title: Magnesium Lithospermate B Implicates 3'-5'-Cyclic Adenosine Monophosphate/Protein Kinase A Pathway and N-Methyl-d-Aspartate Receptors in an Experimental Traumatic Brain Injury.
abstract: OBJECTIVE
  Decreased 3'-5'-cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and increased N-methyl-d-aspartate (NMDA) related apoptosis were observed in traumatic brain injury (TBI). It is of interest to examine the effect of magnesium lithospermate B (MLB) on cAMP/PKA pathway and NMDAR in TBI.
  
  
  METHODS
  A rodent weight-drop TBI model was used. Administration of MLB was initiated 1 week before (precondition) and 24 hours later (reversal). Cortical homogenates were harvested to measure cAMP (enzyme-linked immunosorbent assay), soluble guanylyl cyclases, PKA and NMDA receptor-2β (Western blot). In addition, cAMP kinase antagonist and H-89 dihydrochloride hydrate were used to test MLB's effect on the cytoplasm cAMP/PKA pathway after TBI.
  
  
  RESULTS
  Morphologically, vacuolated neuron and activated microglia were observed in the TBI groups but absent in the MLB preconditioning and healthy controls. Induced cAMP, soluble guanylyl cyclase α1, and PKA were observed in the MLB groups, when compared with the TBI group (P < 0.01) Administration of H-89 dihydrochloride hydrate reversed the effect of MLB on cortical PKA and NMDA-2β expression after TBI.
  
  
  CONCLUSIONS
  This study showed that MLB exerted an antioxidant effect on the enhancement of cytoplasm cAMP and PKA. This compound also decreased NMDA-2β levels, which may correspond to its neuroprotective effects. This finding lends credence to the presumption that MLB modulates the NMDA-2β neurotoxicity through a cAMP-dependent mechanism in the pathogenesis of TBI.
authors.affiliation: Department of Surgery, Faculty of Medicine, School of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Surgery, Kaohsiung Municipal Ta Tung Hospital, Kaohsiung, Taiwan. Electronic address: changchihzen2002@yahoo.com.tw.
authors.forename: Chih-Zen
authors.initials: CZ
authors.lastname: Chang
authors.affiliation: Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Shu-Chuan
authors.initials: SC
authors.lastname: Wu
authors.affiliation: Department of Surgery, Faculty of Medicine, School of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Aij-Lie
authors.initials: AL
authors.lastname: Kwan
authors.affiliation: Department of Surgery, Faculty of Medicine, School of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Chih-Lung
authors.initials: CL
authors.lastname: Lin
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001929:Brain Edema / Q000473:pathology; D001930:Brain Injuries / Q000473:pathology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009422:Nervous System Diseases / Q000209:etiology / Q000523:psychology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D000071756:Soluble Guanylyl Cyclase; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D016194:Receptors, N-Methyl-D-Aspartate; D013449:Sulfonamides; C061091:lithospermate B; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
keywords: 3′-5′-Cyclic adenosine monophosphate; H-89 Dihydrochloride hydrate; Magnesium lithospermate B; N-Methyl-d-aspartate; Traumatic brain injury