# Chronic Inflammation and Depression after Spinal Cord Injury

> **NIH NIH F30** · DREXEL UNIVERSITY · 2020 · $41,097

## Abstract

Abstract
Major depressive disorder in individuals with spinal cord injury has a profound impact on quality
of life, correlating with limited functional improvement during rehabilitation and increased
mortality rates. The incidence of depression in these individuals is three times higher than the
general population, while response rates to classical antidepressants are much lower. The
underlying physiological mechanisms responsible for SCI-induced depression are not known;
however, levels of pro-inflammatory cytokines, such as Interleukin (IL)-6 and TNFα, are often
elevated in the serum of patients with major depression. In the case of SCI, there is evidence of
remote, chronic inflammation in supraspinal brain regions that are associated with emotional
regulation, such as the dorsal raphe nucleus. As the primary source of serotonergic input to the
brain, perturbations of the dorsal raphe could result in an imbalance in serotonin- the
neurotransmitter classically associated with depression. Activity of serotonin neurons is normally
modulated through both local binding of serotonin autoreceptors on the soma and dendrites, as
well as glutamatergic projections from the prefrontal cortex to local GABAergic interneurons in
the dorsal raphe. The neural circuitry of the dorsal raphe could provide a potential source of
vulnerability to inflammation through a disruption in glutamate homeostasis. Preliminary data
from our lab indicate a significant correlation of increased levels of TNFα in the dorsal raphe
with depressive behaviors after moderate thoracic spinal cord contusion. This cytokine has been
shown to decrease expression of the glutamate transporter GLT1, significantly impairing
glutamate reuptake. Increased extracellular glutamate could result in hyperactivity of the
GABAergic interneurons, decreasing serotonin activity. We hypothesize that SCI-induced
depression is mediated by hypoactivity of serotonin neurons in the dorsal raphe, resulting from
TNFα-mediated glutamate imbalance. We will use a moderate, midline thoracic contusion model
in adult female rats to test our hypothesis. Depressive phenotype will be assessed using a
battery of behavioral tests that mimic classic symptoms of depression in patients. We believe
this depressive phenotype can be ameliorated through the inhibition of TNFα after injury and will
test for efficacy after acute or delayed treatment with XPro 1595.This study will provide us with
greater insight into the mechanism of SCI-induced depression, as well as a potential for novel
therapeutic treatment.

## Key facts

- **NIH application ID:** 9967153
- **Project number:** 5F30NS101873-04
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Kaitlin Farrell
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $41,097
- **Award type:** 5
- **Project period:** 2017-07-12 → 2021-05-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9967153

## Citation

> US National Institutes of Health, RePORTER application 9967153, Chronic Inflammation and Depression after Spinal Cord Injury (5F30NS101873-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9967153. Licensed CC0.

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