The Reactive Astrocyte

Nathaniel, E.J.H.; Nathaniel, Doris R.

doi:10.1016/b978-0-12-008302-2.50012-2

Cited by 120 publications

(50 citation statements)

References 143 publications

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“…Astrocytic proliferation is an integral component of the brain's response to injury (7,24). Since activation of EGF/ TGF-a receptors stimulates glial cell proliferation (25) and TGF-a gene expression is increased by TGF-a itself (26), TGF-a may stimulate glial cell proliferation and its own expression in reactive astrocytes via an autocrine mechanism similar to that observed in other TGF-a-producing cells (26).…”

Section: Discussionmentioning

confidence: 99%

Transforming growth factor alpha contributes to the mechanism by which hypothalamic injury induces precocious puberty.

Junier

Jin

Costa

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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It has long been known that lesions of the hypothalamus lead to female sexual precocity. While an increased production of luteinizing hormone-releasing hormone (LHRH), the neurohormone that controls sexual development, appears to mediate the advancement of puberty induced by these lesions, little is known about the mechanism(s) by which hypothalamic injury activates LHRH secretion. Since brain lesions result in accumulation of neurotrophic/mitogenic activities in the injured area, we tested the hypothesis that transforming growth factor a (TGF-a), a mitogenic polypeptide recently shown to stimulate LHRH release, is produced in response to hypothalamic injury and mediates the effect of the lesion on puberty. Radiofrequency lesions of the preoptic area-anterior hypothalamic area (POA-AHA) of 22-day-old female rats resulted in precocious puberty within 7 days after the operation. RNA blot hybridization revealed that lesioninduced puberty was preceded by an increase in TGF-a mRNA levels in the POA-AHA. Epidermal growth factor (EGF) mRNA was undetectable in both intact and lesioned hypothalami. TGF-a mRNA levels, quantitated by RNase protection assays, were 3.5-fold greater in lesioned animals approaching puberty than in age-matched controls. Immunohistochemical studies, utilizing single-and double-staining procedures, demonstrated the presence of TGF-a precursor-like immunoreactivity in reactive astrocytes surrounding the lesion site. Hybridization histochemistry showed increased TGF-a mRNA expression in cells of the same area, further implicating reactive astrocytes as a site of TGF-a synthesis. The onset of mammalian puberty depends on the activation of neurons that are located in the diencephalon and secrete the neurohormone luteinizing hormone-releasing hormone (LHRH) (for review, see ref. 1). Although most cases of precocious puberty of cerebral origin occur in girls and are diagnosed as idiopathic (2), computed axial tomography has revealed that an increasing number of these cases are associated with discrete hypothalamic pathology (2, 3). Experimentally, female sexual precocity can be induced in both primates and rodents by lesions of the hypothalamus (4, 5).Lesions of the anterior hypothalamus in rodents (5) result in true sexual precocity, as animals bearing these lesions mate and rear litters normally (6). The mechanisms underlying this phenomenon are unknown, but the notion that lesions accelerate sexual development by eliminating a site(s) for steroid inhibitory control (5) has gained acceptance. To date, an involvement of neurotrophic/mitogenic activities produced locally in response to brain injury (7) has not been considered in lesion-induced precocious puberty. We have taken advantage of this unique model (5, 6) to test the hypothesis that neurotrophic/mitogenic factors, thought to be involved in the reorganization of the brain that follows injury (7), are responsible for the advancement ofpuberty caused by hypothalamic lesions. We focused our attention on transforming growth factor a (TGF-a)...

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Section: Discussionmentioning

confidence: 99%

Transforming growth factor alpha contributes to the mechanism by which hypothalamic injury induces precocious puberty.

Junier

Jin

Costa

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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“…This can be correlated with the results obtained by GFAP immunohistochemistry, which shows swollen, reactive astrocytes, and underlines the glial nature of the late MRI signal in the cortex. The common reaction of astrocytes to injury in central nervous system is the striking hypertrophy and occasional proliferation of these cells (44)(45)(46)(47). The hypertrophy involves an increase in the size of the soma as well as an increase in the length and width of astrocytic stellae, with a hallmark accumulation of intermediate filaments such as GFAP and an increase of free water.…”

Section: Key Role Of the Cerebral Cortex In Epileptogenesismentioning

confidence: 99%

Magnetic Resonance Imaging in the Study of the Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Adult Rats

et al. 2002

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Summary:Purpose: In temporal lobe epilepsy, it remains to be clarified whether hippocampal sclerosis is the cause or the consequence of epilepsy. We studied the temporal evolution of the lesions in the lithium-pilocarpine model of epilepsy in the rat with magnetic resonance imaging (MRI) to determine the progressive morphologic changes occurring before the appearance of chronic epilepsy.Methods: MRI was performed on an MR scanner operating at 4.7 T. We followed the evolution of lesions using T 2 -and T 1 -weighted sequences before and after the injection of gadolinium from 2 h to 9 weeks.Results: At 2 h after status epilepticus (SE), a blood-brain barrier breakdown could be observed only in the thalamus; it had disappeared by 6 h. At 24 h after SE, edema was present in the amygdala and the piriform and entorhinal cortices together with extensive neuronal loss; it disappeared progressively over a 5-day period. During the chronic phase, a cortical signal reappeared in all animals; this signal corresponded to gliosis, which appeared on glial fibrillary acidic protein (GFAP) immunohistochemically stained sections as hypertrophic astrocytes with thickened processes. In the hippocampus, the correlation between histopathology and T 2 -weighted signal underscored the progressive constitution of atrophy and sclerosis, starting 2 days after SE.Conclusions: These data show the reactivity of the cortex that characterizes the initial step leading to the development of epilepsy and the late gliosis that could result from the spontaneous seizures. Moreover, it appears that hippocampal sclerosis progressively worsened and could be both the cause and the consequence of epileptic activity.

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“…We further addressed whether the mitogenic action _ _ (5) of IFN on human adult astrocytes was by a direct effect or indirect mechanism. The latter would be that IFN was stimulating microglia cells, also present in culture, to release (5) IL-1 or other cytokines mitogenic for human adult astrocytes.…”

mentioning

confidence: 99%

Gamma-interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo.

Yong

Moumdjian

Yong

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

198

127

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Reactive gliosis is a characteristic response of astrocytes to inflammation and trauma of the central nervous system. To investigate whether soluble factors (cytokines) from inflammatory mononuclear cells that accumulate at lesion sites can provide the cellular signals to initiate gliosis and to identify such cytokines, we have tested and found that supernatants derived from subsets of activated human T lymphocytes (CD8' or CD41) are potent mitogens for cultured human adult astrocytes. This effect is blocked by a neutralizing antibody to -interferon (IFN). Recombinant A consideration in relating relevance of in vitro proliferation results to reactive gliosis in vivo is that gliotic scars seldom develop after insults to the embryonic brain (22-24) but are common features in adult brain injuries. Thus, it becomes important to assess proliferation of astrocytes derived from adult animals, rather than from neonatal ones. We have adopted such a strategy by using adult human astrocytes isolated from surgical brain biopsies and have addressed the following questions. Do activated human T lymphocytes produce sufficient cytokines to induce proliferation of cultured adult human astrocytes; if so, which cytokine (s) (see Results), were treated with trysin and seeded on poly(L-lysine)-coated (10 jag/ml) 9-mm Aclar fluorocarbon coverslips at 10,000 cells per coverslip. These mixed cells were used for the present study; methods for eliminating microglia from rodent glia cultures (leucine methyl ester and silica ingestion) (28-30) were not effective for human preparations. Culture medium was Eagle's minimum essential medium supplemented with 5% (vol/vol) fetal calf serum, Gentamicin (20 gg/ml), and dextrose (1 mg/ml) (all from GIBCO).

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The Reactive Astrocyte

Cited by 120 publications

References 143 publications

Transforming growth factor alpha contributes to the mechanism by which hypothalamic injury induces precocious puberty.

Transforming growth factor alpha contributes to the mechanism by which hypothalamic injury induces precocious puberty.

Magnetic Resonance Imaging in the Study of the Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Adult Rats

Gamma-interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo.

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