Neuregulin-1 is neuroprotective in a rat model of organophosphate-induced delayed neuronal injury
| Autor: | Yonggang Li, Catherine Ross-Inta, Cecilia R Giulivi, Cuimei Liu, Gregory D. Ford, Teclemichael Tewolde, Byron D. Ford, Donald A. Bruun, Pamela J. Lein |
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| Rok vydání: | 2012 |
| Předmět: |
Atropine
Male Isoflurophate Neuregulin-1 Brain damage Pharmacology Toxicology medicine.disease_cause Neuroprotection Article Rats Sprague-Dawley chemistry.chemical_compound Seizures medicine Animals Protein Isoforms Cholinesterase Neurons biology business.industry Organophosphate Brain Immunohistochemistry Rats Neuroprotective Agents Pyridostigmine chemistry Anesthesia Toxicity biology.protein Cholinesterase Inhibitors medicine.symptom business Oxidative stress Pyridostigmine Bromide medicine.drug |
| Zdroj: | Toxicology and Applied Pharmacology. 262:194-204 |
| ISSN: | 0041-008X |
| Popis: | Current medical countermeasures against organophosphate (OP) nerve agents are effective in reducing mortality, but do not sufficiently protect the CNS from delayed brain damage and persistent neurological symptoms. In this study, we examined the efficacy of neuregulin-1 (NRG-1) in protecting against delayed neuronal cell death following acute intoxication with the OP diisopropylfluorophosphate (DFP). Adult male Sprague Dawley rats were pretreated with pyridostigmine (0.1 mg/kg BW, i.m.) and atropine methylnitrate (20 mg/kg BW, i.m.) prior to DFP (9 mg/kg BW, i.p.) intoxication to increase survival and reduce peripheral signs of cholinergic toxicity but not prevent DFP-induced seizures or delayed neuronal injury. Pretreatment with NRG-1 did not protect against seizures in rats exposed to DFP. However, neuronal injury was significantly reduced in most brain regions by pretreatment with NRG-1 isoforms NRG-EGF (3.2 μg/kg BW, i.a) or NRG-GGF2 (48 μg/kg BW, i.a.) as determined by FluroJade-B labeling in multiple brain regions at 24 h post-DFP injection. NRG-1 also blocked apoptosis and oxidative stress-mediated protein damage in the brains of DFP-intoxicated rats. Administration of NRG-1 at 1 h after DFP injection similarly provided significant neuroprotection against delayed neuronal injury. These findings identify NRG-1 as a promising adjuvant therapy to current medical countermeasures for enhancing neuroprotection against acute OP intoxication. |
| Databáze: | OpenAIRE |
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