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Introduction: This study was performed to determine whether the disturbed maturation of oligodendrocyte (OL) progenitors might be related to lipopolysaccharide (LPS)-induced hypomyelination., Material and Methods: We created organotypic cultures of forebrain slices from neonatal rats and explored the morphological changes of glial cells expressing tumour necrosis factor  (TNF-) following LPS exposure., Results: We observed marked activation of glial fibrillary acidic protein-positive astrocytes and OX42-positive microglia co-labelled with TNF- four days following LPS exposure. Our results further demonstrated a reduced expression of O4-positive and O1-positive OL progenitors; moreover, we found that their morphologies were suggestive of degeneration (e.g., scanty, rounded bodies with short, fragmented processes and/or cytoplasmic condensation). At seven days following LPS exposure, astrocytes and microglia were still co-labelled for TNF-; however, the expression of O4-positive and O1-positive cells somewhat increased compared to the number observed at 4 days; despite remaining undifferentiated and exhibiting immature morphologies, the cells were likely indicative of regeneration. In contrast, O4-positive and O1-positive cells in controls were well-differentiated, displaying round, thick cell bodies and long, branching processes., Conclusions: In conclusion, maturation arrest and/or under-differentiation of OL progenitors commonly occur during regeneration: they may underlie the degeneration and consequent hypomyelination occurring late after injury, or apoptosis during the acute stage post-injury. Microglia and astrocytes expressing TNF- may also contribute to later myelination failure.

Neurogenesis is a complex and multi-step process of generating completely functional neurons. This process in adult brain is based on pluripotentional neuronal stem cells (NSC), which are able to proliferation and differentiation into mature neurons or glial cells. NSC are located in subgranular zone inside hippocampus and in subventricular zone. The new neurons formation depends on many endo- and exogenous factors which modulate each step of neurogenesis. This article describes the most important regulators of adult neurogenesis, mainly: neurotrophins, growth factors, hormones, neurotransmitters and microenvironment of NSC. Some drugs, especially antipsychotics, antidepressants and normothymics may affect the neurogenic properties of adult brain. Moreover pathological processes such as neuroinflammation, stroke or epilepsy are able to induce proliferation of NSC. The proneurogenic effects of psychotropic drugs and pathological processes are associated with their ability to increase some hormones and neurotrophins level, as well as with rising the expression of antiapoptotic Bcl-2 protein and metalloproteinase MMP-2. Additionaly, some drugs, for example haloperidol, are able to block prolactin and dopaminergic neuroblasts receptors. Down-regulation of adult neurogenesis is associated with alcohol abuse and high stress level. Negative effect of many drugs, such as cytostatics, COX-2 inhibitors and opioides was also observed. The proneurogenic effect of described factors suggest their broad therapeutic potential and gives a new perspective on an effective and modern treatment of many neuropsychiatric disorders. This effect can also help to clarify the pathogenesis of disorders associated with proliferation and degeneration of adult brain cells.

Cytokines, including interleukin-10 (IL-10), are cell signaling molecules taking part in cell‑to‑cell communication, cell proliferation, differentiation, migration and apoptosis. Cytokines also have the ability to induce, regulate, and inhibit inflammation. Cytokines are produced mainly by activated peripheral immune cells, but due to dissemination of the concept of the central nervous system as an immunologically specialized zone, it is considered that cytokine signaling is one of the components of the immune system which can modulate brain functioning. IL-10 shows immunosuppressive properties, and since expression of this cytokine has been shown in the central nervous system, researchers have started to investigate the therapeutic possibilities of IL-10 action in the context of neurodegenerative diseases, which may involve neuroinflammation in their pathogenesis. Recent studies using cell cultures or animal models of neurodegenerative disorders have shown that the importance of IL-10 in the central nervous system goes beyond the anti-inflammatory activity of this cytokine. Involvement of IL-10 in neuroprotection, neurogenesis, regulation of the stress response and hippocampal synaptic plasticity connected with learning and memory is suggested.