Post-stroke depression exacerbates neurologic deficits and quality of life. Depression after ischemic stroke is known to some extent. However, depression after intracerebral hemorrhage (ICH) is relatively unknown. Increasing evidence shows that exposure to an enriched environment (EE) after cerebral ischemia/reperfusion injury has neuroprotective effects in animal models, but its impact after ICH is unknown. In this study, we investigated the effect of EE on long-term functional outcomes in mice subjected to collagenase-induced striatal ICH. Mice were subjected to ICH with the standard environment (SE) or ICH with EE for 6 h/day (8:00 am–2:00 pm). Depressive, anxiety-like behaviors and cognitive tests were evaluated on day 28 with the sucrose preference test, tail suspension test, forced swim test, light-dark transition experiment, morris water maze, and novel object recognition test. Exposure to EE improved neurologic function, attenuated depressive and anxiety-like behaviors, and promoted spatial learning and memory. These changes were associated with increased expression of transcription factor Nrf2 and brain-derived neurotrophic factor (BDNF) and inhibited glutaminase activity in the perihematomal tissue. However, EE did not change the above behavioral outcomes in Nrf2^−/− mice on day 28. Furthermore, exposure to EE did not increase BDNF expression compared to exposure to SE in Nrf2^−/− mice on day 28 after ICH. These findings indicate that EE improves long-term outcomes in sensorimotor, emotional, and cognitive behavior after ICH and that the underlying mechanism involves the Nrf2/BDNF/glutaminase pathway.

Background: The current diagnostic methods of microinvasive cervical cancer lesions are imaging diagnosis and pathological evaluation. Pathological evaluation is invasive and imaging approaches are of extremely low diagnostic performance. There is a paucity of effective and noninvasive imaging approaches for these extremely early cervical cancer during clinical practice. In recent years, ultrasound molecular imaging (USMI) with vascular endothelial growth factor receptor type 2 (VEGFR2) targeted microbubble (MB_VEGFR2) has been reported to improve the early diagnosis rates of breast cancer (including ductal carcinoma in situ), pancreatic cancer and hepatic micrometastases. Herein, we aimed to assess the feasibility of MB_VEGFR2-based USMI in extremely early cervical cancer detection to provide an accurate imaging modality for microinvasive cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) Stage IA1 and IA2). Results: We found MB_VEGFR2-based USMI could successfully distinguish extremely early lesions in diameter < 3 mm from surrounding normal tissues (all P < 0.05), and the sensitivity gradually decreased along with increasing tumor diameter. Moreover, normalized intensity difference (NID) values showed a good linear correlation with microvessel density (MVD) (R² = 0.75). In addition, all tumors could not be identified from surrounding muscles in subtracted ultrasound images when mice were administered MB_Con. Conclusions: Overall, MB_VEGFR2-based USMI has huge potential for clinical application for the early detection of microinvasive cervical cancer (FIGO Stage IA1 and IA2), providing the foothold for future studies on the imaging screening of this patient population.