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Hypertension is an important contributor to cognitive decline but the underlying mechanisms are unknown. Although much focus has been placed on the effect of hypertension on vascular function, less is understood of its effects on nonvascular cells. Because astrocytes and parenchymal arterioles (PA) form a functional unit (neurovascular unit), we tested the hypothesis that hypertension‐induced changes...
The role of astrocytes in the pathophysiology of multiple sclerosis (MS) is discussed controversially. Especially the formation of the glial scar is often believed to act as a barrier for remyelination. At the same time, astrocytes are known to produce factors that influence oligodendrocyte precursor cell (OPC) survival. To explore these mechanisms, we investigated the astrocytic reaction in an animal...
Stem/progenitor cell transplantation delivery of astrocytes is a potentially powerful strategy for spinal cord injury (SCI). Axon extension into SCI lesions that occur spontaneously or in response to experimental manipulations is often observed along endogenous astrocyte “bridges,” suggesting that augmenting this response via astrocyte lineage transplantation can enhance axon regrowth. Given the importance...
Optic neuritis is a common manifestation of multiple sclerosis, an inflammatory demyelinating disease of the CNS. Although it is the presenting symptom in many cases, the initial events are currently unknown. However, in the earliest stages of autoimmune optic neuritis in rats, pathological changes are already apparent such as microglial activation and disturbances in myelin ultrastructure of the...
The identification of factors that regulate myelination provides important insight into the molecular mechanisms that coordinate nervous system development and myelin regeneration after injury. In this study, we investigated the role of amyloid precursor protein (APP) and its paralogue amyloid precursor‐like protein 2 (APLP2) in myelination using APP and APLP2 knockout (KO) mice. Given that BACE1...
Accumulating evidence indicates that neuroinflammation contributes to the pathogenesis and exacerbation of neurodegenerative disorders, such as Alzheimer's disease (AD). Sphingosine‐1‐phosphate (S1P) is a pleiotropic bioactive lipid that regulates many pathophysiological processes including inflammation. We present evidence here that the spinster homolog 2 (Spns2), a S1P transporter, promotes microglia...
Patients receiving paclitaxel for cancer treatment often develop an acute pain syndrome (paclitaxel‐associated acute pain syndrome, P‐APS), which occurs immediately after paclitaxel treatment. Mechanisms underlying P‐APS remain largely unknown. We recently reported that rodents receiving paclitaxel develop acute pain and activation of spinal microglial toll like receptor 4 (TLR4) by paclitaxel penetrating...
Emerging evidence indicates that spinal neuroinflammation contributes to the maintenance of chronic inflammatory pain. IL‐36, as a novel member of the interleukin (IL)‐1 super‐family cytokines, plays an important role in inflammatory responses. The present study aimed to investigate the role of spinal IL‐36 and IL‐36 receptor (IL‐36R) signaling in the pathology of chronic inflammatory pain. IL‐36γ...
The microglial triggering receptor expressed on myeloid cells 2 (TREM2) signals via the activatory membrane adaptor molecule TYROBP. Genetic variants or mutations of TREM2 or TYROBP have been linked to inflammatory neurodegenerative diseases associated with aging. The typical aging process goes along with microglial changes and mild neuronal loss, but the exact contribution of TREM2 is still unclear...
Schwann cells respond to nerve injury by cellular reprogramming that generates cells specialized for promoting regeneration and repair. These repair cells clear redundant myelin, attract macrophages, support survival of damaged neurons, encourage axonal growth, and guide axons back to their targets. There are interesting parallels between this response and that found in other tissues. At the cellular...
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