title: Chronic alcoholism-mediated impairment in the medulla oblongata: a mechanism of alcohol-related mortality in traumatic brain injury?
abstract: Alcohol-related traumatic brain injury (TBI) is a common condition in medical and forensic practice, and results in high prehospital mortality. We investigated the mechanism of chronic alcoholism-related mortality by examining the effects of alcohol on the synapses of the medulla oblongata in a rat model of TBI. Seventy adult male Sprague-Dawley rats were randomly assigned to either ethanol (EtOH) group, EtOH-TBI group, or control groups (water group, water-TBI group). To establish chronic alcoholism model, rats in the EtOH group were given EtOH twice daily (4 g/kg for 2 weeks and 6 g/kg for another 2 weeks). The rats also received a minor strike on the occipital tuberosity with an iron pendulum. Histopathologic and ultrastructure changes and the numerical density of the synapses in the medulla oblongata were examined. Expression of postsynaptic density-95 (PSD-95) in the medulla oblongata was measured by ELISA. Compared with rats in the control group, rats in the chronic alcoholism group showed: (1) minor axonal degeneration; (2) a significant decrease in the numerical density of synapses (p < 0.01); and (3) compensatory increase in PSD-95 expression (p < 0.01). Rats in the EtOH-TBI group showed: (1) high mortality (50%, p < 0.01); (2) inhibited respiration before death; (3) severe axonal injury; and (4) decrease in PSD-95 expression (p < 0.05). Chronic alcoholism induces significant synapse loss and axonal impairment in the medulla oblongata and renders the brain more susceptible to TBI. The combined effects of chronic alcoholism and TBI induce significant synapse and axon impairment and result in high mortality.
authors.affiliation: Department of Forensic Medicine, Shantou University Medical College, Xinling Road 22, Shantou, Guangdong, 515031, People's Republic of China.
authors.forename: Xiao-ping
authors.initials: XP
authors.lastname: Lai
authors.forename: Xiao-jun
authors.initials: XJ
authors.lastname: Yu
authors.forename: Hong
authors.initials: H
authors.lastname: Qian
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.forename: Jun-yao
authors.initials: JY
authors.lastname: Lv
authors.forename: Xiao-hu
authors.initials: XH
authors.lastname: Xu
mesh_terms: D000437:Alcoholism / Q000150:complications*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism / Q000401:mortality*; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D000431:Ethanol / Q000633:toxicity*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000431:Ethanol