title: Therapeutic effects of intrathecal versus intravenous monosialoganglioside against bupivacaine-induced spinal neurotoxicity in rats.
abstract: BACKGROUND
  Bupivacaine causes neuronal and axonal degeneration, leading to cauda equina syndrome or permanent nerve damage. Our previous studies have shown that intrathecal or intravenous gangliosides monosialogangliosides (GM-1s) have therapeutic effects against bupivacaine-induced neurotoxicity, but we do not know what are the differences between the two methods.
  
  
  RESULTS
  Bupivacaine-induced neurotoxicity was induced in rats by three times injection of 5% bupivacaine (0.24μl/g) to the L3 spinal cord. We observed by H&E staining that bupivacaine caused obvious neuronal injuries in the spinal cord, such as edema, vacuolation of myelin sheaths, and neuronal degeneration. Electron microscopy revealed similar pathohistological changes. Neural functions, evaluated by tail-flicking test and locomotor scaling, were also impaired. Treatment with GM-1s (30mg/kg) repaired the neural lesions and gradually improved the neural functions. By days 14 and 28 post GM-1s, the pathohistological changes in the posterior root and posterior column had significantly recovered but not completely. Compared with intravenous routes, intrathecal application of GM-1s demonstrated faster and greater efficacies in regeneration of neural damages and in improvement of neural dysfunctions. Caspase-3, a marker of cellular apoptosis, was shown by immunohistochemistry to be suppressed in protein transcription by GM-1s application and intrathecal GM-1s had potentiated a greater reduction in caspase-3 protein than intravenous GM-1s.
  
  
  CONCLUSIONS
  Treatment with GM-1s in intrathecal routes more effectively reverses bupivacaine-induced neural injuries and improves the neural dysfunctions than intravenous routes. This may be partly attributed to that GM-1 inhibits the expression of cellular apoptosis factor caspase-3 protein.
authors: Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, 22 Shuangyong Road, Nanning City 530021, Guangxi Province, People's Republic China.
authors: Jiemei
authors: J
authors: Ji
authors: Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, 22 Shuangyong Road, Nanning City 530021, Guangxi Province, People's Republic China.
authors: Xiurong
authors: X
authors: Yan
authors: Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, People's Republic China.
authors: Zuyun
authors: Z
authors: Li
authors: Department of Pharmacology, The Guangxi Medical University, Nanning 530021, People's Republic China.
authors: Zefeng
authors: Z
authors: Lai
authors: Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, 22 Shuangyong Road, Nanning City 530021, Guangxi Province, People's Republic China. Electronic address: liu2774@hotmail.com.
authors: Jingchen
authors: J
authors: Liu
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000648:ultrastructure; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002045:Bupivacaine / Q000009:adverse effects*; D053148:Caspase 3 / Q000378:metabolism; D005732:Gangliosides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006358:Hot Temperature; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009186:Myelin Sheath / Q000187:drug effects / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology
chemical_list: D005732:Gangliosides; C025447:sialogangliosides; D053148:Caspase 3; D002045:Bupivacaine
keywords: Apoptosis; Bupivacaine; Ganglioside GM-1; Neurotoxicity