Subfornical organ neurons integrate cardiovascular and metabolic signals

The subfornical organ (SFO) is a critical circumventricular organ involved in the control of cardiovascular and metabolic homeostasis. Despite the abundant literature clearly demonstrating the ability of SFO neurons to sense and respond to a plethora of circulating signals that influence various physiological systems, investigation of how simultaneously sensed signals interact and are integrated in the SFO is lacking. In this study, we use patch clamp techniques to investigate how the traditionally classified ‘cardiovascular’ hormone angiotensin II (ANG), ‘metabolic’ hormone cholecystokinin (CCK) and ‘metabolic’ signal glucose interact and are integrated in the SFO. Sequential bath-application of CCK (10nM) and ANG (10nM) onto dissociated SFO neurons revealed that: 63% of responsive SFO neurons depolarized to both CCK & ANG; 25% depolarized to ANG only; and 12% hyperpolarized to CCK only. We next investigated the effects of glucose by incubating and recording neurons in either hypo-, normo- or hyperglycemic conditions for a minimum of 24 hours and comparing the proportions of responses to ANG (n=55) or CCK (n=83) application in each condition. A hyperglycemic environment was associated with a larger proportion of depolarizing responses to ANG (X2, p<0.05), and a smaller proportion of depolarizing responses along with a larger proportion of hyperpolarizing responses to CCK (X2, p<0.01). These data demonstrate that SFO neurons excited by CCK are also excited by ANG, suggesting that CCK may influence fluid intake or blood pressure via the SFO, complementary to the well-understood actions of ANG at this site. Additionally, the demonstration that glucose environment affects the responsiveness of neurons to both these hormones highlights the ability of SFO neurons to integrate multiple metabolic and cardiovascular signals to affect transmission of information from the circulation to the brain, which has important implications for this structure’s critical role regulation of autonomic function.

Performance and Assessment of Rehabilitated Steel Culverts

This thesis explores the effects of rehabilitation on the structural performance of corrugated steel culverts. A full-scale laboratory experiment investigated the effects of grouted slip-liners on the performance of two buried circular corrugated steel culverts. One culvert was slip-lined and grouted using low strength grout, while the other was slip-lined and grouted using high strength grout. The performances of the culverts were measured before and after rehabilitation under service loads using single wheel pair loading at 0.45m of cover. Then, the rehabilitated culverts were loaded to their ultimate limit states. Results showed that the low and high strength grouted slip-liners provided strength well beyond requirements, with the low strength specimen failing at a load 2.4 times the fully factored service load, while the high strength specimen did not reach an ultimate limit state before bearing failure of the soil stopped testing. Results also showed that the low strength specimen behaved rigidly under service loads and flexibly under higher loads, while the high strength specimen behaved rigidly under all loads. A second full-scale experiment investigated the effect of a paved invert rehabilitation procedure on the performance of a deteriorated horizontal ellipse culvert. The performance of the culvert before and after rehabilitation was examined under service loads using tandem axle loading at 0.45m of cover. The rehabilitated culvert was then loaded up to its ultimate limit state. The culvert failed due to the formation of a plastic hinge at the West shoulder, while the paved invert cracked at the invert. Results showed that the rehabilitation increased the structural performance of the culvert, increasing the system stiffness and reducing average strains and local bending at critical locations in the culvert under service loads. A sustainability rating tool specifically for the evaluation of deteriorated culvert replacement or rehabilitation projects was also developed. A module for an existing tool, called GoldSET, was created and tested using two case studies, each comparing the replacement of a culvert using a traditional open-cut method with two trenchless rehabilitation techniques. In each case, the analyses showed that the trenchless techniques were the better alternatives in terms of sustainability.