that alter the expression of molecules in cellular activities of cell structure, energy metabolism, intracellular signaling, and membrane transporters and pumps. Reactive astrocytes respond according to different signals and impact neuronal function. Molecular mediators are released by neurons, microglia, oligodendrocyte lineage cells, endothelia, leukocytes, and other astrocytes in the CNS tissue in response to insults ranging from subtle cellular perturbations to intense tissue injury. The resulting effects can range from blood flow regulation to provision of energy to synaptic function and neural plasticity. Signaling molecules Few of the known signaling molecules and their effects are understood in the context of reactive astrocytes responding to different degrees of insult. Upregulation of GFAP, which is induced by FGF, TGFB, and ciliary neurotrophic factor (CNTF), is a classic marker for reactive gliosis. Axon regeneration does not occur in areas with an increase in GFAP and vimentin. Paradoxically, an increase in GFAP production is also specific to the minimization of the lesion size and reduction in the risk for autoimmune encephalomyelitis and stroke. Transporters and channels The presence of astrocyte glutamate transporters is associated with a reduced number of seizures and diminished neurodegeneration whereas the astrocyte gap junction protein Cx43 contributes to the neuroprotective effect of preconditioning to hypoxia. In addition, AQP4, an astrocyte water channel, plays a crucial role in cytotoxic edema and aggravate outcome after stroke. Neurological pathologies Loss or disturbance of functions normally performed by astrocytes or reactive astrocytes during the process of reactive astrogliosis has the potential to underlie neural dysfunction and pathology in various conditions including trauma, stroke, multiple sclerosis, and others. Some of the examples are as follows: Autoimmune destruction of astrocyte endfeet that contact and envelop blood vessels is associated with CNS inflammation and a form of multiple sclerosis Rasmussen's syndrome autoantibody destruction of astrocytes causes seizures In Alexander's disease, a dominant, gain-of-function mutation of the gene encoding GFAP is associated with macro-encephalopathy, seizures, psychomotor disturbances, and premature death. In a familial form of amyotropic lateral sclerosis (ALS), a dominant gain-of-function mutation of the gene encoding superoxide dismutase (SOD) leads to production of reactive astrocytes of molecules that are toxic to motor neurons. Reactive astrocytes may also be stimulated by specific signaling cascades to gain detrimental effects such as the following: Exacerbation of inflammation via cytokine production Production and release of neurotoxic levels of reactive oxygen species Release of potentially excitotoxic glutamate The potential contribution to seizure