Human and animal studies have reported widespread reductions in cerebral blood flow associated with chronic cocaine exposures. However, the molecular and cellular mechanisms underlying cerebral blood flow reductions are not well understood. Here, by combining a multimodal imaging platform with a genetically encoded calcium indicator, we simultaneously measured the effects of acute cocaine on neuronal and astrocytic activity, tissue oxygenation, hemodynamics and vascular diameter changes in the mouse cerebral cortex. Our results showed that cocaine constricted blood vessels (measured by vessel diameter Φ changes), decreasing cerebral total blood volume (HbT) and temporally reducing tissue oxygenation. Cellular imaging showed that the mean astrocytic Ca2+ dependent fluorescence $$(\Delta {F/F}_{{{{\rm{Ca}}}^{2+}}{\mbox{-}{{{\rm{G(A)}}}}}})$$ ( Δ F / F Ca 2 + - G(A) ) increase in response to cocaine was weaker but longer lasting than the mean neuronal Ca2+ dependent fluorescence $$(\Delta {F/F}_{{{{\rm{Ca}}}^{2+}}{\mbox{-}{{{\rm{G(N)}}}}}})$$ ( Δ F / F Ca 2 + - G(N) ) changes. Interestingly, while cocaine-induced $$\Delta {F/F}_{{{{\rm{Ca}}}^{2+}}{\mbox{-}{{{\rm{G(N)}}}}}}$$ Δ F / F Ca 2 + - G(N) increase was temporally correlated with tissue oxygenation change, the $$\Delta {F/F}_{{{{\rm{Ca}}}^{2+}}{\mbox{-}{{{\rm{G(A)}}}}}}$$ Δ F / F Ca 2 + - G(A) elevation after cocaine was in temporal correspondence with the long-lasting decrease in arterial blood volumes. To determine whether the temporal association between astrocytic activation and cocaine induced vasoconstriction reflected a causal association we inhibited astrocytic Ca2+ using GFAP-DREADD(Gi). Inhibition of astrocytes attenuated the vasoconstriction resulting from cocaine, providing evidence that astrocytes play a critical role in cocaine’s vasoconstrictive effects in the brain. These results indicate that neurons and astrocytes play different roles in mediating neurovascular coupling in response to cocaine. Our findings implicate neuronal activation as the main driver of the short-lasting reduction in tissue oxygenation and astrocyte long-lasting activation as the driver of the persistent vasoconstriction with cocaine. Understanding the cellular and vascular interaction induced by cocaine will be helpful for future putative treatments to reduce cerebrovascular pathology from cocaine use.

In this study, according to the characteristics of teaching resources in higher education institutions, a university teaching resource management system is designed. The system is based on the open source SSH framework and Ajax technology. The system mainly includes 7 main functional modules. They are teaching resource library, 4 online sub-systems (courses, teaching, interactive communication and homework), intelligent auto-test/exam-generation, and student quiz/test/exam. The application of the system has been tested and the results demonstrate its feasibilities including scientific classification management, efficient retrieval, and fast sharing and downloading. The integration of SSH and AJAX based information technology into existing teaching system is very straightforward, in aspects of rich architecture, sub-system dependence, simplification of coding, and high performance of Web application development. The proposed system can be used for have broad application prospects with open sources and enterprise-level J2EE development tools.

It is estimated that there are more than two million people addicted to cocaine in the United States. How cocaine affects neuronal functions has been extensively studied. Astrocytes, an important member of the neurovascular unit, also play significant roles in brain pathology. However, their role in cocaine use disorder is unclear. Astrocytes are glial cells that support the neurons and maintain the blood‐brain barrier. Astrocytes can express inducible nitric oxide synthase (iNOS) that is responsible for the transient production of nitric oxide (NO). Both iNOS and NO have been reported to be actively involved in cocaine addiction. We hypothesize that cocaine can cause astrocyte activation and inflammation, resulting in iNOS upregulation, which can in turn, affect both neuronal and brain microvascular endothelial functions. To test this hypothesis, an in vitro astrocyte culture model and an in vivo chronic cocaine mouse model were used. In the in vitro model, human astrocytes from the cerebrocortex were treated with cocaine (10μM) (or lipopolysaccharide at 2μg/mL as the positive control) for 24 hours. iNOS expression was measured using solid‐phase ELISA. Astrocyte activation was assessed by immunofluorescence microscopy for Glial Fibrillary Acidic Protein (GFAP) expression. Changes in astrocyte morphology were quantified using a Sholl analysis. In the in vivo model, wild type C57BL/6 mice were treated with cocaine (30 mg/kg per day through intraperitoneal injection) for two weeks. Mouse brain tissue, especially in the prefrontal cortex, was collected and fixed with paraformaldehyde before slicing. Astrocyte activation and number were quantified using immunofluorescence microscopy (of GFAP). Astrocyte iNOS expression was measured using an iNOS ELISA kit (using collected mouse brain homogenate). The results demonstrated that lipopolysaccharide (LPS, the endotoxin) significantly increased iNOS expression after 24hr treatment. Cocaine, in comparison, had a more significant impact in iNOS upregulation in early passages of cultured astrocytes. Sholl analysis demonstrated that cocaine and LPS both induced significant morphological changes and reduced the number of astrocyte processes. Results obtained from the in vivo studies indicated that chronic cocaine treatment significantly decreased the number of astrocytes in the mouse prefrontal cortex, while increasing iNOS expression. In summary, astrocytes can respond to cocaine stimulation in vitro and in vivo, likely through iNOS‐medicated inflammatory responses. Therefore, investigation in the role of astrocytes in cocaine addiction may bring insight to new therapeutic target to treat cocaine use disorder.