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Astrocytes have not been a major therapeutic target for the treatment of stroke, with most research emphasis on the neuron. Given the essential role that astrocytes play in maintaining physiological function of the central nervous system and the very rapid and sensitive reaction astrocytes have in response to cerebral injury or ischemic insult, we propose to replace the neurocentric view for treatment...
A flurry of studies over the past decade has shown that astrocytes play a more active role in neural function than previously recognized. Hippocampal slices prepared from young rodent pups have served as a popular model for studying the pathways by which astrocytes participate in synaptic transmission. It is, however, not known how well astrocytes tolerate traumatic injury and hypoxia, which are unavoidable...
Nijmegen Breakage Syndrome (NBS) is a recessive genetic disorder characterized by immunodeficiency, elevated sensitivity to ionizing radiation, chromosomal instability, microcephaly, and high predisposition to malignancies. Since the underlying molecular mechanisms of the NBS microcephaly are still obscure, thus our group previously inactivated the Nbn gene in the central nervous system (CNS) of mice...
Microglia cells function as sentinels for innate immunity in the central nervous system (CNS). To perform this function, microglia express a diverse set of pattern recognition receptors (PRRs) for pathogen‐associated molecular patterns (PAMPs) that include Toll‐like receptors (TLRs) and inflammasomes. Several members of the TLR and inflammasome family also recognize endogenously derived molecules...
Microglia are the resident immune cells and phagocytes of our central nervous system (CNS). While most work has focused on the rapid and robust responses of microglia during CNS disease and injury, emerging evidence suggests that these mysterious cells have important roles at CNS synapses in the healthy, intact CNS. Groundbreaking live imaging studies in the anesthetized, adult mouse demonstrated...
Microglia, macrophages of the central nervous system, play an important role in brain homeostasis. Their origin has been unclear. Recent fate‐mapping experiments have established that microglia mostly originate from Myb‐independent, FLT3‐independent, but PU.1‐dependent precursors that express the CSF1‐receptor at E8.5 of embryonic development. These precursors are presumably located in the yolk sac...
MicroRNAs (miRNAs) are a class of small (∼22 nucleotides) noncoding RNAs involved in the regulation of gene expression at the post‐translational level. It is estimated that 30–90% of human genes are regulated by miRNAs, which makes these molecules of great importance for cell growth, activation, and differentiation. Microglia is CNS‐resident cells of a myeloid lineage that play an important role in...
It is well accepted that CNS inflammation has a role in the progression of chronic neurodegenerative disease, although the mechanisms through which this occurs are still unclear. The inflammatory response during most chronic neurodegenerative disease is dominated by the microglia and mechanisms by which these cells contribute to neuronal damage and degeneration are the subject of intense study. More...
The arcuate nucleus (ARC) of the hypothalamus plays a key role in sensing metabolic feedback and regulating energy homeostasis. Recent studies revealed activation of microglia in mice with high‐fat diet (HFD)‐induced obesity (DIO), suggesting a potential pathophysiological role for inflammatory processes within the hypothalamus. To further investigate the metabolic causes and molecular underpinnings...
Oligodendrocytes (OLGs) produce and maintain myelin in the central nervous system (CNS). In the demyelinating autoimmune disease multiple sclerosis, OLGs are damaged and those remaining fail to fully remyelinate CNS lesions. Therefore, current therapies directed to restrain the inflammation process with approaches that protect and reconstitute oligodendrocyte density would be essential to pave the...
Many pathological processes within the central nervous system are mediated by complex interactions between neurons and resident glial cells. In the case of painful peripheral neuropathy, spinal microglia react and undergo a series of changes that directly influence the establishment of neuropathic pain states. Purinergic signaling has been shown to be at the center of this reactivity, and here we...
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