Cerebral cortex shows a high endogenous propensity for remyelination. Yet, widespread subpial cortical demyelination (SCD) is a common feature in progressive multiple sclerosis (MS) and can already be found in early MS. In the present study, we compared oligodendroglial loss in SCD in early and chronic MS. Furthermore, we addressed in an experimental model whether repeated episodes of inflammatory SCD could alter oligodendroglial repopulation and subsequently lead to persistently demyelinated cortical lesions. NogoA+ mature oligodendrocytes and Olig2+ oligodendrocyte precursor cells were examined in SCD in patients with early and chronic MS, normal-appearing MS cortex, and control cortex as well as in the rat model of repeated targeted cortical experimental autoimmune encephalomyelitis (EAE). NogoA+ and Olig2+ cells were significantly reduced in SCD in patients with chronic, but not early MS. Repeated induction of SCD in rats resulted only in a transient loss of NogoA+, but not Olig2+ cells during the demyelination phase. This phase was followed by complete oligodendroglial repopulation and remyelination, even after four episodes of demyelination. Our data indicate efficient oligodendroglial repopulation in subpial cortical lesions in rats after repeated SCD that was similar to early, but not chronic MS cases. Accordingly, four cycles of experimental de- and remyelination were not sufficient to induce sustained remyelination failure as found in chronic cortical MS lesions. This suggests that alternative mechanisms contribute to oligodendrocyte depletion in chronic cortical demyelination in MS.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-014-1260-8) contains supplementary material, which is available to authorized users.
Adrenal steroid hormones and neuronal growth factors are two interacting systemic factors that mediate the environment's influence on the brain's structure and function. In order to further elucidate their role and relationship in the effects of early stressful experience and isolated rearing (IR), this study measured blood corticosterone titres and relative adrenal weights and assessed nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) concentrations in brain regions of both hemispheres of young adult Mongolian gerbils injected on postnatal day 14 with a single high dose of methamphetamine (MA) or saline and raised after weaning either in an enriched or an impoverished environment. Irrespective of MA challenge, IR decreased corticosterone titres to about half, but increased relative adrenal weights. BDNF concentrations were decreased by IR in saline-injected animals in the left prefrontal and parietal cortices and right entorhinal and hippocampal cortices, and in the subcortical regions of both hemispheres. NGF concentrations were unaltered by IR in saline-injected animals, but increased in MA challenged animals in the entorhinal/hippocampal cortices and subcortical areas of both hemispheres. MA application induced shifts of the lateral asymmetry in NGF contents in prefrontal and entorhinal cortices. The results suggest that an early pharmacological traumatization can set a switch for further brain development, and that growth factor concentrations might possibly be influenced by peripheral stress hormones.
I hereby declare that I wrote this thesis independently and with no other sources and aids than quoted. This thesis has not been submitted elsewhere for any academic degree.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.