Effects of Taxol on Regeneration in a Rat Sciatic Nerve Transection Model.
Recent studies describe taxol as a candidate treatment for promoting central nerve regeneration. However, taxol has serious side effects including peripheral neurotoxicity, and little information is known about the effect of taxol on peripheral nerve regeneration. We investigated the effects of taxol on regeneration in a rat sciatic nerve transection model. Rats were divided into four groups (n = 10): normal saline (i.p.) as the control, Cremophor EL vehicle, and 2 or 6 mg/kg of taxol in the Cremophor EL solution (four times in day-2, 4, 6, and 8), respectively. We evaluated neuronal electrophysiology, animal behaviour, neuronal connectivity, macrophage infiltration, location and expression levels of calcitonin gene-related peptide (CGRP), and expression levels of both nerve growth factors and immunoregulatory factors. In the high-dose taxol group (6 mg/kg), neuronal electrophysiological function was significantly impaired. Licking latencies were significantly changed while motor coordination was unaffected. Neuronal connectivity, macrophage density, and expression levels of CGRP was dramatically reduced. Expression levels of nerve growth factors and immunoregulatory factors was also reduced, while it was increased in the low-dose taxol group (2 mg/kg). These results indicate that taxol can modulate local inflammatory conditions, impair nerve regeneration, and impede recovery of a severe peripheral nerve injury.
Department of Obstetrics and Gynaecology, Taichung Veterans General Hospital, Taichung, Taiwan.|School of Medicine, Lab of Biomaterials, Graduate Institute of Basic Medical Science, Graduate Institute of Biomedical Sciences, Graduate Institute of Integrated Medicine, Department of Biological Science and Technology, Research Center for Chinese Medicine &Acupuncture, China Medical University, Taichung, Taiwan.
Shih-Tien
ST
Hsu
School of Medicine, Lab of Biomaterials, Graduate Institute of Basic Medical Science, Graduate Institute of Biomedical Sciences, Graduate Institute of Integrated Medicine, Department of Biological Science and Technology, Research Center for Chinese Medicine &Acupuncture, China Medical University, Taichung, Taiwan.|Biomaterials Translational Research Center, China Medical University Hospital, Taichung, Taiwan.|Department of Bioinformatics and Medical Engineering, Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan.
Chun-Hsu
CH
Yao
School of Medicine, Lab of Biomaterials, Graduate Institute of Basic Medical Science, Graduate Institute of Biomedical Sciences, Graduate Institute of Integrated Medicine, Department of Biological Science and Technology, Research Center for Chinese Medicine &Acupuncture, China Medical University, Taichung, Taiwan.
Yuan-Man
YM
Hsu
Department of Fiber and Composite Materials, Feng Chia University, Taichung, Taiwan.
Jia-Horng
JH
Lin
School of Medicine, Lab of Biomaterials, Graduate Institute of Basic Medical Science, Graduate Institute of Biomedical Sciences, Graduate Institute of Integrated Medicine, Department of Biological Science and Technology, Research Center for Chinese Medicine &Acupuncture, China Medical University, Taichung, Taiwan.|Department of Bioinformatics and Medical Engineering, Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan.
Yung-Hsiang
YH
Chen
School of Medicine, Lab of Biomaterials, Graduate Institute of Basic Medical Science, Graduate Institute of Biomedical Sciences, Graduate Institute of Integrated Medicine, Department of Biological Science and Technology, Research Center for Chinese Medicine &Acupuncture, China Medical University, Taichung, Taiwan.|Biomaterials Translational Research Center, China Medical University Hospital, Taichung, Taiwan.|Department of Bioinformatics and Medical Engineering, Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan.
Yueh-Sheng
YS
Chen
D059331:Adrenergic Neurons / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D055724:Electrophysiological Phenomena; D005786:Gene Expression Regulation / Q000187:drug effects; D006358:Hot Temperature; D006930:Hyperalgesia / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects*; D017239:Paclitaxel / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology*; D012826:Silicone Elastomers; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013266:Stilbamidines / Q000737:chemistry
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D012333:RNA, Messenger; D012826:Silicone Elastomers; D013266:Stilbamidines; D015740:Calcitonin Gene-Related Peptide; D017239:Paclitaxel