Widespread Striatal Delivery of GDNF from Encapsulated Cells Prevents the Anatomical and Functional Consequences of Excitotoxicity

Methods. Human ARPE-19 cells engineered to secrete high levels of the glial cell line-derived neurotrophic factor (GDNF) were encapsulated into hollow fiber membranes. The devices were implanted into the rat striatum 1 week prior to striatal quinolinic acid injections. Animals were evaluated using a...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	Neural plasticity Ročník 2019; číslo 2019; s. 1 - 9
Hlavní autoři:	Wahlberg, Lars U., Bintz, Briannan, Thanos, Chris, Chu, Yaping, Kordower, Jeffrey H., Emerich, Dwaine F., Paolone, Giovanna
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Cairo, Egypt Hindawi Publishing Corporation 01.01.2019 Hindawi John Wiley & Sons, Inc Wiley
Témata:	Animals Brain Cell adhesion & migration Cell Encapsulation Cell Line Corpus Striatum - drug effects Drug Delivery Systems Gene expression Glial Cell Line-Derived Neurotrophic Factor - administration & dosage Humans Humidity Immunology LLC-PK1 Cells Male Morphology Neurodegenerative Diseases - drug therapy Neurons - drug effects Neuroprotective Agents - administration & dosage Quinolinic Acid - toxicity Rats, Sprague-Dawley Scanning electron microscopy Skin Swine Denmark
ISSN:	2090-5904, 1687-5443, 1687-5443
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	Methods. Human ARPE-19 cells engineered to secrete high levels of the glial cell line-derived neurotrophic factor (GDNF) were encapsulated into hollow fiber membranes. The devices were implanted into the rat striatum 1 week prior to striatal quinolinic acid injections. Animals were evaluated using a battery of validated motor tests, and histology was performed to determine the extent of GDNF diffusion and associated prevention of neuronal cell loss and behavioral deficits. Results. Encapsulated cell-based delivery of GDNF produced widespread distribution of GDNF throughout the entire implanted striatum. Stereological estimates of striatal neuron number and volume of lesion size revealed that GDNF delivery resulted in near complete neuroprotection. Conclusions. Delivery of neurotrophic molecules such as GDNF using encapsulated cells has reached a technological point where clinical evaluation is justified. Because GDNF has been effective in animal models of Parkinson’s disease, stroke, epilepsy, and Huntington’s disease, among other debilitating neurodegenerative diseases, encapsulated cell-based delivery of GDNF might represent one innovative means of slowing the neural degeneration seen in a myriad of currently untreatable neurological diseases.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Guest Editor: Jolanta Dorszewska
ISSN:	2090-5904 1687-5443 1687-5443
DOI:	10.1155/2019/6286197