Daniela Uziel

Blockade of Gap Junctions In Vivo Provides Neuroprotection After Perinatal Global Ischemia

Background and Purpose— We investigated the contribution of gap junctions to brain damage and delayed neuronal death produced by oxygen-glucose deprivation (OGD). Methods— Histopathology, molecular biology, and electrophysiological and fluorescence cell death assays in slice cultures after OGD and in developing rats after intrauterine hypoxia-ischemia (HI). Results— OGD persistently increased gap junction coupling and strongly activated the apoptosis marker caspase-3 in slice cultures. The gap junction blocker carbenoxolone applied to hippocampal slice cultures before, during, or 60 minutes after OGD markedly reduced delayed neuronal death. Administration of carbenoxolone to ischemic pups immediately after intrauterine HI prevented caspase-3 activation and dramatically reduced long-term neuronal damage. Conclusions— Gap junction blockade may be a useful therapeutic tool to minimize brain damage produced by perinatal and early postnatal HI.

Cellular and molecular tunnels surrounding the forebrain commissures of human fetuses

Glial cells and extracellular matrix (ECM) molecules surround developing fiber tracts and are implicated in axonal pathfinding. These and other molecules are produced by these strategically located glial cells and have been shown to influence axonal growth across the midline in rodents. We searched for similar cellular and molecular structures surrounding the telencephalic commissures of fetal human brains. Paraffin‐embedded brain sections were immunostained for glial fibrillary acidic protein (GFAP) and vimentin (VN) to identify glial cells; for microtubule‐associated protein‐2 (MAP‐2) and neuronal nuclear protein (NeuN) to document neurons; for neurofilament (NF) to identify axons; and for chondroitin sulfate (CS), tenascin (TN), and fibronectin (FN) to show the ECM. As in rodents, three cellular clusters surrounding the corpus callosum were identified by their expression of GFAP and VN (but not MAP‐2 or NeuN) from 13 to at least 18 weeks postovulation (wpo): the glial wedge, the glia of the indusium griseum, and the midline sling. CS and TN (but not FN) were expressed pericellularly in these cell groups. The anterior commissure was surrounded by a GFAP+/VN+ glial tunnel from 12 wpo, with TN expression seen between the GFAP+ cell bodies. The fimbria showed GFAP+/VN+ cells at its lateral and medial borders from 12 wpo, with pericellular expression of CS. The fornix showed GFAP+ cells somewhat later (16 wpo). Because these structures are similar to those described for rodents, we concluded that the axon guiding mechanisms postulated for commissural formation in nonhuman mammals may also be operant in the developing human brain. J. Comp. Neurol. 483:375–382, 2005.

Axons of callosal neurons bifurcate transiently at the white matter before consolidating an interhemispheric projection

The main alternative output routes of adult cortical axons are the internal capsule and the corpus callosum. How do callosal axons choose their trajectories? We hypothesized that bifurcation followed by elimination of one branch is a developmental strategy for accomplishing this aim. Using embryonic and postnatal mice, we labelled cortical projecting neurons and quantified their axonal bifurcations in correlation with the mediolateral position of their somata. Bifurcating axons were numerous in the younger brains but declined during further development. Most bifurcating axons pertained to neurons located in the dorsolateral cortex. Moreover, callosal neurons bifurcate more often than subcortically projecting cells. We then quantified bifurcations formed by dissociated green fluorescent cells plated onto cortical slices. Cells grown over dorsolateral cortex bifurcated more often than those grown over medial cortex, irrespective of their positional origin in the donor. Removal of intermediate targets from the slices prevented bifurcation. We concluded that transient bifurcation and elimination of the lateral branch is a strategy employed by developing callosal axons in search of their targets. As cell body position and intermediate targets determine axon behaviour, we suggest that bifurcations are regulated by cues expressed in the environment.

Temporal and spatial regulation of interneuron distribution in the developing cerebral cortex—an in vitro study

GABAergic interneurons are local circuit cells that control the excitatory balance in most regions of the nervous system, particularly the cerebral cortex. Because they are integrated in every cortical module, we posed the question whether interneuronal precursors would display some topographic specificity between their origin at the ventral telencephalon and their cortical location after migration. If this was true, GABAergic cells would have to be provided with intrinsic features that would make them able to perform specific functional roles in each specific module. On the other hand, if no topography was found, one would conclude that inhibitory precursors would be functionally naive, being able to integrate anywhere in the cortex, with equal capacity of performing their functions. This issue was approached by use of organotypic cultures of wild mice embryonic slices, into which fragments of the ganglionic eminence taken from enhanced green fluorescent protein (eGFP) mice were implanted, observing the topographic location of both the implant and its destination. Despite the existence of different genetic domains in the ventricular zone of the medial ganglionic eminences (MGE), we found that cells originating in different regions spread in vitro all over the mediolateral axis of the developing cortical wall, independently of their sites of origin. Results favor the hypothesis that GABAergic precursors are functionally naive, integrating into modules irrespective of which cortical area they belong to.

Neurologic birth defects after prenatal exposure to antiepileptic drugs

Maternal epilepsy has a potential for fetal injury, either antiepileptic drug (AED)–induced or as a consequence of seizures per se. The intent of this article is to explore this relationship, discussing similar patterns of malformations seen with AEDs or different disease exposure during pregnancy, and the potential role of gap junctional intercellular communication in abnormal morphogenesis.

The role of junior enterprises in the development of human resources in biotechnology: a case report in Rio De Janeiro state

Junior Enterprises are nonprofit entities run by undergraduate students. The Junior Enterprise Antonio Paes de Carvalho (EJ-APC) was established in 2010 with the major goal of stimulate the entrepreneurial skills of students in the life sciences area by the development of biotechnological products and services. Since human resources trained in basic science at the university are poorly incorporated into the private sector, we aim to demonstrate that new technologies can be developed or new markets can be achieved by the students in order to stimulate their professional career out of the academic locus.