Acta Neuropathol (2010) 119:7–35 estimate how long it occurred prior to death), though not very accurately. The sequence of cellular events in an ischemic infarct progresses from intense neuronal eosino- philia (hours to 1–2 days after the insult), to inﬂux of polymorphonuclear leukocytes (variable intensity, but usually within the same time frame), then ingress of macrophages/histiocytes (from blood or activated resident microglia) as liquefactive necrosis occurs (beginning 3– 5 days after the infarct), and ﬁnally proliferation of an abundance of astrocytes that marginate and form a scar (Fig. 4d) along the borders of an infarct from about 7– 10 days after ischemia and then persist for life of the patient (Fig. 5). None of these time frames are precise, particularly in aged individuals, where the process of aging, as well as the exposure to other conditions, may inﬂuence the level of reactive astrogliosis that is observed. ‘Chronic cystic infarcts’ are usually associated with astrocytic gliosis [247], and a characteristic ﬁnding in a cortical cystic infarct is the preservation of the relatively paucicellular molecular layer overlying it and located immediately beneath the meninges, which then develops a dense collection of astrocytes, usually with gemistocytic phenotype. Astrocytic processes usually traverse the cystic cavity left by the death of brain tissue, in a delicate meshwork, with persistence of foamy histiocytes among the glial ﬁbers. The role of reactive astrogliosis in the evolution of ischemic brain lesions is at present uncertain, but recent studies suggest that reactive astrocytes provide essential metabolic support to neurons during transient ischemia and Fig. 5 Reactive astrogliosis demarcates cerebral microinfarcts. Sur- vey image of cerebral cortex of an elderly individual showing microinfarcts (arrows) highlighted by dense clusters of prominently reactive astrocytes that stain intensely for GFAP. Fibrous astrocytes within subcortical white matter (wm) exhibit GFAP staining, whereas GFAP is not detectable in most protoplasmic gray matter astrocytes remote from the lesions in this specimen. H haematoxylin counter- stain. Scale bar 180 lm 19 that failure of astrocyte functions may contribute to neu- ronal degeneration [196, 237]. In addition, experimental disruption of astroglial scar formation in transgenic mice after stroke is associated with loss of barrier functions along the margins of infarcts, resulting in increased spread of inﬂammation and increased lesion volume [123]. Stroke may also induce neurogenesis from periventric- ular neural progenitor cells that express GFAP [173]. Newly ‘born’ neuroblasts and immature neurons migrate to the infract region where they associate intimately with the cerebral microvasculature in and around the infarct, which itself is undergoing intense post-stroke remodeling. It remains to be seen whether this interesting interplay of neurogenic and vascular elements will become relevant in the treatment of human strokes. Infection Reactive astrogliosis is prominent in most CNS infections. Astrocytes can be both targets of, as well as responders to, infectious agents, especially viruses. Subpial astrocytes are especially prominent in individuals who have survived an episode of purulent or granulomatous meningitis, and their appearance of reactivity depends in large part on how quickly antibiotic therapy was initiated. The roles of reactive astrocytes during the response to infection are only beginning to be elucidated. For example, reactive and scar- forming astrocytes accumulate prominently around micro- bial abscesses, and recent evidence indicates that reactive astrocytes play essential roles in restricting the spread of invading microbial agents such as Toxoplasma gondii into CNS parenchyma [59]. These observations are consistent with the putative protective barrier functions of reactive astrocytes to infectious agents and inﬂammatory cells (Fig. 4d) as discussed above and elsewhere [226]. Reactive astrogliosis can also occur in response to peripheral infections that result in circulating bacterial antigens or endotoxins, such as LPS, due to peritonitis or sepsis without direct CNS infection [105, 213]. Reactive astrocytes are prominent in different types of viral encephalitis. Astrocytes are a main target and reser- voir of human herpes virus 6 in the CNS, which can cause encephalitis in both healthy and immunsuppressed patients [57, 222]. Astrocytes are also a main target of human T-lymphotropic virus type-1, leading to disturbances in glutamate homeostasis and excitotoxicity [3, 235]. In addition to being targets of certain viruses, reactive astro- cytes may take part more generally in regulating CNS inﬂammatory responses [226]. Perivascular cufﬁng, which is a common and essentially deﬁning feature of different types of viral encephalitis, may occur as a result of barrier functions of reactive scar forming astrocytes that restrict the spread of inﬂammatory cells into CNS parenchyma 123