Multiple sclerosis (MS) is a lifelong inflammatory demyelinating disease of the central nervous system (CNS). While there has been substantial progress in the development of therapeutic strategies for relapsing disease, the field has lagged behind in its understanding and management of progressive stages of the disease, including secondary progressive and primary progressive MS, respectively. It is now thought that distinct but temporally overlapping mechanisms underlie relapsing and progressive aspects of the disease. Relapsing disease is characterized by waves of peripheral immune cell activation and CNS infiltration leading to focal destruction of the white matter, while progressive disease is thought to be driven by chronic, low-grade multifocal inflammation contained within the CNS compartment. Specifically, peripheral B cells, T cells, and myeloid cells take up residence within niches of the inflamed CNS, such as the leptomeninges and the Virchow-Robin spaces, where complex interactions between peripheral and CNS resident cells serve to maintain these cellular aggregates and further propagate CNS injury. In particular, immune infiltrates within the meninges are tightly associated with a specific form of cortical injury, termed subpial cortical demyelination, which is thought to be a key pathologic driver of disease progression. Cortical injury in the MS brain likely occurs via a combination of multiple immune-mediated and degenerative processes, perhaps including the production of diffusible toxic mediators by peripheral immune cells retained within the meninges. A better understanding of the interplay between peripheral immune and CNS resident cells is not only relevant to our concept of the disease process, but also represents a novel target for therapeutic intervention that is more specific to progressive disease biology. This review will focus on the role of CNS-compartmentalized inflammation in the development of cortical injury in MS, with a particular emphasis on the importance of immune-CNS crosstalk in disease progression.
Spinal cord injury (SCI) is a debilitating injury that results from traumatic or non-traumatic insults to the spinal cord, causing significant impairment of the patient's activity and quality of life. Bone morphogenic proteins (BMPs) are a group of polyfunctional cytokines belonging to the transforming growth factor beta superfamily that regulates a wide variety of cellular functions in healthy and disease states. Recent studies suggest that dysregulation of BMP signaling is involved in neuronal demyelination and death after traumatic SCI. The focus of this article is to describe our current understanding of the role of BMP signaling in the regulation of cell fate, proliferation, apoptosis, autophagy, and inflammation in traumatic SCI. First, we will describe the expression of BMPs and pattern of BMP signaling before and after traumatic SCI in rodent models and in vitro. Next, we will discuss the role of BMP in the regulation of neuronal and glial cell differentiation, survival, functional recovery from traumatic SCI, and the gap in knowledge in this area that requires further investigation to improve SCI prognosis.
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