DURATION AND SELECTIVITY OF BLOOD-BRAIN BARRIER BREAKDOWN IN CHRONIC RELAPSING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS STUDIED BY GADOLINIUM-DTPA AND PROTEIN MARKERS

Brain ◽  
1990 ◽  
Vol 113 (2) ◽  
pp. 365-378 ◽  
Author(s):  
C. P. HAWKINS ◽  
P. M. G. MUNRO ◽  
F. MACKENZIE ◽  
J. KESSELRING ◽  
P. S. TOFTS ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Experimental Allergic Encephalomyelitis ◽  
Brain Barrier ◽  
Protein Markers ◽  
Allergic Encephalomyelitis ◽  
Gadolinium Dtpa ◽  
Blood Brain ◽  
Barrier Breakdown ◽  
Blood Brain Barrier Breakdown ◽  
Experimental Allergic

Comparison of Tirilazad Mesylate (U-74006F) and Methyl Prednisolone Sodium Succinate Treatments in Experimental Allergic Encephalomyelitis in the Guinea Pig

1996 ◽  
Vol 1 (4) ◽  
pp. 228-235 ◽  
Author(s):  
SJ Karlik ◽  
RT Stavraky ◽  
ED Hall
Keyword(s):  
Blood Brain Barrier ◽  
Experimental Allergic Encephalomyelitis ◽  
Sodium Succinate ◽  
Disease Suppression ◽  
Brain Barrier ◽  
Allergic Encephalomyelitis ◽  
Gadolinium Dtpa ◽  
Blood Brain ◽  
Tirilazad Mesylate ◽  
Experimental Allergic

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 IP on day 0–12 after immunization. Additionally, the 3 mg/kg/day IP 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 TI-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.

scholarly journals A Spatial Analysis of the Blood—Brain Barrier Damage in Experimental Allergic Encephalomyelitis

1985 ◽  
Vol 5 (4) ◽  
pp. 545-553 ◽  
Author(s):  
Marianne Juhler ◽  
Ronald G. Blasberg ◽  
Joseph D. Fenstermacher ◽  
Clifford S. Patlak ◽  
Olaf B. Paulson
Keyword(s):  
Blood Brain Barrier ◽  
Experimental Allergic Encephalomyelitis ◽  
Young Male ◽  
Lymphocytic Infiltration ◽  
Brain Barrier ◽  
Allergic Encephalomyelitis ◽  
Transfer Constant ◽  
Influx Rate ◽  
Blood Brain ◽  
Experimental Allergic

Experimental allergic encephalomyelitis was induced in young male Lewis rats. Following the development of neurological signs, the local distribution of perivascular inflammatory cellular infiltrates and the local blood-to-tissue transfer constants ( K1) of α-aminoisobutyric acid (AIB) were determined, and these results were compared. Perivascular infiltrative lesions were generally found near areas of the CNS that normally lack an effective blood–brain barrier (BBB) such as the choroid plexus and the entry zones of the cranial and spinal nerve roots. This distribution pattern indicates that the entry of the causative agent into CNS tissue may be by way of the permeable microvessels of these structures. In tissue around inflamed veins, the mean transfer constant was slightly but significantly increased (2.8 ± 1.5 μl g−1 min−1) compared with uninvolved regions (0.9 ± 0.2 μl g−1 min−1) and similar areas in control animals (0.9 ± 0.3 μl g−1 min−1). Analysis of the autoradiographic method of determining transfer constants suggested that the AIB influx rate in the lesion areas may actually be manyfold larger than measured, that BBB permeability may be greatly increased at such sites, and that the areas of lymphocytic infiltration and increased K values may be virtually identical.

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