The role of
histamine in
edema formation, blood-spinal cord barrier (BSCB) permeability, and spinal cord blood flow (SCBF) following
spinal cord injury (SCI) was examined using modulation of
histamine H1, H2, and
H3 receptors in the rat. Focal
trauma to the spinal cord at the T10-11 level significantly increased spinal cord
edema formation, BSCB permeability to
protein tracers and SCBF reduction in the T9 and T12 segments. Pretreatment with
histamine H1 receptor antagonist mepyramine (1 mg, 5 mg, and 10 mg/kg, i.p.) did not attenuate spinal pathophysiology following SCI. Blockade of
histamine H2 receptors with
cimetidine or
ranitidine (1 mg, 5 mg, or 10 mg/kg 30 minutes before injury) significantly reduced early pathophysiological events in a dose dependent manner. The effects of
ranitidine were far superior to
cimetidine in identical doses. Pretreatment with a
histamine H3 receptor agonist
alpha-methylhistamine (1 mg and 2 mg/kg/i.p.), that inhibits
histamine synthesis and release in the CNS, thwarted
edema formation, BSCB breakdown, and SCBF disturbances after SCI. The lowest dose of
histamine H3 agonist was most effective. Blockade of
histamine H3 receptors with
thioperamide (1 mg, 5 mg/kg, i.p.) exacerbated spinal cord pathology. These observations suggest that stimulation of
histamine H3 receptors and blockade of
histamine H2 receptors is neuroprotective in SCI.