title: Extracellular cyclophilin A protects against blast-induced neuronal injury.
abstract: Blast-induced traumatic brain injury (TBI) and subsequent neurobehavioral deficits are major disabilities suffered by the military and civilian population worldwide. Rigorous scientific research is underway to understand the mechanism of blast TBI and thereby develop effective therapies for protection and treatment. By using an in vitro shock tube model of blast TBI with SH-SY5Y human neuroblastoma cells, we have demonstrated that blast exposure leads to neurobiological changes in an overpressure and time dependent manner. Paradoxically, repeated blast exposures resulted in less neuronal injury compared to single blast exposure and suggested a potential neuroprotective mechanism involving released cyclophilin A (CPA). In the present study, we demonstrate accumulation of CPA in the culture medium after repeated blast exposures supporting the notion of extracellular CPA mediated neuroprotection. Post-exposure treatment of the cells with purified recombinant CPA caused significant protection against blast-induced neuronal injury. Furthermore, repeated blast exposure was associated with phosphorylation of the proteins ERK1/2 and Bad suggesting a potential mechanism of neuroprotection by extracellular CPA and may aid in the development of targeted therapies for protection against blast-induced TBI.
authors.affiliation: Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD 20910, USA. peethambaran.arun@amedd.army.mil
authors.forename: Peethambaran
authors.initials: P
authors.lastname: Arun
authors.forename: Rania
authors.initials: R
authors.lastname: Abu-Taleb
authors.forename: Manojkumar
authors.initials: M
authors.lastname: Valiyaveettil
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Long
authors.forename: Madhusoodana P
authors.initials: MP
authors.lastname: Nambiar
mesh_terms: D001753:Blast Injuries / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D021984:Cyclophilin A / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology
chemical_list: D018696:Neuroprotective Agents; D021984:Cyclophilin A