Dynamics of Cerebral Function in Patients with Acute Cerebellar Infarction.

Few studies were devoted to investigating cerebral functional changes after acute cerebellar infarction (CI). The purpose of this study was to examine the brain functional dynamics of CI using electroencephalographic (EEG) microstate analysis. And the possible heterogenicity in neural dynamics between CI with vertigo and CI with dizziness was explored. Thirty-four CI patients and 37 age- and gender-matched healthy controls(HC) were included in the study. Each included subject underwent a 19-channel video EEG examination. Five 10-s resting-state EEG epochs were extracted after data preprocessing. Then, microstate analysis and source localization were performed using the LORETA-KEY tool. Microstate parameters such as duration, coverage, occurrence, and transition probability are all extracted. The current study showed that the duration, coverage, and occurrence of microstate(Ms) B significantly increased in CI patients, but the duration and coverage of MsA and MsD decreased. Compared CI with vertigo to dizziness, finding a decreased trend in the coverage of MsD and the transition from MsA and MsB to MsD. Taken together, our study sheds new light on the dynamics of cerebral function after CI, mainly reflecting increased activity in functional networks involved in MsB and decreased activity in functional networks involved in MsA and MsD. Vertigo and dizziness post-CI may be suggested by cerebral functional dynamics. Further longitudinal studies are needed to validate and explore the alterations in brain dynamics to what extent depict the clinical traits and their potential applications in the recovery of CI.

Olig2 Ablation in Immature Oligodendrocytes Does Not Enhance CNS Myelination and Remyelination.

The oligodendrocyte (OL) lineage transcription factor Olig2 is expressed throughout oligodendroglial development and is essential for oligodendroglial progenitor specification and differentiation. It was previously reported that deletion of Olig2 enhanced the maturation and myelination of immature OLs and accelerated the remyelination process. However, by analyzing multiple Olig2 conditional KO mouse lines (male and female), we conclude that Olig2 has the opposite effect and is required for OL maturation and remyelination. We found that deletion of Olig2 in immature OLs driven by an immature OL-expressing Plp1 promoter resulted in defects in OL maturation and myelination, and did not enhance remyelination after demyelination. Similarly, Olig2 deletion during premyelinating stages in immature OLs using Mobp or Mog promoter-driven Cre lines also did not enhance OL maturation in the CNS. Further, we found that Olig2 was not required for myelin maintenance in mature OLs but was critical for remyelination after lysolecithin-induced demyelinating injury. Analysis of genomic occupancy in immature and mature OLs revealed that Olig2 targets the enhancers of key myelination-related genes for OL maturation from immature OLs. Together, by leveraging multiple immature OL-expressing Cre lines, these studies indicate that Olig2 is essential for differentiation and myelination of immature OLs and myelin repair. Our findings raise fundamental questions about the previously proposed role of Olig2 in opposing OL myelination and highlight the importance of using Cre-dependent reporter(s) for lineage tracing in studying cell state progression.SIGNIFICANCE STATEMENT Identification of the regulators that promote oligodendrocyte (OL) myelination and remyelination is important for promoting myelin repair in devastating demyelinating diseases. Olig2 is expressed throughout OL lineage development. Ablation of Olig2 was reported to induce maturation, myelination, and remyelination from immature OLs. However, lineage-mapping analysis of Olig2-ablated cells was not conducted. Here, by leveraging multiple immature OL-expressing Cre lines, we observed no evidence that Olig2 ablation promotes maturation or remyelination of immature OLs. Instead, we find that Olig2 is required for immature OL maturation, myelination, and myelin repair. These data raise fundamental questions about the proposed inhibitory role of Olig2 against OL maturation and remyelination. Our findings highlight the importance of validating genetic manipulation with cell lineage tracing in studying myelination.