title: Alpha-linolenic acid is a potent neuroprotective agent against soman-induced neuropathology.
abstract: Nerve agents are deadly threats to military and civilian populations around the world. Nerve agents cause toxicity to peripheral and central sites through the irreversible inhibition of acetylcholinesterase, the enzyme that metabolizes acetylcholine. Excessive acetylcholine accumulation in synapses results in status epilepticus in the central nervous system. Prolonged status epilepticus leads to brain damage, neurological dysfunction and poor outcome. Anticonvulsants are effective but must be given rapidly following exposure. Because these agents cause mass casualties, effective neuroprotective agents are needed to reduce brain damage and improve cognitive outcome. α-Linolenic acid is an omega-3 fatty acid that is found in vegetable products and has no known side effects. α-Linolenic acid is neuroprotective against kainic acid-induced brain damage in vivo, but its neuroprotective efficacy against nerve agents is unknown. α-Linolenic acid also exerts anti-depressant and anti-inflammatory activities and enhances synaptic plasticity in vivo. These properties make this polyunsaturated fatty acid (PUFA) a potential candidate against nerve agent-induced neuropathology. Here we show that α-linolenic acid is neuroprotective against soman-induced neuropathology in either a pretreatment or post-treatment paradigm. We also show that subcutaneous injection of α-linolenic acid shows greater neuroprotective efficacy compared with intravenous injection in a brain region-specific manner.
authors.affiliation: Department of Neurology and Program in Neuroscience, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors.forename: Hongna
authors.initials: H
authors.lastname: Pan
authors.forename: Xian-zhang
authors.initials: XZ
authors.lastname: Hu
authors.forename: David M
authors.initials: DM
authors.lastname: Jacobowitz
authors.forename: Cynthia
authors.initials: C
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: McDonough
authors.forename: Kerry
authors.initials: K
authors.lastname: Van Shura
authors.forename: Megan
authors.initials: M
authors.lastname: Lyman
authors.forename: Ann M
authors.initials: AM
authors.lastname: Marini
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000209:etiology / Q000517:prevention & control; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D024202:Electrophoretic Mobility Shift Assay; D005452:Fluoresceins; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000150:complications / Q000209:etiology* / Q000517:prevention & control*; D009930:Organic Chemicals; D051381:Rats; D017207:Rats, Sprague-Dawley; D012999:Soman / Q000633:toxicity; D017962:alpha-Linolenic Acid / Q000627:therapeutic use*
chemical_list: D002800:Cholinesterase Inhibitors; D005452:Fluoresceins; D016328:NF-kappa B; D018696:Neuroprotective Agents; D009930:Organic Chemicals; C435731:fluoro jade; D017962:alpha-Linolenic Acid; D012999:Soman