Neutrophils block permeability increases induced by oxygen glucose deprivation in a culture model of the human blood-brain barrier.

Experimentally, oxygen glucose deprivation (OGD) has been widely used to mimic the environmental conditions present during cerebral ischemia-reperfusion (IR) injury. OGD is known to increase permeability across cultured cerebral endothelial cells, which models the effect of IR on permeability across the blood-brain barrier (BBB); however, studies have yet to be performed in a human model. The effect of neutrophils on the increase in BBB permeability associated with IR injury has yet to be modeled in vitro. To address these questions, the human brain endothelial cell line hCMEC/D3 was exposed to OGD with reoxygenation, and permeability was measured for a range of OGD exposure times (1-24h). One hour of exposure to OGD induced a reversible increase in permeability, unassociated with cytotoxicity (assessed from lactate dehydrogenase release). However, 12-24h OGD exposures induced sustained increases in permeability associated with cytotoxicity. The 1h permeability increase was inhibited with the nitric oxide synthase inhibitors l-NAME (10(-)(7)mol/l) and 1400W (10(-)(7)mol/l). Neutrophils (5x10(6)/ml) blocked the permeability increase associated with 1h OGD, whether applied during or after OGD exposure. Permeability remained low if neutrophils were activated with leukotriene (Lt)B(4) (10(-)(7)mol/l) or exposed to a transendothelial gradient of LtB(4), while neutrophil activation with phorbyl myristate acetate (4x10(-)(8)mol/l) induced a small increase. Neutrophils had no effect on the permeability increase induced by 12h OGD exposure. This study finds that OGD induces reversible increases in permeability linked to nitric oxide synthesis in a human culture model of the BBB and shows that neutrophils mitigate permeability increases in this context.

Splenic mass of masked shrews, Sorex cinereus, in relation to body mass, sex, age, day of the year, and bladder nematode, Liniscus (=Capillaria) maseri, infection.

The spleen is an important organ of vertebrates. Splenic mass can change in response to a variety of factors. We tested whether splenic mass of masked shrews, Sorex cinereus, was related to sex, age, time of the year, or intensity of bladder nematode (Liniscus [=Capillaria] maseri) infection, after controlling for host body mass. For females, body mass was a strong predictor of splenic mass. For males, splenic masses were greater later in the year and in more heavily infected males. The latter appeared to represent a threshold response wherein only the most heavily infected individuals had enlarged spleens.