TY - JOUR
T1 - Lecithinized superoxide dismutase (PC-SOD) improved spinal cord injury-induced motor dysfunction through suppression of oxidative stress and enhancement of neurotrophic factor production
AU - Takenaga, Mitsuko
AU - Ohta, Yuki
AU - Tokura, Yukie
AU - Hamaguchi, Akemi
AU - Nakamura, Masaya
AU - Okano, Hideyuki
AU - Igarashi, Rie
N1 - Funding Information:
This study was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology (Development of Stem Cell Therapy for Spinal Cord Injury and Neural Stem Cell Bank) in Japan.
PY - 2006/1/10
Y1 - 2006/1/10
N2 - PC-SOD (lecithinized superoxide dismutase) is a derivative of human Cu, Zn-SOD conjugated with 4 molecules of lecithin, yet having the enzyme activity of scavenging superoxide anion (O2-). Intravenous administration of PC-SOD promoted the recovery from spinal cord injury (SCI)-induced motor dysfunction in a dose-dependent manner in rat model, when evaluated by BBB (Basso Beattie Bresnahan) score. Even when given at 24 h after SCI, PC-SOD (1 mg/kg) significantly improved motor dysfunction. Distribution study demonstrated that PC-SOD gradually accumulated to the injured site. Enzyme-linked immunoassay revealed that PC-SOD prevented quantitative loss of neurons, astrocytes, and oligodendrocytes. PC-SOD inhibited SCI-induced oxidative stress, such as the decrease of free sulfhydryl residue, acetylcholine esterase activity, and the increase of lipid peroxidation. PC-SOD increased the production of neuroprotective factors. HIF-1α gene expression increased following SCI, and PC-SOD further increased it. In conclusion, PC-SOD gradually accumulated and retained at the damaged site to scavenge excessive O 2-, and suppressed neuronal death through reducing oxidative stress, increasing neuroprotective factor production and HIF-1α gene expression.
AB - PC-SOD (lecithinized superoxide dismutase) is a derivative of human Cu, Zn-SOD conjugated with 4 molecules of lecithin, yet having the enzyme activity of scavenging superoxide anion (O2-). Intravenous administration of PC-SOD promoted the recovery from spinal cord injury (SCI)-induced motor dysfunction in a dose-dependent manner in rat model, when evaluated by BBB (Basso Beattie Bresnahan) score. Even when given at 24 h after SCI, PC-SOD (1 mg/kg) significantly improved motor dysfunction. Distribution study demonstrated that PC-SOD gradually accumulated to the injured site. Enzyme-linked immunoassay revealed that PC-SOD prevented quantitative loss of neurons, astrocytes, and oligodendrocytes. PC-SOD inhibited SCI-induced oxidative stress, such as the decrease of free sulfhydryl residue, acetylcholine esterase activity, and the increase of lipid peroxidation. PC-SOD increased the production of neuroprotective factors. HIF-1α gene expression increased following SCI, and PC-SOD further increased it. In conclusion, PC-SOD gradually accumulated and retained at the damaged site to scavenge excessive O 2-, and suppressed neuronal death through reducing oxidative stress, increasing neuroprotective factor production and HIF-1α gene expression.
KW - BBB (Basso Beattie Bresnahan) score
KW - Lecithinized superoxide dismutase (PC-SOD)
KW - Spinal cord injury (SCI)
KW - Unmodified SOD (U-SOD)
UR - http://www.scopus.com/inward/record.url?scp=29244484263&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=29244484263&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2005.10.022
DO - 10.1016/j.jconrel.2005.10.022
M3 - Article
C2 - 16332351
AN - SCOPUS:29244484263
SN - 0168-3659
VL - 110
SP - 283
EP - 289
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -