# Sex Differences in Inflammation Across the Lifespan

> **NIH NIH R35** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2024 · $1,134,900

## Abstract

PROJECT SUMMARY
Stroke affects over 15 million people worldwide each year and remains the leading cause of disability in the
United States. The economic burden of stroke is increasing as the population ages, making the prevention and
treatment of vascular disease a critical public health issue. Elderly women are a third more likely to develop post-
stroke depression, have greater rates of post-stroke cognitive decline, and have poorer quality of life after stroke
compared to age-matched men. Many biological factors contribute to these disparities, including social factors,
intrinsic sex differences in cell death, and chromosomal sex. As neonates, male mice (and boys) are more
sensitive to ischemia. However, with aging, female mice (and women) have worse outcomes, in part due to loss
of estrogen with reproductive senescence. We have found that genes on the X chromosome that escape
inactivation contribute to significant sex differences in the inflammatory response, both in the brain (microglia)
and in the periphery. We have extended our work to examine sex differences in adipose tissue, in the gut (and
its microbiome), and in the cerebral vasculature. My research focuses on elucidating the fundamental
mechanisms responsible for sex and age differences in cell death, inflammatory responses, and neural repair
throughout the lifespan. The goal of my program is to translate these findings into novel, targeted therapies for
use in patients of both sexes.
Over the past 20 years, our NINDS-funded research program has pioneered work that has improved our
understanding of how sex contributes to cell death. We have a particular emphasis on cerebrovascular diseases,
and have developed programs investigating neonatal injury, vascular dementia, and stroke. Our studies have
revealed that sex differences contribute to the response to brain injury, and in the efficacy of a variety of
neuroprotective agents. The growing recognition that sex is a critical biological variable has led to changes in
NIH policy, which now mandates inclusion of females in pre-clinical studies. Sex differences have also been
identified in the clinical setting. Recognition of these factors has led to sex disaggregation of clinical trial
outcomes and an improved understanding of factors that contribute to low enrollment of women in trials. In this
application, we will consolidate three ongoing NINDS-funded proposals that focus on 1.) age-related
inflammation, 2.) the chromosomal contribution to stroke, and 3.) the detrimental effects of social isolation. We
will leverage our existing knowledge to produce new research that challenges the existing paradigm by
integrating information across these areas. Our research protocol will build on our past successes using cutting-
edge neurophysiological, immunological, and behavioral tools. Successful completion of this research will
increase our understanding of sex in other neurological disorders. My long-term goal is to maximize outcomes
for all pa...

## Key facts

- **NIH application ID:** 10834236
- **Project number:** 5R35NS132265-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Louise D. McCullough
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,134,900
- **Award type:** 5
- **Project period:** 2023-05-01 → 2031-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834236

## Citation

> US National Institutes of Health, RePORTER application 10834236, Sex Differences in Inflammation Across the Lifespan (5R35NS132265-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10834236. Licensed CC0.

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