Permeability of cerebral blood vessels in experimental allergic encephalomyelitis studied by radioactive iodinated bovine albumin

Comparison of the timing of acute blood-brain barrier breakdown to rabbit immunoglobulin G in the cerebellum and spinal cord of mice with experimental autoimmune encephalomyelitis

“…2N, arrow) or meninges. This conclusion is in agreement with previous results demonstrating that sodium fluorescein in EAE rabbits induced with rabbit spinal cord (Simmons et al, 1987), and 131 Iodinelabeled albumin in mixed-breed EAE guinea pigs induced with human white matter (Vulpe et al, 1960) cross the BBB at the sites of these leukocytic infiltrates.…”

“…In contrast to this finding, the monocyte/ macrophage infiltration that follows T-cell infiltration in EAE rabbit CNS was always observed to occur with fluorescein leakage through a compromised BBB (Simmons et al, 1987). This suggests that cellular infiltration of the cerebellum may occur with or without changes in the BBB to serum components, depending on the stage of cellular infiltration (Vulpe et al, 1960;Cutler et al, 1967). The present results show that early breakdown of the cerebellar BBB to serum proteins does indeed occur in SJL/J mice induced to develop EAE with PLP 139 -151.…”

“…At disease onset and through the paralysis phase of disease, the BBB in the brain (Vulpe et al, 1960; mixed breed guinea pigs, human white matter: Linthicum et al, 1982; SJL/J X BALB/c and SJL X NZB hybrid mice, mouse spinal cord: Butter et al, 1991;O'Neill et al, 1993; Biozzi AB/H mice, mouse spinal cord: Butter et al, 1991;SJL/JCR mice, PLP 139 -151: Pa et al, 1996) and the cerebellum (Cutler et al, 1967;Leibowitz and Kennedy, 1972;Daniel et al, 1981; Lewis rats, guinea pig spinal cord: Greenlee et al, 1995; Lewis rats, adoptive transfer of MBP-specific lymph node cells: Paul and Bolton, 1995) is compromised, but much less dramatically than in the spinal cord. Studies of the time course of BBB breakdown in EAE mice (Butter et al, 1991) and rats (Oldendorf and Towner, 1974) support a caudal-to-rostral gradient of decreasing disease severity as well as a caudalto-rostral progression of disease, but these studies have not specifically evaluated the cerebellum in a detailed manner.…”

“…Breakdown of the BBB to serum components occurs in EAE just prior to or at the onset of symptomatic neurological disease (Oldstone and Dixon, 1968;Leibowitz et al, 1972;Oldendorf and Towner, 1974;Rumjanek et al, 1984;de Rosbo et al, 1985;Linington et al, 1988;Butter et al, 1991;Greenlee et al, 1995;Paul and Bolton, 1995;Pan et al, 1996) and continues through the paralysis phase of the disease (Vulpe et al, 1960;Linthicum et al, 1982;Lossinsky et al, 1989;O'Neill et al, 1993;Meeson et al, 1994;Greenlee et al, 1995). During remission, the BBB shows a dramatic closing, but it reopens again at relapse (Oldendorf and Towner, 1974;Butter et al, 1991), similar to reports of increased severity of BBB breakdown during MS flares (see above).…”

Study of protein characteristics that influence entry into the cerebrospinal fluid of normal mice and mice with encephalitis.

“…Studies of protein leakage in a variety of traumatic and toxic conditions of the CNS have suggested that protein extravasation occurs between cerebral capillary endothelial cells (3). In acute experimental allergic encephalomyelitis protein leakage from vessels has been observed only in areas with perivascular inflammation (51)(52)(53). It is possible that in a normal animal most of the CSF protein enters by way of the choroid plexus with small amounts from the cerebral capillaries; however during certain CNS inflammatory diseases such as experimental allergic encephalomyelitis or viral encephalitis, there is a substantial amount of protein added by passage across the cerebral capillaries from the blood.…”