalities of neural stem cells (NSCs) lead to the inseparable phenomena of fetal-onset hydrocephalus and abnormal neurogenesis. We used bromodeoxyuridine labeling, immunocytochemistry, electron microscopy, and cell culture to study the telencephalon of hydrocephalic HTx rats and correlated our findings with those in human hydrocephalic and nonhydrocephalic human fetal brains (n = 12 each). Our results suggest that abnormal expression of the intercellular junction proteins N-cadherin and connexin-43 in NSC leads to 1) disruption of the ventricular and subventricular zones, loss of NSCs and neural progenitor cells; and 2) abnormalities in neurogenesis such as periventricular heterotopias and abnormal neuroblast migration. In HTx rats, the disrupted NSC and progenitor cells are shed into the cerebrospinal fluid and can be grown into neurospheres that display intercellular junction abnormalities similar to those of NSC of the disrupted ventricular zone; nevertheless, they maintain their potential for differentiating into neurons and glia. These NSCs can be used to investigate cellular and molecular mechanisms underlying this condition, thereby opening the avenue for stem cell therapy.