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Accumulating evidence suggests that platelet-activating factor (PAF) increases the inflammatory response in demyelinating diseases such as multiple sclerosis. However, PAF receptor (PAFR) antagonists do not show therapeutic efficacy for MS, and its underlying mechanisms remain poorly understood. In the present study, we investigated the effects of PAF on an ex vivo demyelination cerebellar model following lysophosphatidylcholine (LPC, 0.5 mg/mL) application using wild-type and PAFR conventional knockout (PAFR-KO) mice. Demyelination was induced in cerebellar slices that were cultured with LPC for 18 h. Exogenous PAF (1 μM) acting on cerebellar slices alone did not cause demyelination but increased the severity of LPC-induced demyelination in both wild-type and PAFR-KO mice. LPC inhibited the expression of PAF-AH, MBP, TNF-α, and TGF-β1 but facilitated the expression of IL-1β and IL-6 in wild-type preparations. Of note, exogenous PAF stimulated microglial activation in both wild-type and PAFR-KO mice. The subsequent inflammatory cytokines TNFα, IL-1β, and IL-6 as well as the anti-inflammatory cytokine TGF-β1 demonstrated a diverse transcriptional profile with or without LPC treatment. PAF promoted TNF-α expression and suppressed TGF-β1 expression indiscriminately in wild-type and knockout slices; however, transcription of IL-1β and IL-6 was not significantly affected in both slices. The syntheses of IL-1β and IL-6 were significantly increased in LPC-induced demyelination preparations without PAF but showed a redundancy in PAF-treated wild-type and knockout slices. These data suggest that PAF can play a detrimental role in LPC-induced demyelination probably due to a redundant response of PAFR-dependent and PAFR-independent effects on inflammatory cytokines.

The national incidence of neonatal abstinence syndrome has dramatically increased over the last decade due to an increase in antenatal opioid exposure. Recent human and animal studies suggest that antenatal opioid exposure impacts the developing brain. The purpose of this study is to evaluate the effects of perinatal methadone exposure on myelination in multiple regions in the developing rat brain. Pregnant Sprague-Dawley rats were randomly assigned into three experimental groups and subsequently exposed to drinking water alone or drinking water containing methadone from 7 days post coitum through day 7 or through day 19 after delivery. Two male neonatal rats were randomly selected from each litter and terminated at day 19. The cerebral cortex, hippocampus, cerebellum, and brainstem were dissected and analyzed for three myelin specific proteins - CNP, PLP, and MBP - by Western blot analysis. All pups with exposure to methadone demonstrated decreased expression of CNP, PLP, and MBP in the cerebral cortex and hippocampus. In the cerebellum, PLP expression was down‑regulated without apparent alteration of CNP and MBP expression. PLP and MBP expression, but not CNP expression, were significantly inhibited in the brainstem. Compared to the pups with postnatal methadone exposure via maternal milk through day 7, partial recovery of CNP and PLP expression only occurred in the cerebral cortices of the pups exposed through day 19. The findings show that antenatal opioid exposure in rat pups is associated with regionally‑specific alterations in brain myelination that diversely affects myelin proteins.

Valproic acid (VPA), an anticonvulsant and mood-stabilizing drug, can induce neuronal differentiation, promote neurite extension and exert a neuroprotective effect in central nervous system (CNS) injuries; however, comparatively little is known regarding its action on mouse embryonic neural stem cells (NSCs) and the underlying molecular mechanism. Recent studies suggested that c-Jun N-terminal kinase (JNK) is required for neurite outgrowth and neuronal differentiation during neuronal development. In the present study, we cultured mouse embryonic NSCs and treated the cells with 1 mM VPA for up to 7 days. The results indicate that VPA promotes the neuronal differentiation of mouse embryonic NSCs and neurite outgrowth of NSC-derived neurons; moreover, VPA induces the phosphorylation of c-Jun by JNK. In contrast, the specific JNK inhibitor SP600125 decreased the VPA-stimulated increase in neuronal differentiation of mouse embryonic NSCs and neurite outgrowth of NSC-derived neurons. Taken together, these results suggest that VPA promotes neuronal differentiation of mouse embryonic NSCs and neurite outgrowth of NSC-derived neurons. Moreover, JNK activation is involved in the effects of VPA stimulation.

The chemokine CXCL12 plays a vital role in regulating the development of the central nervous system (CNS) by binding to its receptors CXCR4 and CXCR7. Recent studies reported that the CXCL12/CXCR4/CXCR7 axis regulates both embryonic and adult oligodendrocyte precursor cells (OPCs) in their proliferation, migration, and differentiation. The changes in the expression and distribution of CXCL12 and its receptors are tightly associated with the pathological process of demyelination in multiple sclerosis (MS), suggesting that modulating the CXCL12/CXCR4/CXCR7 axis may benefit myelin repair by enhancing OPC recruitment and differentiation. This review aims to integrate the current findings of the CXCL12/CXCR4/CXCR7 signaling pathway in the CNS and to highlight its role in oligodendrocyte development and demyelinating diseases. Furthermore, this review provides potential therapeutic strategies for myelin repair by analyzing the relevance between the pathological changes and the regulatory roles of CXCL12/CXCR4/CXCR7 during MS.

Neural stem cells (NSCs) are characterized by their potential for self-renewal and ability to differentiate into neurons, astrocytes, and oligodendrocytes. They are of great value to scientific studies and clinical applications. Culturing NSCs in vitro is important for characterizing their properties under controlled environmental conditions that may be modified and monitored accurately. The present study explored a modified, detailed and efficient protocol for the isolation, culture and cryopreservation of rat embryonic NSCs. In particular, the viability, nestin expression, and self-renewal and multi-differentiation capabilities of NSCs cryopreserved for various periods of time (7 days, or 1, 6 or 12 months) were characterized and compared. Rat embryonic NSCs were successfully obtained and maintained their self-renewal and multipotent differentiation capabilities even following long-term cryopreservation (for up to 12 months).

Background Spinal cord injury (SCI) is a disease associated with high disability and mortality rates. The transitional phase from subacute phase to intermediate phase may play a major role in the process of secondary injury. Changes in protein expression levels have been shown to play key roles in many central nervous system (CNS) diseases. Nevertheless, the roles of proteins in the transitional phase of SCI are not clear. Methods We examined protein expression in a rat model 2 weeks after SCI and identified differentially expressed proteins (DEPs) using isobaric tagging for relative and absolute protein quantification (iTRAQ). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEPs were performed. Furthermore, we constructed a protein-protein interaction (PPI) network, and the top 10 high-degree core nodes were identified. Meanwhile, we validated protein level changes of five high-degree core regulated proteins using Western blots. Results A total of 162 DEPs were identified between the injury group and the control, of which 101 (62.35%) were up-regulated and 61 (37.65%) were down-regulated in the transitional phase of SCI. Key molecular function, cellular components, biological process terms and pathways were identified and may be important mechanisms in the transitional phase of SCI. Alb, Calm1, Vim, Apoe, Syp, P4hb, Cd68, Eef1a2, Rab3a and Lgals3 were the top 10 high-degree core nodes. Western blot analysis performed on five of these proteins showed the same trend as iTRAQ results. Conclusion The current study may provide novel insights into how proteins regulate the pathogenesis of the transitional phase after SCI.

Platelet-activating factor (PAF) is a bioactive lipid mediator which serves as a reciprocal messenger between the immune and nervous systems. PAF, a pluripotent inflammatory mediator, is extensively expressed in many cells and tissues and has either beneficial or detrimental effects on the progress of inflammation-related neuropathology. Its wide distribution and various biological functions initiate a cascade of physiological or pathophysiological responses during development or diseases. Current evidence indicates that excess PAF accumulation in CNS diseases exacerbates the inflammatory response and pathological consequences, while application of PAF inhibitors or PAFR antagonists by blocking this signaling pathway significantly reduces inflammation, protects cells, and improves the recovery of neural functions. In this review, we integrate the current findings of PAF signaling in CNS diseases and elucidate topics less appreciated but important on the role of PAF signaling in neurological diseases. We propose that the precise use of PAF inhibitors or PAFR antagonists that target the specific neural cells during the appropriate temporal window may constitute a potential therapy for CNS diseases.