title: The effects of N-acetyl-cysteine and acetyl-L-carnitine on neural survival, neuroinflammation and regeneration following spinal cord injury.
abstract: Traumatic spinal cord injury induces a long-standing inflammatory response in the spinal cord tissue, leading to a progressive apoptotic death of spinal cord neurons and glial cells. We have recently demonstrated that immediate treatment with the antioxidants N-acetyl-cysteine (NAC) and acetyl-l-carnitine (ALC) attenuates neuroinflammation, induces axonal sprouting, and reduces the death of motoneurons in the vicinity of the trauma zone 4weeks after initial trauma. The objective of the current study was to investigate the effects of long-term antioxidant treatment on the survival of descending rubrospinal neurons after spinal cord injury in rats. It also examines the short- and long-term effects of treatment on apoptosis, inflammation, and regeneration in the spinal cord trauma zone. Spinal cord hemisection performed at the level C3 induced a significant loss of rubrospinal neurons 8 weeks after injury. At 2 weeks, an increase in the expression of the apoptosis-associated markers BCL-2-associated X protein (BAX) and caspase 3, as well as the microglial cell markers OX42 and ectodermal dysplasia 1 (ED1), was seen in the trauma zone. After 8 weeks, an increase in immunostaining for OX42 and the serotonin marker 5HT was detected in the same area. Antioxidant therapy reduced the loss of rubrospinal neurons by approximately 50%. Treatment also decreased the expression of BAX, caspase 3, OX42 and ED1 after 2 weeks. After 8 weeks, treatment decreased immunoreactivity for OX42, whereas it was increased for 5HT. In conclusion, this study provides further insight in the effects of treatment with NAC and ALC on descending pathways, as well as short- and long-term effects on the spinal cord trauma zone.
authors.affiliation: Department of Integrative Medical Biology, Section of Anatomy, Umeå University, SE-901 87 Umeå, Sweden; Department of Surgical and Perioperative Science, Section of Hand and Plastic Surgery, Umeå University, SE-901 87 Umeå, Sweden. Electronic address: amar.karalija@anatomy.umu.se.
authors.forename: A
authors.initials: A
authors.lastname: Karalija
authors.affiliation: Department of Integrative Medical Biology, Section of Anatomy, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: L N
authors.initials: LN
authors.lastname: Novikova
authors.affiliation: Department of Integrative Medical Biology, Section of Anatomy, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: P J
authors.initials: PJ
authors.lastname: Kingham
authors.affiliation: Department of Integrative Medical Biology, Section of Anatomy, Umeå University, SE-901 87 Umeå, Sweden; Department of Surgical and Perioperative Science, Section of Hand and Plastic Surgery, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Wiberg
authors.affiliation: Department of Integrative Medical Biology, Section of Anatomy, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: L N
authors.initials: LN
authors.lastname: Novikov
mesh_terms: D000108:Acetylcarnitine / Q000494:pharmacology*; D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001369:Axons / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002574:Cervical Vertebrae; D004195:Disease Models, Animal; D005260:Female; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D000108:Acetylcarnitine; D000111:Acetylcysteine
keywords: adult rats; antioxidants; apoptosis; motoneurons; spinal cord