Gene and stem cell therapy in ischemic stroke.
Possible strategies for treating ischemic stroke include neuroprotection (preventing injured neurons from undergoing apoptosis in the acute phase of cerebral ischemia) and stem cell therapy (the repair of disrupted neuronal networks with newly born neurons in the chronic phase of cerebral ischemia). First, we estimated the neuroprotective effect of glial cell line-derived neurotrophic factor (GDNF) by administration of GFNF protein. GDNF protein showed a direct protective effect against ischemic brain damage. Pretreatment of animals with adenoviral vector containing GDNF gene (Ad-GDNF) 24 h before the subsequent transient middle cerebral artery occlusion (MCAO) effectively reduced infarcted volume. Secondly, we studied the neuroprotective effect of a calcium channel blocker, azelnidipine, or a by-product of heme degradation, biliverdin. Both azelnidipine and biliverdin had a neuroprotective effect in the ischemic brain through their antioxidative property. Lastly, we developed a restorative stroke therapy with a bioaffinitive scaffold, which is able to provide an appropriate platform for newly born neurons. In the future, we will combine these strategies to develop more effective therapies for treatment of strokes.
Yamashita
Toru
T
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Deguchi
Kentaro
K
Nagotani
Shoko
S
Kamiya
Tatsushi
T
Abe
Koji
K
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D001664:Biliverdine / Q000627:therapeutic use; D002545:Brain Ischemia / Q000188:drug therapy* / Q000628:therapy*; D004095:Dihydropyridines / Q000627:therapeutic use; D004195:Disease Models, Animal; D015316:Genetic Therapy; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D018696:Neuroprotective Agents / Q000627:therapeutic use; D033581:Stem Cell Transplantation / Q000379:methods*
D000975:Antioxidants; D004095:Dihydropyridines; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D001383:Azetidinecarboxylic Acid; D001664:Biliverdine; C061679:azelnidipine