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376
Abstracts
SY-16-5
New concepts in the immunopathogenesis of central
nervous system (CNS) infections
P.K. Peterson, S. Hu, G. Gekker, W.S. Sheng, M.C.-J.
Cheeran, J.R. Lokensgard
Neuroimmunology Laboratory, Minneapolis Medical
Research Foundation, and the University of Minnesota
Medical School, Minneapolis, MN, USA
Despite the emergence of new etiologies and the serious
nature of encephalitis, little is known about the cellular and
molecular mechanisms involved in defense and neuropathogenesis
of infections within the brain. To address
this void in knowledge, research in our laboratory has
focused on interactions between neurotropic agents and
homogeneous populations of microglia, the resident macrophages
of the brain, astrocytes, the predominant brain cell
type, and highly enriched neurons. We have studied a variety
of intracellular pathogens including HIV-1, the etiologic
agent of AIDS dementia, cytomegalovirus, an
important cause of congenital brain disease and of encephalitis
in immunocompromised patients, and herpes
simplex virus (HSV)-1 which causes a devastating encephalitis
in immunocompetent individuals. Striking differences
have been found in the growth characteristics and in
the induction of cytokines and chemokines by these viruses
in microglia, astrocytes, and neurons. While several proinflammatory
cytokines can inhibit viral replication in glial
cells and neurons, the inability of brain cells to produce
interferon represents a major defect in host defense of the
brain. To solve this deficiency, it appears that chemokines
are used to attract CD4 1 and CD8 1 lymphocytes into the
infected brain. While this strategy may lead to resolution of
infection, in HSV-1 encephalitis it appears that ingress of
activated T-cells contributes to immune-mediated brain
damage. These concepts of the brain as an ‘immunologically
underprivileged site’ and of microglia and T-cells as
‘double-edged swords’ may guide development of new
therapeutic approaches to CNS infections.
MORNING SEMINAR
MS-1
Nutrition and Developing Brain
MS-01
Nutrition and the developing brain: the role of
polyunsaturated fatty acids
B. Koletzko
University of Munich, Germany
Intrauterine and early postnatal growth is characterised
by a very rapid deposition of lipids. The brain, retina and
other membrane rich tissues rapidly incorporate long-chain
polyunsaturated fatty acids (LCPUFA), especially docosahexaenoic
acid (DHA, C22:6n-3). In utero, the foetus is
supplied with preformed LCPUFA by placental transfer.
After birth, breast fed infants receive appreciable amounts
of preformed LCPUFA that meet intrauterine accretion
rates in membrane rich tissues. Stable isotope studies
show that human milk LCPUFA contents are not primarily
regulated by maternal tissues and not maternal diet. In
contrast, infant formulas based on vegetable oils did not
contain LCPUFA. Term infants fed formulas without
LCPUFA show a LCPUFA depletion in blood and tissues,
including the brain. Several studies have evaluated the
supplementation of infant formulas with different sources
of LCPUFA, which may normalise LCPUFA status relative
to reference groups fed human milk. Double blind
randomised trials demonstrated that LCPUFA induce
significant improvements of visual acuity and a variety
of measures of cognitive development (Bayley, Fagan,
Brunet-Lezine, and others). Our recent studies in children
with phenylketonuria indicate that DHA modulates brain
function also during school age. From the available data
we conclude that LCPUFA are conditionally essential
substrates in infants and children that modulate visual
and cognitive function.
MS-2
Peripheral Neuropathy
MS-02-1
Progressive understanding on the pathogenesis of
Guillain-Barré syndrome
F.-C. Cai
Department of Neurology, Children’s Hospital, Chongqing
University of Medical Sciences, Chongqing, China
Guillain-Barré syndrome (GBS) is an acute autoimmune
polyneuropathy and currently is recognized as a heterogeneous
disorder with several different subtypes including
acute inflammatory demyelinating polyneuropathy
(AIDP), acute motor axonal neuropathy (AMAN),acute
motor-sensory axonal neuropathy (AMSAN), and Miller-
Fisher syndrome, etc. Patients usually have antecedent
events (an illness of respiratory or gastrointestinal tract in
most), however recently there are strong evidences
supporting that at least 30–40% of GBS patients are
infected with Campylobacter jejuni prior to the onset of
the disorder in 2 weeks. Infection by C. jejuni or other
organisms may trigger an antibody response in patients
with GBS but not in those uncomplicated cases. Most
current studies of pathogenesis are centered on the hypothesis
of molecular mimicry between LPS of C. jejuni and
epitopes of host’s nerve gangliosides. Antibodies to ganglioside
GM 1 are present in 14–50% of GBS patients, but
more common in cases with axonal degeneration associated
with any subtype. Antibodies to ganglioside GQ1b
are very closely associated with Fisher syndrome. However