Gene therapy effectiveness differs for neuronal survival and behavioral performance.
If neuronal gene therapy is to be clinically useful, it is necessary to demonstrate neuroprotection when the gene is introduced after insult. We now report equivalent neuronal protection if calbindin D(28K) gene transfer via herpes simplex virus amplicon vector occurs immediately, 30 min, or 1 h after an excitotoxic insult, but not after a 4 h delay. Behavioral performance was evaluated for immediate and 1 h delay groups using a hippocampal-dependent task. Despite equivalent magnitude and pattern of sparing of neurons with the immediate and 1 h delay approaches, the delay animals took a significantly longer time after insult to return to normal performance.
Phillips
R G
RG
Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020 USA.
Monje
M L
ML
Giuli
L C
LC
Meier
T J
TJ
Yenari
M A
MA
Kunis
D
D
Sapolsky
R M
RM
D000818:Animals; D001522:Behavior, Animal; D001930:Brain Injuries / Q000473:pathology / Q000523:psychology / Q000628:therapy*; D064026:Calbindins; D002470:Cell Survival / Q000235:genetics; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006624:Hippocampus / Q000473:pathology; D007608:Kainic Acid; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000473:pathology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000235:genetics* / Q000378:metabolism; D018139:Simplexvirus / Q000235:genetics; D013997:Time Factors
D064026:Calbindins; D009419:Nerve Tissue Proteins; D064030:S100 Calcium Binding Protein G; D007608:Kainic Acid