Astrocyte responses to injury: VEGF simultaneously modulates cell death and proliferation

Hypoxia is linked to changes in blood brain barrier (BBB) permeability and loss of BBB integrity is characteristic of many pathological brain diseases including stroke. In particular astrocytes play a central role in brain homeostasis and BBB function. We investigated how hypoxia affects astrocyte survival and assessed whether VEGF release through Hif-1alpha induction plays a role in the tolerance of these cells to insult. Thus primary astrocytes were subjected to normoxic (21% O2), hypoxic (1% O2) or near anoxic (<0.1% O2) conditions in presence or absence of glucose. Cell death was significantly initiated after combined oxygen glucose deprivation and surprisingly, astrocyte proliferation increased concomitantly. Near anoxic, but not hypoxic, conditions stabilised HIF-1alpha protein and provoked DNA binding activity whereas oxygen and glucose deprivation accelerated HIF-1alpha accumulation. Unexpectedly HIF-1alpha knockdown studies showed that elevated VEGF levels following increased insult was only partially due to HIF-1alpha induction suggesting alternative mechanisms of VEGF regulation. Notably, endogenous VEGF signalling during insult was essential for cell fate since VEGF inhibition appreciably augmented cell death and reduced proliferation. These data suggest Hif-1 only partially contributes to the VEGF-mediated astrocyte responses during chronic injury (as occurs in clinical hypoxic/ischemic insults) that may ultimately be responsible for disrupting BBB integrity. Key words: oxygen deprivation, blood brain barrier, glucose deprivation, permeability, glial scarring

Liposarcoma in a veiled chameleon (Chamaeleo calyptratus)

A three year-old male veiled chameleon (Chamaeleo calyptratus) with clinical signs of anorexia and distended coelom was evaluated. Radiographs and ultrasonography revealed coelomic and pericardial effusion. Coelomocentesis and pericardiocentesis yielded a modified transudate. Based on the poor response to symptomatic therapy with a poor prognosis the chameleon was euthanized. The histopathological examination of lung, liver, heart and kidney tissue revealed proliferation of poorly differentiated cells with pleomorphic nuclei and abundant, finely vacuolated cytoplasm, a typical feature of liposarcoma. This is the first diagnosis of a liposarcoma with metastasis in several organs of a veiled chameleon

Serum iron metabolites in an opportunistic sample of different captive primate species

Previous reports in the literature indicate that primate species differ in their iron metabolism. Analyses were carried out of 229 serum samples of 18 different species, including marmosets, lemurs, woolly monkeys, colobines, macaques, baboon and great apes, for transferrin saturation (%TS), an indicator of iron absorption. In correspondence with our expectations based on the literature, lemurs and marmosets had significantly higher %TS values than great apes and macaques/baboon. The findings corroborate patterns previously described in individual studies, and underline that further efforts should be made to understand the reasons and consequences of these differences in iron metabolism

Live-fibroblast IR imaging of a cytoprotective PhotoCORM Activated with Visible Light

Carbon monoxide releasing molecules (CORMs) are an emerging class of pharmaceutical compounds currently evaluated in several preclinical disease models. There is general consensus that the therapeutic effects elicited by the molecules may be directly ascribed to the biological function of the released CO. It remains unclear, however, if cellular internalization of CORMs is a critical event in their therapeutic action. To address the problem of cellular delivery, we have devised a general strategy which entails conjugation of a CO-releasing molecule (here a photoactivated CORM) to the 5'-OH ribose group of vitamin B12. Cyanocobalamin (B12) functions as the biocompatible water-soluble scaffold which actively transports the CORM against a concentration gradient into the cells. The uptake and cellular distribution of this B12-photoCORM conjugate is demonstrated via synchrotron FTIR spectromicroscopy measurements on living cells. Intracellular photoinduced CO release prevents fibroblasts from dying under conditions of hypoxia and metabolic depletion, conditions that may occur in vivo during insufficient blood supply to oxygen-sensitive tissues such as the heart or brain