Intracerebral transplantation of porcine choroid plexus provides structural and functional neuroprotection in a rodent model of stroke.
OBJECTIVE
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.
Department of Neurology, School of Medicine, and the Institute of Molecular Medicine and Genetics, School of Graduate Studies, Medical College of Georgia, Augusta, Ga 30912-3200, USA. cborlongan@mail.mcg.edu
Cesar V
CV
Borlongan
Steve J M
SJ
Skinner
Marilyn
M
Geaney
Alfred V
AV
Vasconcellos
Robert B
RB
Elliott
Dwaine F
DF
Emerich
D000464:Alginates; D000818:Animals; D000831:Animals, Newborn; D016380:Brain Tissue Transplantation; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D016923:Cell Death; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology; D002831:Choroid Plexus / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004339:Drug Compounding; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005911:Gliosis / Q000209:etiology; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000601:surgery*; D008297:Male; D009043:Motor Activity; D020932:Nerve Growth Factor / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D034421:Sus scrofa; D014183:Transplantation, Heterologous; D016042:Transplantation, Heterotopic
D000464:Alginates; D019208:Brain-Derived Neurotrophic Factor; D017077:Culture Media, Conditioned; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006603:Hexuronic Acids; D009414:Nerve Growth Factors; D020723:Glucuronic Acid; D020932:Nerve Growth Factor