title: Effect of methylprednisolone on the axonal impairment accompanying cellular brain oedema induced by water intoxication in rats.
abstract: OBJECTIVE
  Our previous experiments proved that methylprednisolone (MP) can significantly reduce axonal impairment accompanying extracellular oedema induced by the osmotic challenge (load) on the blood-brain barrier (BBB). The aim of the present work was to identify whether MP can affect myelin impairment accompanying intracellular oedema induced by water intoxication.
  
  
  METHODS
  For induction of cellular brain oedema, the standard model of water intoxication was chosen. Animals received distilled water in amount corresponding to 15% of the animal's body weight. The volume was divided into three parts and administered intraperitoneally in 8 hours interval. Axonal changes were recognized as signs of myelin disintegration (oedematous distensions, axonal swelling, vesicles, varicosities) at histological sections stained with Black Gold and classified into four grades of myelin degradation. Hippocampal CA1 and CA3 areas and the dentate gyrus were selected for the study. Methylprednisolone was administered either intraperitoneally or intracarotically. Its effect was studied in two different time intervals: in the acute group (30 minutes after hyperhydration and MP application) and in chronic one (1 week after hyperhydration and MP application).
  
  
  RESULTS
  In both the acute and chronic groups, cellular oedema induced by water intoxication brought about apparent damage of myelin (compared to control animals p<0.0001). Intracarotic injection of MP was not able to influence myelin integrity changes either in the acute or in chronic group. However, intraperitoneal administration of MP increased the level of myelin deterioration in the acute group (p 0.05), but improved myelin changes in the chronic group (p<0.005).
  
  
  CONCLUSIONS
  The effect of MP on axonal impairment during cellular brain oedema induced by water intoxication differs from that during the extracellular osmotic oedema. In the extracellular oedema, cellular metabolism is not significantly affected and myelin changes can be influenced by the neuroprotective effect of MP. The primary cause of cellular oedema is a disorder of cellular metabolism and myelin impairment is one of the structural consequences of such disorder. That is why the myelin changes are not affected by MP administration in a consistent and specific manner.
authors: Institute of Physiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. pokorny@lf1.cuni.cz
authors: Petr
authors: P
authors: Kozler
authors: Jaroslav
authors: J
authors: Pokorny
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009997:Osmotic Pressure / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014869:Water Intoxication / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D005938:Glucocorticoids; D018696:Neuroprotective Agents; D008775:Methylprednisolone