Experimental allergic encephalomyelitis in the monkey: humoral immunity and blood-brain barrier function

Abstract

Acute monophasic experimental autoimmune encephalomyelitis (AMEAE) was induced in 5 Macacus cynomolgus monkeys. Serum and cerebrospinal fluid (CSF) paired samples were collected before and four weeks after immunization, time of complete development of AMEAE clinical picture. After immunization the CSF/serum albumin ratio and the IgG index were markedly increased. Agarose isoelectric focusing (AIEF) followed by immunofixation revealed faint IgG oligoclonal bands in both serum and CSF of all monkeys, which became more evident after Kappa and Lambda assessment. Intrathecal synthesis of lgG oligoclonal bands was detected in only one CSFAffinity-driven immunoblotting failed to detect anti-myelin basic protein (MBP) oligoclonal IgG. No free light chain (FLC)patterns or IgA and IgM oligoclonal bands were detected.

Increased Meningeal T and Plasma Cell Infiltration is Associated with Early Subpial Cortical Demyelination in Common Marmosets with Experimental Autoimmune Encephalomyelitis

“…Increased Ig levels were described in the CSF of MS patients and remain a hallmark finding in the diagnosis of MS . Primates with induced EAE also showed an increased IgG concentration in CSF within 4 weeks after immunization .…”

The cerebrospinal fluid immune cell landscape in animal models of multiple sclerosis

“…While these studies did not include naïve animals, CSF leukocytes were likely elevated in comparison to normal ranges of basic immune cells in the Rhesus monkey defined by basic cytology ( Hou et al, 1996 ). Again, however, perplexing variability amongst non-human primate models of MS exists, as cynomolgus monkeys ( Macaca fascicularis ) do not routinely harbor unique OCB within the CSF 4 weeks after immunization with spinal cord homogenate emulsified in CFA ( Gallo et al, 1989 ). While studies of B cells in these higher order models of neuroinflammation add value by uniquely modeling MS, questions regarding intrathecal B cells and immunoglobulin remain incompletely answered.…”

Progress and Prospects for Genetic Modification of Nonhuman Primate Models in Biomedical Research

“…Due to physiologic differences between rodents and higher primates, such as life span (Gilley et al 2011), brain size and complexity (Chen et al 2000;Gilley et al 2011;Hsiao et al 1996;Polymeropoulos et al 1997;Yang et al 2008a) and motor repertoire (Courtine et al 2007;Rice 2012), as well as the availability of cognitive behavioral testing (Bachevalier et al 2011;Bachevalier et al 2001;Bachevalier and Nemanic 2008;Ewing-Cobbs et al 2012), NHPs are considered one of the best animal models; especially for complex disorders that correlate with aging, cognitive behavioral function, mental development, and psychiatric dysfunctions. In addition to neural psychiatric related disorders, metabolic function (Hogstedt et al 1990;O'Sullivan et al 2012;Smith et al 1978), reproductive physiology (Hewitson et al 2002;Kundu et al 2013;Obaldia et al 2011;Wolf 2009), and immunology (Gallo et al 1989;Thomas et al 1982) are other areas of research where the NHP model has been widely used.…”

“…Although the application of NHPs in biomedicine has a decades long history, NHPs have been primarily used in pharmacokinetic (Glogowski et al 2012;Kanazawa et al 1990;Kao et al 2006;King and Dedrick 1979;Liu et al 2009;Lutz et al 1984) and toxicity studies (Jarvis et al 2010;Lee et al 1994), specifically in drug development, physiological response, and efficacy studies of new treatments. Studies on the understanding of normal physiological functions (Gallo et al 1989;Kundu et al 2013;O'Sullivan et al 2012;Wolf 2009) and chemical induced conditions mimicking human disease conditions (Blesa et al 2012;DeLong and Coyle 1979;Vezoli et al 2011) are also areas of research in which the NHP model plays a key role. The creation of the first transgenic NHP in 2001 (Chan et al 2001) and subsequent development of the transgenic NHP model of Huntington's disease (HD) in 2008 (Yang et al 2008a) revolutionized the traditional role of NHPs in biomedicine to the new frontier of modeling human genetic disorders.…”