# Cellular Mechanisms of Insulin-like Growth Factor-1 Neuroprotection with Ischemic Stroke

> **NIH NIH F31** · UNIVERSITY OF MISSISSIPPI · 2022 · $28,494

## Abstract

Project Summary
Strokes are a leading cause of mortality and disability worldwide. There is a dire need for new, effective
pharmacotherapeutics that can be administered following stroke to reduce the burden of disease and disorder
in the months after insult. The long-term goal of our laboratory is to understand how neuroendocrine modulators
can be used to treat ischemic stroke and other neurological diseases associated with advanced age. Considering
the inverse correlations between the levels of insulin-like growth factor-1 (IGF-1) and the risk and extent of
damage with ischemic stroke in humans, our current goal is to understand the cellular mechanisms that mediate
the protective effects of IGF-1. Following a stroke, the core and penumbral regions undergo drastic changes that
lead to imbalances in ions, pH, as well as increased levels of extracellular glutamate. These changes instigate
an expansion of neuronal death whereby secondary increases in reactive oxygen species, inflammatory cytokine
production, and mitochondrial dysfunction in surrounding cells precipitates further damage in the days and weeks
following initial insult. Importantly, administration of exogenous IGF-1 to rodent models of ischemia attenuates
infarct size, neurological damage, and the functional deficits in commonly seen in spatial learning and memory
and sensorimotor function. Evidence from our laboratory has shown that reductions of the IGF-1 receptor (IGF-
1R) in astrocytes reduces their ability to buffer excitotoxic levels of glutamate. Based on this, we proposed that
loss of astrocytic IGF-1 signaling could increase the extent of stroke damage. On the other hand, exogenous
IGF-1 has also been shown to directly protect neurons from stroke-like insults in vitro, and the extent of protection
is significantly influenced by the presence of astrocytes. Thus, it is likely that IGF-1 protects neurons by directly
modulating the neurons themselves and/or indirectly, by modulating astrocytes. Our hypothesis is that the
functional regulation of both neurons and astrocytes by IGF-1 is critical to minimize damage in ischemic
stroke. To address this, we will utilize our novel transgenic mouse models of inducible astrocyte-specific or
neuron-specific Cre recombinase to reduce IGF-1R in specific cell populations in the adult brain. These mice will
be subjected to ischemic stroke via middle cerebral artery occlusion and we will subsequently analyze the extent
of tissue damage, sensorimotor dysfunction, as well as cellular and molecular changes within the surviving
tissue. Special emphasis is placed on examining changes in glutamate handling, astrocytic activation and
relocation, and key astrocyte functions. These experiments will determine whether astrocytes and/or neurons
IGF-1 signaling is necessary and sufficient for the beneficial effects of IGF-1 on attenuating tissue and
neurological damage in the time surrounding ischemic stroke. Conclusions from this project will underscore the
...

## Key facts

- **NIH application ID:** 10466243
- **Project number:** 1F31NS124302-01A1
- **Recipient organization:** UNIVERSITY OF MISSISSIPPI
- **Principal Investigator:** Cellas Hayes
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $28,494
- **Award type:** 1
- **Project period:** 2022-04-13 → 2022-12-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10466243

## Citation

> US National Institutes of Health, RePORTER application 10466243, Cellular Mechanisms of Insulin-like Growth Factor-1 Neuroprotection with Ischemic Stroke (1F31NS124302-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10466243. Licensed CC0.

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