Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.

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Astrocytes: biology and pathology

https://www.cell.com/trends/neurosciences/pdf/S0166-2236(09)00153-2.pdf

Molecular dissection of reactive astrogliosis and glial scar formation.

[Crohn's disease].

Retinal ischemia: mechanisms of damage and potential therapeutic strategies.

Regeneration and tissue repair processes consist of a sequence of molecular and cellular events which occur after the onset of a tissue lesion in order to restore the damaged tissue. The exsudative, proliferative, and extracellular matrix remodeling phases are sequential events that occur through the integration of dynamic processes involving soluble mediators, blood cells, and parenchymal cells. Exsudative phenomena that take place after injury contribute to the development of tissue edema. The proliferative stage seeks to reduce the area of tissue injury by contracting myofibroblasts and fibroplasia. At this stage, angiogenesis and reepithelialization processes can still be observed. Endothelial cells are able to differentiate into mesenchymal components, and this difference appears to be finely orchestrated by a set of signaling proteins that have been studied in the literature. This pathway is known as Hedgehog. The purpose of this review is to describe the various cellular and molecular aspects involved in the skin healing process.

http://www.scielo.br/pdf/abd/v91n5/0365-0596-abd-91-05-0614.pdf

Wound healing - A literature review.

A rabbit eye model of neural ischaemia is described that uses an increased pressure in the anterior eye chamber to block the capillary supply to the retina. A microdialysis probe placed very close to the retinal surface was used to monitor release of amino acids during ischaemia. A large (two- to threefold) increase in the release of glutamate and O-phosphoserine (twofold), but not of six other amino acids monitored, occurred during initial ischaemia. During reperfusion after release of intraocular pressure, much larger (five- to 10-fold) increases in the release of these amino acids were observed. Parallel ischaemic retinal tissue damage was observed. This damage was prevented by keta-mine applied locally via a superfusion needle, suggesting that glutamate released during ischaemia, and particularly during reperfusion, was responsible for cell death.

Glutamate release in experimental ischaemia of the retina: an approach using microdialysis.

Wound healing is a dynamic interactive process that involves a sequence of molecular and cellular events. Recent advances in cellular and molecular biology have greatly expanded our understanding of the biological process involved in wound repair and tissue regeneration. From plasma extravasation, with coagulation and platelet aggregation, to reepithelialization and remodeling of injured tissue, the organism acts by trying to restore functionality tissue. Thus, the present study encompasses several cellular aspects involved in the wound healing process, as well as the main drugs used in treating the pathology related to wound healing complications. Economic aspects are also addressed, mainly related to chronic wounds of diabetic feet.

Cellular aspects of wound healing.

The present study investigated the biocompatibility of a biopolymer based on vegetable latex extracted from the Hevea brasiliensis rubber tree, implanted into the bony alveolar cavity after dental extraction in rats. A granule of latex (area = 0.25 +/- 0.04 mm(2)) was implanted inside the alveolus immediately after extraction of the upper right incisor, and the animals were sacrificed 7, 21 and 42 days after the procedure. The hemi-maxillas were decalcified and processed for embedding in paraffin to obtain semi-serial longitudinal sections 5 mum thick, and then stained with hematoxylin-eosin. The latex granule was observed in the cervical third of the alveolus without any foreign body reaction, or persistence of the initial acute inflammatory reaction. Bone repair in the areas adjacent to the material was quantified, and a decrease was noted in the thickness of the fibrous capsule surrounding the implants from 92.8 +/- 9.3 microm on day 7 to 9.4 +/- 1.8 microm on day 42 (ANOVA, P = 0.01). The quantitative data confirmed acceleration of bone formation (statistically significant at 5%) in parallel with a decrease of connective tissue in the areas around the implants. These results show that the tested material is biologically compatible, and progressively integrated into the alveolar bone, simultaneously accelerating bone formation and playing an important role in the healing process.

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Biocompatibility of natural latex implanted into dental alveolus of rats.

Increases in vascular permeability and angiogenesis are crucial events to wound repair, tumoral growth and revascularization of tissues submitted to ischemia. An increased vascular permeability allows a variety of cytokines and growth factors to reach the damaged tissue. Nevertheless, the angiogenesis supply tissues with a wide variety of nutrients and is also important to metabolites clearance. It has been suggested that the natural latex from Hevea brasiliensis showed wound healing properties and angiogenic activity. Thus, the purpose of this work was to characterize its angiogenic activity and its effects on vascular permeability and wound healing. The serum fraction of the latex was separated from the rubber with reduction of the pH. The activity of the dialyzed serum fraction on the vascular permeability injected in subcutaneous tissue was assayed according Mile's method. The angiogenic activity was determined using a chick embryo chorioallantoic membrane assay and its effects on the wound-healing process was determined by the rabbit ear dermal ulcer model. The serum fraction showed evident angiogenic effect and it was effective in enhancing vascular permeability. In dermal ulcers, this material significantly accelerated wound healing. Moreover, the serum fraction boiled and treated with proteases lost these activities. These results are in accordance with the enhancement of wound healing observed in clinical trials carried out with a biomembrane prepared with the same natural latex.

Increased vascular permeability, angiogenesis and wound healing induced by the serum of natural latex of the rubber tree Hevea brasiliensis

The angiogenic properties of natural rubber were evaluated in this work. We have used the chick chorioallantoic membrane assay (CAM) as a model to investigate the influence of the heating on biological activity in rubber membranes and in non rubber fraction as well. Results showed that natural rubber membranes can induce vascularization. It was observed that angiogenesis activity was maximum when membranes were heated in temperatures between 65oC and 85oC, considering a range from 55oC to 105oC. The same behavior was observed for non rubber fraction and it indicates that this serum fraction may be responsible for angiogenesis. When infrared spectroscopy was performed in the cast films of non rubber fraction samples, as a function of heating, no structural changes was observed. The results obtained shown that natural rubber latex films produced by casting induce the vessel growth in the CAM and it can be considered as a potential biomaterial.

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Joaquim Coutinho-Netto

Papers

Glutamate release in experimental ischaemia of the retina: an approach using microdialysis.

Cellular aspects of wound healing.

Biocompatibility of natural latex implanted into dental alveolus of rats.

Increased vascular permeability, angiogenesis and wound healing induced by the serum of natural latex of the rubber tree Hevea brasiliensis

Angiogenic properties of natural rubber latex biomembranes and the serum fraction of Hevea brasiliensis