Neuroprotective effects of bone morphogenetic protein 7 (BMP7) treatment after spinal cord injury.
Bone morphogenetic protein 7 (BMP7) has been shown to ameliorate reduced dendritic growth induced by glutamate excitotoxicity in neuronal tissue cultures and/or provide an enhancement of functional recovery in central nervous system (CNS) injury. BMP7 expression is modulated by spinal cord injury (SCI), but the molecular mechanisms involved in neuroprotection have not been clearly defined. Here, we show that BMP7 treatment of rats subjected to mild cervical SCI significantly increased the pro-survival mitogen-activated protein kinase-38 (MAPK-38) pathway and levels of N-methyl-D-aspartate receptor 1 (NMDAR-1) resulting in a significant increase in neuronal sparing in the ventral horn of the spinal cord. Moreover, BMP7 was neuroprotective against glutamate-mediated excitotoxicity in cultured cortical neurons. These studies show that BMP7 administration may be used as a therapeutic strategy to reduce the damaging excitotoxic effects following SCI.
de Rivero Vaccari
Juan Pablo
JP
Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, United States.
Marcillo
Alex
A
Nonner
Doris
D
Dietrich
W Dalton
WD
Keane
Robert W
RW
D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000008:administration & dosage*; D002470:Cell Survival / Q000187:drug effects; D002574:Cervical Vertebrae / Q000293:injuries; D004305:Dose-Response Relationship, Drug; D005260:Female; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage; D051381:Rats; D011916:Rats, Inbred F344; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism*; D016896:Treatment Outcome
D055419:Bone Morphogenetic Protein 7; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; C525821:Bmp7 protein, rat