All ETDs from UAB

Advisory Committee Chair

Jennifer S Pollock

Advisory Committee Members

David M Pollock

James F George

Lisa M Curtis

Michelle V Fanucchi

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


Globally, human studies show overwhelming associations between adverse childhood experiences and cardiovascular disease (CVD) and CVD risks throughout adult life. As early as 6 years old, there are significant associations between childhood adversity and inflammation, and those association are observed throughout adult life as well. Over a decade ago, rodent models were used to establish the importance of the immune cells in hypertension, which is the major risk factor in developing CVD. Although these associations in humans are important, they pose several limitations that can be overcome by the use of animal models to study the molecular mechanisms that are mediating CVD. This dissertation characterizes the renal immune state of the rodent model used to study early life adversity, and then begins to explore how the immune cells contribute to blood pressure elevation in response to a hypertensive stimulus. To achieve the goals in this dissertation, the maternal separation (MatSep) rodent model of early life stress (ELS) was utilized. In this model, ELS was induced by separating male pups from the dam from postnatal day (PD) 2 to PD 14, for 3 hours a day. Non-separated littermates served as controls. Renal immune responses as a result of the induced ELS were studied in adulthood at 12 weeks of age. The major findings from this study are that MatSep induces programming of the innate immune system by displaying increased renal levels of IL-1β in the distal tubules and increased TLR-4 immunopositive interstitial cells in the renal medulla. Also, MatSep kidneys display increased neutrophil activation, greater numbers of CD44 immunopositive cells, and increased number of proliferating cells in the renal medulla. When given an immune challenge with LPS, MatSep rats displayed a heightened renal cytokine and chemokine gene expression which were not observed in littermate controls. Interestingly, nitric oxide (NO) blockade with LNAME led to significantly lower blood pressure compared to control, and LNAME also protected against LNAME-induced tubular injury. In summary, characterizing the renal immune profile in this dissertation allows for future in-depth studies of immune mechanisms mediating CVD and CVD risks.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.