Intracerebral Transplantation of Porcine Choroid Plexus Provides Structural and Functional Neuroprotection in a Rodent Model of Stroke

• DOI: 10.1161/01.str.0000138954.25825.0b
• Publication Date: 2004-07-30T00:27:30Z
• Authors: Cesar V. Borlongan; Steve J.M. Skinner; Marilyn Geaney; Alfred V. Vasconc...; Robert B. Elliott; Dwaine F. Emerich
• Keywords: Cerebral Cortex; Male; Cell Death; Alginates; Brain-Derived Neurotrophic Factor; Drug Compounding; Hexuronic Acids; Infarction, Middle Cerebral Artery; Cerebral Infarction; Motor Activity; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Animals, Newborn; Glucuronic Acid; Culture Media, Conditioned; Choroid Plexus; Animals; Brain Tissue Transplantation; Female; Glial Cell Line-Derived Neurotrophic Factor; Gliosis; Cells, Cultured

Background and Purpose—

Choroid plexus (CP) secretes a cocktail of neurotrophic factors. In the present study, CP from neonatal pigs was encapsulated within alginate microcapsules for in vitro and in vivo neuroprotective studies.

Methods—

In vitro studies involved serum deprivation of rat embryonic cortical neurons and treatment with a range of concentrations of conditioned media from CP. For in vivo studies, rats received a 1-hour middle cerebral artery occlusion followed by intracranial transplantation of encapsulated or unencapsulated CP, empty capsules, or no transplant. Behavioral testing was conducted on days 1 to 3 after transplantation. Cerebral infarction was analyzed using 2,3,5-triphenyl-tetrazolium chloride staining at 3 days after transplantation.

Results—

Conditioned media from CP produced a significant dose-dependent protection of serum-deprived cortical neurons. Enzyme-linked immunosorbent assay confirmed secretion of GDNF, BDNF, and NGF from CP. Parallel in vivo studies showed that CP transplants improved behavioral performance and decreased the volume of infarction. Both encapsulated and unencapsulated CP transplants were effective; however, more robust benefits accompanied encapsulated transplants.

Conclusions—

These data are the first to demonstrate the neuroprotective potential of transplanted CP and raise the intriguing possibility of using these cells as part of the treatment regimen for stroke and other neurological disorders.