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Show 92 et al., 2015). Nevertheless, vesicular release has not been demonstrated in vivo and may represent an astrocytic culture-specific or a pathological phenomenon (Vardjan et al., 2015). Most gliotransmitter release studies have been performed in astrocytic cultures and support the idea that astrocytes can release glutamate, ATP and D-serine in a vesicular dependent fashion (Henneberger et al., 2010; Jourdain et al., 2007; Parpura et al., 2011). The results have never been replicated in vivo, however, suggesting the possibility that vesicular release is an artifact of dedifferentiation induced by the culturing procedure. An intriguing, but speculative and untested, hypothesis is that vesicular release occurs only in highly reactive astrocytes with, cultured astrocytes serving as a prominent example. Thus, one can speculate that such release may occur in other conditions that induced reactive astrocytosis, including epilepsy. Reactive astrocyte physiology Although the existence of reactive astrocytosis has been known for over 100 years, the definition of is still unclear. Traditionally, reactive astrocytes have been identified by increased expression of GFAP and morphological changes. However, it appears that astrocytes respond to different types of insults in different ways and in a graded fashion (Sofroniew, 2009). In mild cases, morphological alterations and loss of domain organization may not be apparent whereas in severe cases, proliferation and scar formation may occur that is observable with the naked eye. Functional of reactive astrocytes are not well understood and do not necessarily reflect morphological alterations. A negative view of astrocytosis is derived from the traditional view that it inhibits axon regeneration and impairs the brains ability to heal. However, there are many |