title: Contusive spinal cord injury up regulates mu-opioid receptor (mor) gene expression in the brain and down regulates its expression in the spinal cord: possible implications in spinal cord injury research.
abstract: Traumatic spinal cord injury (SCI) is one of the dreaded neurological conditions and finding a cure for it has been a hot area of research. Naloxone - a mu-opiate receptor (mor) antagonist was considered for SCI treatment based on its positive effects under shock conditions. In contrary to animal studies based reports about the potential benefits of naloxone in treating SCI, a large scale clinical trial [National Acute Spinal Cord Injury Study II (NASCIS II)] conducted in USA failed to witness any effectiveness. The inconsistency noticed was intriguing. Therefore, the objective of the present study was to re-examine the role of naloxone in treating SCI using a highly standardised Multicenter Animal Spinal Cord Injury Study (MASCIS) animal model of contusive SCI. Results indicated that naloxone produced negligible and insignificant neuroprotection. In an attempt to understand the cause for the failure, it was found that mu-opioid receptor (mor) gene expression was upregulated in the brain but was down regulated in the spinal cord after contusive SCI. Given that the beneficial effects of naloxone are through its action on the mor, the results indicate that unlike the brain, spinal cord might not be bracing to utilise the opiate system in the repair process. This could possibly explain the failure of naloxone treatment in NASCIS II. To conclude, opiate antagonists like naloxone may be neuroprotective for treating traumatic brain injuries, but not for traumatic/contusive spinal cord injuries.
authors.forename: Felicia Mary
authors.initials: FM
authors.lastname: Michael
authors.forename: Alok Nath
authors.initials: AN
authors.lastname: Mohapatra
authors.forename: Lavanya
authors.initials: L
authors.lastname: Venkitasamy
authors.forename: Kirubhanand
authors.initials: K
authors.lastname: Chandrasekar
authors.forename: Tenzin
authors.initials: T
authors.lastname: Seldon
authors.forename: Sankar
authors.initials: S
authors.lastname: Venkatachalam
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001973:Bromodeoxyuridine / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000008:administration & dosage*; D009292:Narcotic Antagonists / Q000008:administration & dosage*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D034961:Antigens, Nuclear; D009292:Narcotic Antagonists; D009419:Nerve Tissue Proteins; C546339:Rbfox3 protein, rat; D017450:Receptors, Opioid, mu; D009270:Naloxone; D001973:Bromodeoxyuridine
keywords: Injury response in brain and spinal cord; Naloxone,; Neurogenesis,; Neuroprotection,