PMID- 20190624 OWN - NLM STAT- MEDLINE DCOM- 20100525 LR - 20121115 IS - 1528-1159 (Electronic) IS - 0362-2436 (Linking) VI - 35 IP - 5 DP - 2010 Mar 1 TI - Targeted retrograde gene delivery of brain-derived neurotrophic factor suppresses apoptosis of neurons and oligodendroglia after spinal cord injury in rats. PG - 497-504 LID - 10.1097/BRS.0b013e3181b8e89b [doi] AB - STUDY DESIGN: Histologic and immunohistochemical studies after targeted retrograde adenovirus (AdV)-mediated brain-derived neurotrophic factor (BDNF) gene delivery via intramuscular injection in rats with injured spinal cord. OBJECTIVE: To investigate the neuroprotective effect of targeted retrograde AdV-BDNF gene transfection in the traumatically injured spinal cord in terms of prevention of apoptosis of neurons and oligodendrocytes. SUMMARY OF BACKGROUND DATA: Several studies investigated the neuroprotective effects of neurotrophins including BDNF on spinal cord injury, with respect to prevention of neural cell apoptosis in injured spinal cord. However, no report has described the potential effect of targeted retrograde neurotrophic factor gene delivery in injured spinal cord on prevention of neural cell apoptosis. METHODS: AdV-BDNF or AdV-LacZ was used for retrograde delivery via bilateral sternomastoid muscles to the spinal accessory motoneurons immediately after spinal cord injury in rats. Localization of beta-galactosidase expression produced by LacZ gene or AdV-BDNF gene transfection was examined by immunofluorescence staining and double staining of cell markers (NeuN, RIP, GFAP, OX-42, and NG2) in the injured spinal cord. TUNEL-positive cells were counted and immunoreactivity to active caspase-3 and NG2 was examined after gene injection. RESULTS: Retrograde delivery of LacZ marker gene was identified in cervical spinal neurons and glial cells including oligodendrocytes in the white matter.AdV-BDNF transfection resulted in a significant decrease in the number of TUNEL-positive apoptotic cells by downregulating the caspase apoptotic pathway, with significant promotion of NG2 expression in injured spinal cord, compared with AdV-LacZ injection. CONCLUSION: Our results suggest that targeted retrograde BDNF gene delivery suppresses apoptosis of neurons and oligodendrocytes in the injured rat spinal cord. FAU - Nakajima, Hideaki AU - Nakajima H AD - Department of Orthopaedics and Rehabilitation Medicine, The University of Fukui, Fukui, Japan. FAU - Uchida, Kenzo AU - Uchida K FAU - Yayama, Takafumi AU - Yayama T FAU - Kobayashi, Shigeru AU - Kobayashi S FAU - Guerrero, Alexander Rodriguez AU - Guerrero AR FAU - Furukawa, Shoei AU - Furukawa S FAU - Baba, Hisatoshi AU - Baba H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Spine (Phila Pa 1976) JT - Spine JID - 7610646 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Adenoviridae/genetics MH - Animals MH - Apoptosis/*genetics MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/*genetics/metabolism MH - Cervical Vertebrae MH - Genetic Therapy MH - Genetic Vectors/genetics MH - Immunohistochemistry MH - In Situ Nick-End Labeling MH - Male MH - Neurons/*metabolism/pathology MH - Oligodendroglia/*metabolism/pathology MH - Rats MH - Rats, Sprague-Dawley MH - Spinal Cord Injuries/*genetics/pathology/*therapy MH - Statistics, Nonparametric EDAT- 2010/03/02 06:00 MHDA- 2010/05/26 06:00 CRDT- 2010/03/02 06:00 PHST- 2010/03/02 06:00 [entrez] PHST- 2010/03/02 06:00 [pubmed] PHST- 2010/05/26 06:00 [medline] AID - 00007632-201003010-00006 [pii] AID - 10.1097/BRS.0b013e3181b8e89b [doi] PST - ppublish SO - Spine (Phila Pa 1976). 2010 Mar 1;35(5):497-504. doi: 10.1097/BRS.0b013e3181b8e89b.