Mouse MBP peptide

Background and Purpose White matter injury (WMI) exists in the early stage of subarachnoid hemorrhage (SAH) and has not been well addressed so far. Methods We utilized short hairpin RNA (shRNA) and clustered regularly interspaced short palindromic repeats (CRISPR) to verify the role of peroxisomes in WMI following SAH. We evaluated short- and long-term neurobehavior after SAH. Western blotting, immunofluorescence, and Golgi staining techniques were performed to assess the changes in protein levels. Results Catalase (CAT) CRISPR treatment significantly attenuated neurological deficits and reduced long-term spatial learning and memory impairments after SAH by increasing the level of myelin basic protein (MBP) while decreasing the levels of amyloid precursor protein (APP), interleukin 6 (IL-6), and tumor necrosis factor (TNF)-alpha. The use of thioredoxin-interacting protein (TXNIP) shRNA significantly offset the effects of CAT shRNA, and the use of glycerone phosphate acyl transferase (GNPAT) shRNA significantly reversed the effects of CAT CRISPR by decreasing the levels of plasmalogens and reactive oxidative species (ROS). Conclusion Peroxisomal dysfunction induced by SAH reversely exacerbated cerebral WMI following SAH, which was at least partly mediated by TXNIP and GNPAT pathways.

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 andPAFRconventional knockout (PAFR-KO) mice. Demyelination was induced in cerebellar slices that were cultured with LPC for 18 h. Exogenous PAF (1 mu M) acting on cerebellar slices alone did not cause demyelination but increased the severity of LPC-induced demyelination in both wild-type andPAFR-KO mice. LPC inhibited the expression ofPAF-AH,MBP,TNF-alpha, andTGF-beta 1but facilitated the expression ofIL-1 beta andIL-6in wild-type preparations. Of note, exogenous PAF stimulated microglial activation in both wild-type andPAFR-KO mice. The subsequent inflammatory cytokines TNF alpha, IL-1 beta, and IL-6 as well as the anti-inflammatory cytokine TGF-beta 1 demonstrated a diverse transcriptional profile with or without LPC treatment. PAF promotedTNF-alpha expression and suppressedTGF-beta 1expression indiscriminately in wild-type and knockout slices; however, transcription ofIL-1 beta andIL-6was not significantly affected in both slices. The syntheses ofIL-1 beta andIL-6were 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.