Comparison of different osmotic therapies in a mouse model of traumatic brain injury

Pharmacol Rep. 2017 Feb;69(1):176-184. doi: 10.1016/j.pharep.2016.10.007. Epub 2016 Oct 11.

Abstract

Background: Inflammation in the affected region, increased intracranial pressure, consequent oedema and congestion contribute to the negative outcome of traumatic brain injury. Osmotic therapies are recommended for improvement in cognitive and motor functions. Aim of the present study was to evaluate the effect of osmotic therapies in a mice model of traumatic brain injury.

Methods: Experimental closed head injury was performed in adult Swiss albino mice by the weight-drop method. Different group of animals were treated with normal saline (G1), mannitol (G2), mannitol+glycerin (G3) and Neurotol (G4). Neurological Severity Score (NSS) was recorded at different time-points upto a period of six days. Effect of treatments on cerebral oedema, learning and memory function, motor function and co-ordination were evaluated by gravimetry, Morris water maze and beam walk test respectively. Histopathology was performed to evaluate the treatment effects on microscopic complications arising from primary closed head injury (CHI).

Results: All the treatments showed a marked improvement in the evaluated parameters as compared with the vehicle control group. It was evident that G3 and G4 had a distinct advantage over mannitol therapy. Based on the NSS score, Neurotol proved to be comparatively safe and more efficacious than either mannitol or a combination of mannitol+glycerol. The effect of Neurotol could have been enhanced by the presence of VRP011 (a Mg+2 salt).

Conclusions: Neurotol is safe and exhibits better efficacy as compared with other treatments for the management of traumatic brain injury.

Keywords: Glycerol; Mannitol; Osmotic therapy; Trauma.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Brain Injuries, Traumatic / drug therapy*
  • Brain Injuries, Traumatic / pathology
  • Brain Injuries, Traumatic / physiopathology
  • Carbamazepine / pharmacology
  • Carbamazepine / therapeutic use*
  • Disease Models, Animal*
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Mice
  • Osmosis / drug effects*
  • Osmosis / physiology

Substances

  • Carbamazepine