gain of detrimental ones. in this light, gliosis may be seen not only as a characteristic of many neuropathologies but as a potential contributor to, or even cause of, many cns disease mechanisms. a select group of cns conditions associated with gliosis are described below. cns trauma acute trauma to the brain or spinal cord results in gliosis, most often in its severe form with the development of a glial scar. different locations around the lesion site may exhibit different severities of gliosis; for example, a glial scar at the location of damaged tissue may be surrounded by areas with less severe astrocyte proliferation or hypertrophy. diffuse traumatic injury can result in diffuse or more moderate gliosis without scar formation. in such cases, gliosis may also be reversible. in all instances of gliosis resulting from cns trauma, the long-term clinical outcome is highly dependent on the degree of astrogliosis and scar formation. multiple sclerosis and autoimmune inflammatory disorders gliosis is a prominent feature of many autoimmune inflammatory disorders, notably multiple sclerosis, in which demyelinated plaques are surrounded by reactive astrocytes. these astrocytes often exhibit extreme hypertrophy and multiple distinct nuclei, and their production of pro-inflammatory molecules has been implicated in several inflammatory disorders. cytokines produced by both active astrocytes and microglia in inflammatory conditions may contribute to myelin damage and may alter blood-brain barrier permeability, allowing the migration of lymphocytes into the cns and heightening the autoimmune attack. retinal gliosis in vertebrates, the retina contains müller cells, a type of glia not found elsewhere in the cns. upon retinal injury, gliosis of these cells occurs, functioning to repair damage, but often having harmful consequences in the process, worsening some of the diseases or problems that initially trigger it. reactive gliosis in the retina can have detrimental effects on vision; in particular, the production of proteases by astrocytes causes widespread death of retinal ganglion cells. a 2011 study compared the effects of two glial toxins, aaa and neurostatin, on retinal gliosis in mice. aaa did not inhibit the production of protease by astrocytes, and so did not prevent ganglion cell apoptosis. however, neurostatin successfully inhibited activation of astrocytes, in turn decreasing retinal ganglion cell death significantly. neurostatin is also effective in the inhibition of other glial cells, and may be an area of interest in the treatment of degenerative diseases such as glaucoma. massive retinal gliosis (mrg) is a phenomenon in which the retina is completely replaced by proliferation of glial cells, causing deterioration of vision and even blindness in some cases. sometimes mistaken for an intraocular tumor, mrg can arise from a neurodegenerative disease, congenital defect, or from trauma to the eyeball, sometimes appearing years after such an incident. alzheimer's disease gliosis has long been known as a characteristic of alzheimer's disease (ad), although its exact role in the disease remains unknown. gliosis and glial scarring occur in areas surrounding the amyloid plaques which are hallmarks of the disease, and postmortem tissues have indicated a correlation between the degree of astrogliosis and cognitive decline. exposure of reactive astrocytes to β-amyloid (αβ) peptide, the main component of amyloid plaques, may also induce astroglial dysfunction and neurotoxicity. in addition, the ability of reactive astrocytes to degrade extracellular αβ deposits may suggest that astrogliosis may affect the progression or severity of ad. amyotrophic lateral sclerosis amyotrophic lateral sclerosis (als) is a debilitating disease involving the degeneration of motor neurons in the cns. reactive astrocytes have been implicated in this condition through either a loss of their neuroprotective ability or through the gain of neurotoxic effects. late stages of als are also characterized by significant astrogliosis and astrocyte proliferation around areas of degeneration. potential therapeutic targets in gliosis the implications of gliosis in various neuropathologies and injury conditions has led to the investigation of various therapeutic routes which would regulate specific aspects of gliosis in order to improve clinical outcomes for both cns trauma and a wide range of neurological disorders. because gliosis is a dynamic process which involves a spectrum of changes depending on the type and severity of the initial insult, to date, no single molecular target has been identified which could improve healing in all injury contexts. rather, therapeutic strategies for minimizing the contribution of astrogliosis to cns pathologies must be designed to target specific molecular pathways and responses. one promising therapeutic mechanism is the use of β-lactam antibiotics to enhance the glutamate uptake of astrocytes in order to reduce excitotoxicity and provide neuroprotection in models of stroke and als. other proposed targets related to astrogliosis include manipulating aqp4 channels, diminishing the action of nf-kb, or regulating the stat3 pathway in order to reduce the inflammatory effects of reactive astrocytes. astrogliosis may also be attenuated by inhibiting the microgliosis response. one notable microglial activation inhibitor is minocycline, which is a known suppressor of astrogliosis. the cell cycle inhibitor olomoucine also has been shown to suppress both microglial and astroglial proliferation as well as glial scar formation. future directions for identifying novel therapeutic strategies must carefully account for the complex array of factors and signaling mechanisms driving the gliosis response, particularly in different stages after damage and in different lesion conditions.