AR-A014418 as a glycogen synthase kinase-3 inhibitor: Anti-apoptotic and therapeutic potential in experimental spinal cord injury
Neurocirugia, cilt.24, sa.1, ss.22-32, 2013 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 24 Sayı: 1
- Basım Tarihi: 2013
- Doi Numarası: 10.1016/j.neucir.2011.12.006
- Dergi Adı: Neurocirugia
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.22-32
- Anahtar Kelimeler: Apoptosis, AR-A014418, GSK-3beta, Spinal cord injury, TGF-beta
- Maltepe Üniversitesi Adresli: Evet
Özet
Objectives: We aimed to investigate the effects of AR-A014418, a strong inhibitor specific to GSK-3beta, on neuronal apoptosis and neuroprotection in the traumatic SCI model. Materials and methods: In this study, three groups were generated from 36 Wistar rats; (1) control, (2) spinal cord trauma group created by clip compression technique after laminectomy, and (3) AR-A014418 (4 mg/kg, i.p., DMSO) treatment group after laminectomy and spinal cord trauma. The TUNEL assay for apoptosis detection, immunohistochemical staining for bax and TGF-beta were applied in spinal cord tissues. For light microscopic examination, necrotic, and apoptotic cells were counted, and PMNL counting was applied to detect inflammation. Functional recovery was tested by field locomotor test in the 3rd and 7th days following surgery. Results: In the trauma group, diffuse hemorrhage, cavitation, necrosis and edematous regions, degeneration in motor neurons and leukocyte infiltration were observed in gray matter. In the AR-A014418-treated groups, healthy cells were observed in more places compared to the trauma groups, however, cavitation, hemorrhagic, and edematous areas were seen in gray matter. In the AR-A014418-treatment groups, the number of apoptotic cells in the 3rd and 7th days (respectively; p < 0.05, p < 0.01), were significantly decreased compared to the trauma groups, as were the levels of bax (p < 0.01) and TGF-beta 1 immunoreactivity. Results of the locomotor test were significantly increased in the treatment group (p < 0.001) as compared to the trauma group. © 2012 Sociedad Española de Neurocirugía.