Resuscitation from experimental traumatic brain injury by agmatine therapy.

Both nitric oxide and glutamate contribute to ischaemic brain injury. Agmatine inhibits all isoforms of nitric oxide synthase and blocks N-methyl-d-aspartate receptors. In this study, we gave agmatine intraperitoneally and assessed its effect on fluid percussion brain injury in rats. Anaesthetised rats, immediately after the onset of fluid percussion traumatic brain injury (TBI), were divided into two major groups and given the vehicle solution (1mL/kg) or agmatine (50mg/kg) intraperitoneally. Mean arterial pressure, intracranial pressure, cerebral perfusion pressure, and levels of glutamate, nitric oxide, lactate/pyruvate ratio, and glycerol in hippocampus were monitored continuously within 120min after TBI. The weight loss was determined by the difference between the first and third day of body weight after TBI. The maximal grip angle in an inclined plane was measured to determine motor performance whereas the percent of maximal possible effect was used to measure blockade of proprioception. The triphenyltetrazolium chloride staining procedures were used for cerebral infarction assay. Compared to those of the sham-operated controls, the animals with TBI had higher values of extracellular levels of glutamate, nitric oxide, lactate-to-pyruvate ratio, and glycerol in hippocampus and intracranial pressure, but lower values of cerebral perfusion pressure. Agmatine administered immediately after TBI significantly attenuated the TBI-induced increased hippocampal levels of glutamate, nitric oxide, lactate-to-pyruvate ratio, and glycerol, intracranial hypertension, and cerebral hypoperfusion. In addition, the TBI-induced cerebral infarction, motor and proprioception deficits, and body weight loss evaluated 3 days after TBI were significantly attenuated by agmatine therapy. The present data indicate that agmatine may attenuate TBI by reducing the excessive accumulation of both glutamate and nitric oxide in the brain.
AuthorsJinn-Rung Kuo, Chong-Jeh Lo, Chung-Ching Chio, Ching-Ping Chang, Mao-Tsun Lin
JournalResuscitation (Resuscitation) Vol. 75 Issue 3 Pg. 506-14 (Dec 2007) ISSN: 0300-9572 [Print] Ireland
PMID17629391 (Publication Type: Journal Article)
Chemical References
  • Neuroprotective Agents
  • Nitric Oxide
  • Glutamic Acid
  • Agmatine
  • Agmatine (administration & dosage, pharmacology)
  • Animals
  • Brain Injuries (drug therapy, physiopathology)
  • Disease Models, Animal
  • Glutamic Acid (metabolism)
  • Hippocampus (drug effects, physiopathology)
  • Infusions, Parenteral
  • Male
  • Microdialysis
  • Neuroprotective Agents (administration & dosage, pharmacology)
  • Nitric Oxide (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Resuscitation (methods)
  • Time Factors

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