Differential Vulnerability and Response to Injury among Brain Cell Types Comprising the Neurovascular Unit.

The neurovascular unit (NVU) includes multiple different cell types, including neurons, astrocytes, endothelial cells, and pericytes, which respond to insults on very different time or dose scales. We defined differential vulnerability among these cell types, using response to two different insults: oxygen-glucose deprivation (OGD) and thrombin-mediated cytotoxicity. We found that neurons are most vulnerable, followed by endothelial cells and astrocytes. After temporary focal cerebral ischemia in male rats, we found significantly more injured neurons, compared with astrocytes in the ischemic area, consistent with differential vulnerability in vivo. We sought to illustrate different and shared mechanisms across all cell types during response to insult. We found that gene expression profiles in response to OGD differed among the cell types, with a paucity of gene responses shared by all types. All cell types activated genes relating to autophagy, apoptosis, and necroptosis, but the specific genes differed. Astrocytes and endothelial cells also activated pathways connected to DNA repair and antiapoptosis. Taken together, the data support the concept of differential vulnerability in the NVU and suggest that different elements of the unit will evolve from salvageable to irretrievable on different time scales while residing in the same brain region and receiving the same (ischemic) blood flow. Future work will focus on the mechanisms of these differences. These data suggest future stroke therapy development should target different elements of the NVU differently.

Comparative genomics of 16 Microbacterium spp. that tolerate multiple heavy metals and antibiotics.

A total of 16 different strains of Microbacterium spp. were isolated from contaminated soil and enriched on the carcinogen, hexavalent chromium [Cr(VI)]. The majority of the isolates (11 of the 16) were able to tolerate concentrations (0.1 mM) of cobalt, cadmium, and nickel, in addition to Cr(VI) (0.5-20 mM). Interestingly, these bacteria were also able to tolerate three different antibiotics (ranges: ampicillin 0-16 µg ml-1, chloramphenicol 0-24 µg ml-1, and vancomycin 0-24 µg ml-1). To gain genetic insight into these tolerance pathways, the genomes of these isolates were assembled and annotated. The genomes of these isolates not only have some shared genes (core genome) but also have a large amount of variability. The genomes also contained an annotated Cr(VI) reductase (chrR) that could be related to Cr(VI) reduction. Further, various heavy metal tolerance (e.g., Co/Zn/Cd efflux system) and antibiotic resistance genes were identified, which provide insight into the isolates' ability to tolerate metals and antibiotics. Overall, these isolates showed a wide range of tolerances to heavy metals and antibiotics and genetic diversity, which was likely required of this population to thrive in a contaminated environment.