TY - JOUR
T1 - Comparison of tirilazad mesylate (U-74006F) and methyl prednisolone sodium succinate treatments in experimental allergic encephalomyelitis in the guinea pig
AU - Karlik, S. J.
AU - Stavraky, R. T.
AU - Hall, E. D.
PY - 1996
Y1 - 1996
N2 - The effects of the non-glucocortioid 21-aminosteroid, tirilazad mesylate (U-74006F), on MRI and clinical findings in guinea pigs with experimental allergic encephalomyelitis were compared to treatment with methylprednisolone sodium succinate (MPSS). A dose response experiment for U-74006F was performed 1, 3 and 10 mg/kg/day 1P on day 0-12 after immunization. Additionally, the 3 mg/kg/day 1P dose was extended to 24 and 35 days. MPSS was given in three different protocols at doses ranging from 0.8 to 3.2 mg/kg/day. Abnormalities in T2-weighted images were assessed as measures of edema and inflammation and gadolinium-DTPA enhanced T1-weighted images were used to determine blood-brain barrier integrity. U-74006F improved the clinical status at doses of 3 and 10 mg/kg. For example, maximum clinical score was halved at 10 mg/ kg/day (P<0.01). The presence of gadolinium-DTPA in the parenchyma was also decreased at 3 and 10 mg/kg/day U-74006F although maximum MRI scores were decreased only in the 10 mg/kg U-74006F group. Clinical disease suppression seen with 3 mg/kg treatment on days 0 - 12 reverted to control at >24 days of dosing. MPSS treatment considerably worsened the clinical outcome of EAE. Mean clinical scores for vehicle and the highest MPSS dose were 0.94±0.66 versus 2.64±1.49 (P<0.05). The combination of decreased T2-weighted abnormalities, clinical signs and gadolinium-DTPA permeation in the U-74006F treated animals suggested protection of the blood-brain barrier without the severe glucocorticoid effects associated with steroid therapy.
AB - The effects of the non-glucocortioid 21-aminosteroid, tirilazad mesylate (U-74006F), on MRI and clinical findings in guinea pigs with experimental allergic encephalomyelitis were compared to treatment with methylprednisolone sodium succinate (MPSS). A dose response experiment for U-74006F was performed 1, 3 and 10 mg/kg/day 1P on day 0-12 after immunization. Additionally, the 3 mg/kg/day 1P dose was extended to 24 and 35 days. MPSS was given in three different protocols at doses ranging from 0.8 to 3.2 mg/kg/day. Abnormalities in T2-weighted images were assessed as measures of edema and inflammation and gadolinium-DTPA enhanced T1-weighted images were used to determine blood-brain barrier integrity. U-74006F improved the clinical status at doses of 3 and 10 mg/kg. For example, maximum clinical score was halved at 10 mg/ kg/day (P<0.01). The presence of gadolinium-DTPA in the parenchyma was also decreased at 3 and 10 mg/kg/day U-74006F although maximum MRI scores were decreased only in the 10 mg/kg U-74006F group. Clinical disease suppression seen with 3 mg/kg treatment on days 0 - 12 reverted to control at >24 days of dosing. MPSS treatment considerably worsened the clinical outcome of EAE. Mean clinical scores for vehicle and the highest MPSS dose were 0.94±0.66 versus 2.64±1.49 (P<0.05). The combination of decreased T2-weighted abnormalities, clinical signs and gadolinium-DTPA permeation in the U-74006F treated animals suggested protection of the blood-brain barrier without the severe glucocorticoid effects associated with steroid therapy.
KW - Experimental allergic encephalomyelitis
KW - MRI
KW - Steroids
KW - Tirilazad
KW - U-74006F
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U2 - 10.1177/135245859600100408
DO - 10.1177/135245859600100408
M3 - Article
C2 - 9345440
AN - SCOPUS:0030072582
SN - 1352-4585
VL - 1
SP - 228
EP - 235
JO - Multiple Sclerosis Journal
JF - Multiple Sclerosis Journal
IS - 4
ER -