# Sex Steroids and IGF1 in the CNS Following aSAH and Their Relationship to Patient Outcomes

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $379,867

## Abstract

PROJECT SUMMARY
 Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurologic insult that
accounts for more than 25% of stroke related deaths. Survival after aSAH is often complicated
by the development of delayed cerebral ischemia (DCI) and long term disability. Although
aneurysm repair techniques have improved, predictors of risk for poor outcomes or interventions
that substantially improve outcomes remain elusive.
 Based on evidence from the literature and our preliminary data, we believe that sex steroids
are promising biomarkers following neurological injury including aSAH, but there is a gap in
understanding their individual and collective roles in pathophysiology and outcome in humans,
specifically following aSAH. Sex steroids control local inflammation, mediate vasodilation and
are known molecular regulators of cell survival. IGF1 is a peptide hormone that exerts pro-
survival signals in virtually every cell type, including the neurons, glia, and micro-vessels of the
neurovascular unit and has been linked to estrogen mediated neuroprotection. Biomarker
concentration and bioactivity are influenced by genetic predisposition. We posit that
neuroprotective properties of sex steroids following aSAH depend on a complex balance
between sex steroids, IGF1, and genetic factors - linkages that previously have not been
investigated. The goal of this proposed project is to better determine (1) the biological
underpinnings of sex steroids and IGF1 in the central nervous system following aSAH and (2)
their relationships with patient outcomes.
 Our highly successfully research team will utilize a well characterized and longitudinally
phenotyped cohort of 536 aSAH patients with linked DNA, plasma and cerebrospinal fluid (CSF)
samples which are available from an existing aSAH biorepository to: 1) examine the relationship
between sex steroid and IGF1 concentrations during the first 14 days following aSAH to the
development of DCI and 3- and 12-month patient outcomes; 2) examine the ability of plasma to
predict CSF levels of biomarkers indicative of the brain's response to injury for patients without
CSF access; and 3) determine the ability of polymorphisms in candidate genes specific to the
sex steroid and IGF1 biosynthetic pathway to differentiate patients at risk for DCI and poor
outcomes at 3- and 12-months following aSAH. Cross-sectional and trajectory models will be
generated from daily aSAH plasma and CSF sex steroid levels (i.e., E2, E1, testosterone and
androstenedione) measured by liquid chromatography-tandem mass spectrometry and IGF1
concentrations measured by ELISA. The Custom iPLEX MassArray platform will be used to
examine candidate genes involved in the biosynthetic pathway of sex steroids and IGF1.
 Results from this proposed study will (1) lead to a better determination of the biologic
underpinnings and mechanisms for variability in patient outcomes after aSAH, (2) identify stable
genetic predictors of unfavorable outcomes (i.e. d...

## Key facts

- **NIH application ID:** 9988856
- **Project number:** 5R01NR018160-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Elizabeth A Crago
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $379,867
- **Award type:** 5
- **Project period:** 2018-09-20 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988856

## Citation

> US National Institutes of Health, RePORTER application 9988856, Sex Steroids and IGF1 in the CNS Following aSAH and Their Relationship to Patient Outcomes (5R01NR018160-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9988856. Licensed CC0.

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