Nrf2 is a key transcriptional factor for antioxidant response element (ARE)-regulated genes. While its beneficial role has been described for stroke, its contribution to intracerebral hemorrhage (ICH)-induced early brain injury remains to be determined. Using wildtype (WT) and Nrf2 knockout (Nrf2 −/− ) mice, the role of Nrf2 in ICH induced by intracerebral injection of collagenase was investigated. The results showed that injury volume was significantly larger in Nrf2 −/− mice than in WT controls 24 h after induction of ICH (p < 0.05), an outcome that correlated with neurological deficits. This exacerbation of brain injury in Nrf2 −/− mice was also associated with an increase in leukocyte infiltration, production of reactive oxygen species, DNA damage, and cytochrome c release during the critical early phase of the post-ICH period. In combination, these results suggest that Nrf2 reduces ICH-induced early brain injury, possibly by providing protection against leukocyte-mediated free radical oxidative damage.

Stroke and Alzheimer’s disease (AD) are major age-related neurodegenerative diseases that may worsen the prognosis of each other. Our study was designed to delineate the prostaglandin E2 EP1 receptor role in AD and in the setting of cerebral ischemia. Genetic deletion of the prostaglandin EP1 receptor significantly attenuated the more severe neuronal damage (38.5 ± 10.6%) and memory loss induced by ischemic insult that observed in AD transgenic mice (percentage of viable hippocampal CA1 neurons: 11.2 ± 2.9%) when compared to wildtype mice (45.1 ± 9.1%). In addition, we found that the amyloid plaques were reduced in EP1 deleted AD mice. Aβ-induced toxicity (18.0 ± 7.1%) and Ca2+ response (91.8 ± 12.9%) were also reduced in EP1−/− neurons compared to control neurons in in vitro. Hence, EP1 might mediate most of the toxicity associated with COX-2 and contribute substantially to the cell death pathways in AD and stroke. Exploring potential therapeutic agent targeting EP1 receptor could potentially benefit treatments for stroke and AD patients.

After pneumonectomy, the remaining lung increases in size. This process is referred to as compensatory lung growth. Various pathways likely play important roles in this growth response. The molecular mechanisms involved in compensatory lung growth, however, remain poorly understood. Hypoxia-induced mitogenic factor (HIMF), also called FIZZ1 or RELM-alpha, possesses mitogenic, vasoconstrictive, angiogenic, and antiapoptotic effects. In this study, we examined the expression of HIMF in mouse lung after pneumonectomy to test the hypothesis that HIMF expression is upregulated during compensatory lung growth. Results showed that HIMF is upregulated from Day 1 after pneumonectomy and peaking at Day 7 in the lung. HIMF upregulation is temporally and spatially related to lung cell proliferation, as demonstrated by expression of proliferating cell nuclear antigen. Immunohistochemical staining and in situ hybridization showed that upregulated HIMF protein and mRNA are mainly distributed in airway epithelium, alveolar type II cells, and endothelial cells of the pulmonary vessels. Intratracheal instillation of recombinant HIMF resulted in widespread cell proliferation, including airway epithelium, alveolar type II cells, and cells in the alveolar septa. These results indicate a new role for HIMF in compensatory lung growth, which is that HIMF may act as a lung-specific growth factor and participate in lung regeneration after pneumonectomy.

The objective of the present investigation was to examine the residual antimicrobial activity after a topical exposure of reconstructed human epidermis (RHE) to equimolar solutions of either chlorhexidine digluconate (CHG, 0.144% w/v) or octenidine dihydrochloride (OCT, 0.1% w/v) for 15 min. RHE-associated antiseptic agents were more effective on Staphylococcus aureus than on Pseudomonas aeruginosa. S. aureus was not detected after 24 h of contact, which demonstrated a microbicidal efficacy of greater than 5-log₁₀ reduction. In contrast, P. aeruginosa was reduced by approximately 2 log₁₀ at the same incubation time, which parallels the growth of the initial inoculum. This result could be interpreted either as a microbiostatic effect or as an adherence of P. aeruginosa to a low positively charged surface. Small amounts of CHG and OCT can penetrate the stratum corneum. Using these antiseptic agents, the viability of keratinocytes was reduced to 65-75% of that of the untreated RHE control following 24 h incubation in the presence of test microorganisms. With consideration of antimicrobial activity and cytotoxic effect, OCT corresponds better to a biocompatible antiseptic agent than CHG.