Blood-brain barrier permeability changes during acute allergic encephalomyelitis induced in the guinea pig

Abstract

Blood-brain barrier permeability to homologous serum 125I-IgG and to D-[3H]mannitol was studied by means of the brain vascular perfusion method in guinea pigs with experimental allergic encephalomyelitis (EAE). EAE was induced with homologous myelin basic protein (MBP) after pretreatment with foreign protein and muramyl dipeptide (MDP). The results suggest a significant comparable increase in IgG blood-to-brain clearance in the parietal cortex, hippocampus, and caudate nucleus, during vascular perfusion of the brains of animals, after 7 and 20 days of EAE. On the other hand, unidirectional transfer of mannitol in the same period of EAE was markedly augmented only in the hippocampus, but no significant changes in the parietal cortex or caudate nucleus were observed. Cerebrospinal fluid (CSF)/serum ratios for IgG and albumin were both significantly increased, suggesting an increase in blood-CSF barrier permeability, but more for albumin than for IgG. The results were confirmed by immunohistochemical determination of the IgG deposits in the brains of EAE animals, during vascular perfusion with unlabeled homologous IgG. An important role of the blood-brain barrier for the central nervous system immunoglobulin homeostasis during EAE is suggested.

Profiling and Identification of Cerebrospinal Fluid Proteins in a Rat EAE Model of Multiple Sclerosis

“…It is possible that the permeability of the BBB increases as a result of EAE pathogenesis, leading to the influx of increasingly larger molecules into CSF as the disease progresses to the peak of the clinical symptoms. 25,26 Other studies of the EAE model have shown that whole cells and metalloproteases are transported across the BBB during the peak of the disease, so it is conceivable that other proteins show a similar behavior, as shown in this study. 27,28 Several of the observed discriminatory proteins belong to the class I acute phase proteins, e.g., alpha 1 inhibitor 3, fibrinogen, plasminogen, ceruloplasmin, hemopexin, haptoglobin, alpha 2 macroglobulin, alpha 1 antiproteinase, alpha 1 acid glycoprotein, and the components of the complement system.…”

Angiogenesis in multiple sclerosis and experimental autoimmune encephalomyelitis

“…It can be induced by immunization using antigens derived from myelin. These antigens elicit an acute demyelinating process driven by T cells and macrophages which can have a chronic relapsing course quite similar to MS. Several reports indicate early BBB breakdown in the CNS of EAE [39–44]. Increased vessel density has been documented in different experimental models, including EAE induced in the mouse [40,45,46], guinea pig [47–49], and Lewis rat during the relapse phase [50].…”

Saturable Leptin Transport Across the BBB Persists in EAE Mice

“…For groups receiving 200-fold excess unlabeled leptin in addition to the radioactively labeled proteins, 3 µg of leptin/mouse was included in the 100 µl of injection solution and allowed to incubate for 1 h. Immediately after blood collection by dissection of the right carotid artery 10 min after iv injection, the mice were decapitated. The hippocampus was further dissected from the brain as a focus of the study, based on its known upregulation of astrocytic leptin receptors (Wu et al 2013), impaired BBB functions during EAE (Zlokovic et al 1989), and a main role in sickness behavior (Godbout et al 2008). Cervical spinal cord was separated from the total spinal cord, as it has higher permeability than the thoracic spinal cord during the course of EAE (Pan et al 1996) and is easy to perfuse in the parallel in situ brain perfusion study (shown below).…”