Arachidonyl trifluoromethyl ketone is neuroprotective after spinal cord injury.
In spinal cord injury (SCI), neuronal and oligodendroglial loss occurs as a result of the initial trauma and the secondary damage that is triggered by excitotoxicity, free radicals, and inflammation. There is evidence that SCI ellicits increased cytosolic phospholipase A(2) (cPLA(2)) activity. The cleavage of phospholipids by cPLA(2) leads to release of fatty acids, and in particular arachidonic acid (AA), the metabolites of which have been associated with increased inflammation and oxidative stress. The aim of our study was to investigate whether the inhibition of cPLA(2) following SCI leads to tissue protection and an improved functional outcome. Adult rats received compression SCI and 30 min after injury they were treated intravenously with either saline or the cPLA(2) inhibitor arachidonyl trifluoromethyl ketone (AACOCF3) (7.13 mg/kg). The animals were sacrificed at 7 days post-injury and the lesioned tissue was labeled using markers for neurons, oligodendrocytes, and macrophages/activated microglia. We also assessed locomotor recovery using the Basso-Beattie-Bresnahan (BBB) score. The number of surviving neurons and oligodendrocytes was significantly increased in animals treated with the cPLA(2) inhibitor compared to saline controls. The behavioral analysis mirrored the neuroprotective effects and showed that the inhibitor-treated group had better locomotor recovery compared to saline controls. Our results show that AACOCF3 has neuroprotective potential, and support the idea that cPLA(2) is critically involved in acute spinal injury.
Neuroscience Centre, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London, United Kingdom.
Wenlong
W
Huang
Amar
A
Bhavsar
Rachael E
RE
Ward
Jodie C E
JC
Hall
John V
JV
Priestley
Adina T
AT
Michael-Titus
D000704:Analysis of Variance; D000818:Animals; D001095:Arachidonic Acids / Q000627:therapeutic use*; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects*; D007150:Immunohistochemistry; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013117:Spinal Cord Compression / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D001095:Arachidonic Acids; D018696:Neuroprotective Agents; C081565:arachidonyltrifluoromethane