Astrocytes: biology and pathology

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

Endocrinologic, neurologic, and visual morbidity after treatment for craniopharyngioma

Craniopharyngiomas are locally aggressive tumors which typically are focused in the sellar and suprasellar region near a number of critical neural and vascular structures mediating endocrinologic, behavioral, and visual functions. The present study aims to summarize and compare the published literature regarding morbidity resulting from treatment of craniopharyngioma. We performed a comprehensive search of the published English language literature to identify studies publishing outcome data of patients undergoing surgery for craniopharyngioma. Comparisons of the rates of endocrine, vascular, neurological, and visual complications were performed using Pearson’s chi-squared test, and covariates of interest were fitted into a multivariate logistic regression model. In our data set, 540 patients underwent surgical resection of their tumor. 138 patients received biopsy alone followed by some form of radiotherapy. Mean overall follow-up for all patients in these studies was 54 ± 1.8 months. The overall rate of new endocrinopathy for all patients undergoing surgical resection of their mass was 37% (95% CI = 33–41). Patients receiving GTR had over 2.5 times the rate of developing at least one endocrinopathy compared to patients receiving STR alone or STR + XRT (52 vs. 19 vs. 20%, χ2P < 0.00001). On multivariate analysis, GTR conferred a significant increase in the risk of endocrinopathy compared to STR + XRT (OR = 3.45, 95% CI = 2.05–5.81, P < 0.00001), after controlling for study size and the presence of significant hypothalamic involvement. There was a statistical trend towards worse visual outcomes in patients receiving XRT after STR compared to GTR or STR alone (GTR = 3.5% vs. STR 2.1% vs. STR + XRT 6.4%, P = 0.11). Given the difficulty in obtaining class 1 data regarding the treatment of this tumor, this study can serve as an estimate of expected outcomes for these patients, and guide decision making until these data are available

Oxide enrichment by syntectonic melt-rock interaction

Processes that enrich rocks in oxides, such as ilmenite, are controversial. Current models include magmatic accumulation, crystallisation of veins from immiscible liquids and syntectonic differentiation. In this contribution, we investigate examples of oxide enrichment in both the oceanic and continental crust. The oceanic samples are of oxide gabbros (with up to 45 vol% oxides) from the Atlantis Bank oceanic core complex, Southwest Indian Ridge. The continental sample is from the Cattle Water Pass shear zone (with up to 20 vol% oxides) associated with the intracontinental Alice Springs Orogeny, central Australia. We argue for the occurrence of an open chemical system, with melt rock reactions as a key process involved in oxide enrichment in melt-fluxed shear zones. Our detailed microstructural characterisation reveals that oxides replace silicates and form interstitial grains, grain boundary films and low dihedral angles between silicates often making up an interconnected skeletal texture. Quantitative orientation data reveals that the oxides: 1) have limited internal deformation, 2) form clusters of grains that are connected in 3D, 3) have crystal faces matching the orientation of the grain boundary of nearby newly crystallised diopside (oceanic sample) and 4) form part of the foliation defining assemblage with biotite (continental sample). This evidence suggests the oxides crystallised in the presence of melt and formed during melt-rock interaction. Syntectonic melt migration is known to result in low strain microstructures in shear zones, as the strain is accommodated by the melt that existed in the deforming rock. This produces a high strain rock with silicate and oxide minerals that show limited internal deformation. Microchemical data shows major element variability in silicates and ilmenite at the thin section scale, supporting an open chemical system with local variability in both oceanic and continental settings. It further argues that syntectonic melt migration is important in oxide enrichment. Mineral chemistry data implies that the oceanic tectonic setting involved melt-rock interaction with fractionated gabbroic melt while the continental setting involved peraluminous granite melt driving mineral replacement and enrichment of oxides. We propose that deformation assisted reactive porous flow of near liquidus melt through rocks in any tectonic setting may result in melt-rock interaction induced crystallisation of oxides in preference to silicates and that with high time-integrated melt flux, the accumulation of oxides can be significant