title: The influence of benzamil hydrochloride on the evolution of hyponatremic brain edema as assessed by in vivo MRI study in rats.
abstract: OBJECTIVE
  The present study was undertaken to reveal the influence of intracerebroventricular (ICV) benzamil on the dynamics of brain water accumulation in hyponatremic rats. Parameters of brain water homeostasis were continuously monitored, using in vivo magnetic resonance imaging (MRI) methods. The results were compared with those obtained in a previous study by tissue desiccation.
  
  
  METHODS
  A 3-T MRI instrument was applied to perform serial diffusion-weighted imaging to measure the apparent diffusion coefficient (ADC) and MR spectroscopy to determine water signal. A decrease of ADC is thought to represent an increase of intracellular water, whereas water signal is used to quantify brain water content. Five groups of male Wistar rats were studied as follows: normonatremic, native animals (group NN, n = 7), hyponatremic animals (group HN, n = 8), hyponatremic animals treated with ICV benzamil (group HNB, n = 8), hyponatremic animals treated with ICV saline (group HNS, n = 5) and normonatremic animals treated with ICV benzamil (group NNB, n = 5). Hyponatremia was induced by intraperitoneal administration of 140 mmol/l dextrose solution in a dose of 20% of body weight. Benzamil hydrochloride (4 μg) was injected ICV to the treated animals.
  
  
  RESULTS
  During the course of hyponatemia, ADC declined steadily from the baseline (100%) to reach a minimum of 92.32 ± 3.20% at 90 min (p < 0.0005). This process was associated with an increase in water signal to a maximum of 5.95 ± 2.62% at 100 min (p < 0.0005). After pretreatment with benzamil, no consistent changes occurred either in ADC or in water signal.
  
  
  CONCLUSIONS
  These findings suggest that sodium channel blockade with ICV benzamil has an immediate protective effect against the development of hyponatremic brain edema. Sodium channels, therefore, appear to be intimately involved in the initiation and progression of brain water accumulation in severe hyponatremia.
authors: Department of Neurosurgery, Faculty of Medicine, University of Pécs, Rét Street 2, 7623, Pécs, Hungary. roy.steier@gmail.com
authors: Roy
authors: R
authors: Steier
authors: Mihály
authors: M
authors: Aradi
authors: József
authors: J
authors: Pál
authors: Péter
authors: P
authors: Bukovics
authors: Gábor
authors: G
authors: Perlaki
authors: Gergely
authors: G
authors: Orsi
authors: József
authors: J
authors: Janszky
authors: Attila
authors: A
authors: Schwarcz
authors: Endre
authors: E
authors: Sulyok
authors: Tamás
authors: T
authors: Dóczi
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004195:Disease Models, Animal; D018450:Disease Progression; D007010:Hyponatremia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D015222:Sodium Channels / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D026941:Sodium Channel Blockers; D015222:Sodium Channels; C013407:benzamil; D000584:Amiloride