ABSTRACT
Oligodendrocytes, the myelin-forming cells of the CNS, exquisitely tailor the thickness of individual myelin sheaths to the diameter of their target axons to maximize the speed of action potential propagation, thus ensuring proper neuronal connectivity and function. Following demyelinating injuries to the adult CNS, newly formed oligodendrocytes frequently generate new myelin sheaths. Following episodes of demyelination such as those that occur in patients with multiple sclerosis, however, the matching of myelin thickness to axon diameter fails leaving remyelinated axons with thin myelin sheaths potentially compromising function and leaving axons vulnerable to damage. How oligodendrocytes determine the appropriate thickness of myelin for an axon of defined size during repair is unknown and identifying the signals that regulate myelin thickness has obvious therapeutic implications. Here, we show that sustained activation of extracellular-regulated kinases 1 and 2 (ERK1/2) in oligodendrocyte lineage cells results in accelerated myelin repair after injury, and is sufficient for the generation of thick myelin sheaths around remyelinated axons in the adult mouse spinal cord. Our findings suggest a model where ERK1/2 MAP kinase signaling acts as a myelin thickness rheostat that instructs oligodendrocytes to generate axon-appropriate quantities of myelin.
Subject(s)
Central Nervous System/pathology , Demyelinating Diseases/pathology , MAP Kinase Signaling System/physiology , Myelin Sheath/pathology , 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase/metabolism , Age Factors , Animals , Animals, Newborn , Basic Helix-Loop-Helix Transcription Factors/metabolism , Demyelinating Diseases/chemically induced , Disease Models, Animal , Glial Fibrillary Acidic Protein/metabolism , MAP Kinase Kinase 1/genetics , MAP Kinase Kinase 1/metabolism , MAP Kinase Signaling System/drug effects , Mice , Mice, Inbred C57BL , Mice, Transgenic , Microscopy, Electron, Transmission , Myelin Sheath/ultrastructure , Nerve Tissue Proteins/metabolism , Oligodendrocyte Transcription Factor 2 , Oligodendroglia/metabolism , Polysaccharides/toxicity , Spinal Cord/metabolism , Spinal Cord/pathology , Up-Regulation/genetics , Up-Regulation/physiologyABSTRACT
PURPOSE: To examine site-specific differences in managing labor and to describe variations in intrapartum practice in the context of clinical midwifery education. DESIGN: Descriptive design based on secondary analysis of an existing data set collected to evaluate the intrapartum clinical experiences of nurse-midwifery students. The data set included 498 records collected by midwifery students in 23 sites from 1995-1998. The unit of analysis was the intrapartum record. METHODS: Students used The American College of Nurse-Midwives Clinical data Set for Intrapartum Care to collect data during clinical experiences, including patient demographic data, risk factors, and specific care processes and interventions. FINDINGS: Significant variations were found among settings despite use of the same clinical guidelines. Discrepancies between theoretical preparation of students for clinical practice and the realities of clinical practice were noted. CONCLUSIONS: Despite a stated commitment to evidence-based practice, practice patterns varied significantly. Clinicians and educators need to find common ground for combining evidence-based theory with evidence-based practice.