A major impediment to CNS repair is the glial scar, which forms following damage and is composed mainly of ramified, 'reactive' astrocytes that inhibit neuronal regrowth. The transition of astrocytes into this reactive phenotype (reactive gliosis) is a potential therapeutic target, but glial scar formation has proved difficult to study in monolayer cultures because they induce constitutive astr...

The adult mammalian brain responds to injury by activating a program of cell proliferation during which many oligodendrocyte precursors, microglia, and some astrocytes proliferate. Another common response to brain injury is the induction of reactive gliosis, a process whereby dormant astrocytes undergo morphological changes and alter their transcriptional profiles. Although brain injury-induced...

Reactive astrogliosis is an essential and ubiquitous response to CNS injury, but in some cases, aberrant activation of astrocytes and their release of inhibitory signaling molecules can impair endogenous neural repair processes. Our lab previously identified a secreted intercellular signaling molecule, called endothelin-1 (ET-1), which is expressed at high levels by reactive astrocytes in multi...

Understanding how the transcription factor signal transducer and activator of transcription-3 (STAT3) controls glial scar formation may have important clinical implications. We show that astrocytic STAT3 is associated with greater amounts of secreted MMP2, a crucial protease in scar formation. Moreover, we report that STAT3 inhibits the small GTPase RhoA and thereby controls actomyosin tonus, a...

Factors that regulate leukocyte entry and spread through CNS parenchyma during different types of CNS insults are incompletely understood. Reactive astrocytes have been implicated in restricting the spread of leukocytes from damaged into healthy parenchyma during the acute and local innate inflammatory events that follow CNS trauma, but the roles of reactive astrocytes during the chronic and wi...

Background: Following spinal cord injury, reactive astrocytes upregulate chondroitin sulfate proteoglycans (CSPGs) which act as a barrier to neuronal repair and regeneration. Therefore, enzymatic digestion of CSPGs by chondroitinase ABC (cABC) is a key strategy in the treatment of spinal cord injury. Furthermore, cABC has been shown to attenuate post spinal cord injury inflamma...

Chondroitin sulfate proteoglycans (CS-PGs) expressed by reactive astrocytes may contribute to the axon growth-inhibitory environment of the injured CNS. The specific potentially inhibitory CS-PGs present in areas of reactive gliosis, however, have yet to be thoroughly examined. In this study, we used immunohistochemistry, combined immunohistochemistry-in situ hybridization, immunoblot analysis,...

Toxoplasma gondii is an obligate intracellular parasite that is a common opportunistic pathogen of the central nervous system in AIDS patients. Gamma interferon (IFN-gamma) alone or in combination with interleukin-1 (IL-1), IL-6, or tumor necrosis factor alpha significantly inhibits the growth of T. gondii in murine astrocytes, suggesting these are important nonimmune effector cells in the brai...

The immunohistochemical expression of glial fibrillary acidic protein (GFAP) and vimentin (VIM) was studied in reactive astrocytes of the rat cerebral cortex 5 days after a brain injury. Seriated Epon semithin sections were immunostained alternatively for GFAP or VIM. Thereafter, both antigens were detected in consecutive sections of the same cell. Bordering the wound, an inner reactive glial l...

The roles that astrocytes play in the evolution of abnormal network excitability in chronic neurological disorders involving brain injury, such as acquired epilepsy, are receiving renewed attention due to improved understanding of the molecular events underpinning the physiological functions of astrocytes. In epileptic tissue, evidence is pointing to enhanced chemical signaling and disrupted li...