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.