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

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 IgG oligoclonal bands was detected in only one CSF. Affinity-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.

Tumor necrosis factor alpha (TNF alpha) and neurological diseases. Failure in detecting TNF alpha in the cerebrospinal fluid from patients with multiple sclerosis, AIDS dementia complex, and brain tumours.

The presence of tumor necrosis factor alpha (TNF alpha)/cachectin was investigated in 180 paired cerebrospinal fluid (CSF) and serum samples from patients with neurological diseases, and in five paired CSF and serum samples of Macaca cynomolgus monkeys with acute monophasic experimental autoimmune encephalomyelitis (AMEAE). TNF alpha was never detected in human CSF, even when an extensive demyelination was documented (active multiple sclerosis, acquired immunodeficiency syndrome (AIDS) dementia complex). Only one Macaca with AMEAE had detectable levels of TNF alpha in CSF but not in serum, suggesting an intrathecal synthesis of this cytokine in AMEAE.

Serum lipids and demyelination in experimental allergic encephalomyelitis induced by the increased encephalitogenicity of myelin basic protein given with galactocerebrospide.

Cholesterol esters and free cholesterol were determined in the serum of guinea pigs with experimental allergic encephalomyelitis (EAE). EAE was induced by immunization with myelin basic protein (MBP) and galactocerebroside (GC). The results showed an increased content of cholesterol arachidonate and cholesterol linoleate during the period of clinical signs of EAE in comparison with the content of cholesterol esters in EAE induced by MBP without galactocerebroside. The content of free cholesterol was significantly reduced. Histological analyses showed intensive inflammatory lesions and demyelination which were not found in EAE induced by MBP without galactocerebroside.

Prealbumin content of cerebrospinal fluid and sera in persons with multiple sclerosis.

The prealbumin content of cerebrospinal fluid (CSF) and serum of patients with multiple sclerosis (MS) was determined. Prealbumin was determined, quantitatively in unconcentrated CSF and serum by Laurell's rocket immunoelectrophoresis. The values of serum prealbumin content were normal. An increased prealbumin content was found in the CSF of patients. With other laboratory examinations, the increased CSF prealbumin content may contribute to the diagnosis of MS.

The levels of free cholesterol and cholesterol esters in serum before, during and after the induction of experimental allergic encephalomyelitis in the guinea-pig.

Cholesterol esters and free cholesterol were determined in the serum of guinea-pigs with experimental allergic encephalomyelitis (EAE). EAE was induced by immunization with myelin basic protein (MBP). The results showed a marked decrease in cholesterol esters (CHE) 4 days after immunization. Seven days after immunization the values of esters increased and reached a maximum during the period of manifest clinical signs of EAE. After the cessation of clinical signs, after 2 weeks, the values of esters returned to the initial or somewhat lower values. The level of cholesterol was inverse to the values of cholesterol esters. Histological analyses showed characteristic changes in the brain and spinal cord. A possible correlation between the changes in cholesterol esters and cholesterol of the brain and serum in EAE is suggested.

Compartmentation of glutamate metabolism in brain. Evidence for the existence of two different tricarboxylic acid cycles in brain.

1. (14)C from [1-(14)C]glucose injected intraperitoneally into mice is incorporated into glutamate, aspartate and glutamine in the brain to a much greater extent than (14)C from [2-(14)C]glucose. This difference for [1-(14)C]glucose and [2-(14)C]glucose increases with time. The amount of (14)C in C-1 of glutamate increases steadily with time with both precursors. It is suggested that a large part of the glutamate and aspartate pools in brain are in close contact with intermediates of a fast-turning tricarboxylic acid cycle. 2. (14)C from [1-(14)C]acetate and [2-(14)C]acetate is incorporated to a much larger extent into glutamine than into glutamate. An examination of the time-course of (14)C incorporated into glutamine and glutamate reveals that glutamine is not formed from the glutamate pool, labelled extensively by glucose, but from a small glutamate pool. This small glutamate pool is not derived from an intermediate of a fast-turning tricarboxylic acid cycle. 3. It is proposed that two different tricarboxylic acid cycles exist in brain.