Injectable hydrogels providing sustained delivery of vascular endothelial growth factor are neuroprotective in a rat model of Huntington's disease.
Vascular endothelial growth factor (VEGF) is a potent peptide with well-documented pro-angiogenic effects. Recently, it has also become clear that exogenous administration of VEGF is neuroprotective in animal models of central nervous system diseases. In the present study, VEGF was incorporated into a sustained release hydrogel delivery system to examine its potential benefits in a rat model of Huntington's disease (HD). The VEGF-containing hydrogel was stereotaxically injected into the striatum of adult rats. Three days later, quinolinic acid (QA; 225 nmol) was injected into the ipsilateral striatum to produce neuronal loss and behavioral deficits that mimic those observed in HD. Two weeks after surgery, animals were tested for motor function using the placement and cylinder tests. Control animals received either QA alone or QA plus empty hydrogel implants. Behavioral testing confirmed that the QA lesion resulted in significant deficits in the ability of the control animals to use their contralateral forelimb. In contrast, the performance of those animals receiving VEGF was significantly improved relative to controls with only modest motor impairments observed. Stereological counts of NeuN-positive neurons throughout the striatum demonstrated that VEGF implants significantly protected against the loss of striatal neurons induced by QA. These data are the first to demonstrate that VEGF can be used to protect striatal neurons from excitotoxic damage in a rat model of HD.
Emerich
Dwaine F
DF
InCytu, Inc, 701 George Washington Highway, Lincoln, RI, 02865, USA. ED3FJM@aol.com
Mooney
David J
DJ
Storrie
Hannah
H
Babu
Rangasamy Suresh
RS
Kordower
Jeffrey H
JH
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D004195:Disease Models, Animal; D007839:Functional Laterality; D006816:Huntington Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D020100:Hydrogels / Q000008:administration & dosage*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects; D017378:Quinolinic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*
D020100:Hydrogels; D018696:Neuroprotective Agents; D042461:Vascular Endothelial Growth Factor A; D010751:Phosphopyruvate Hydratase; D017378:Quinolinic Acid