# Research 3- Morton

> **NIH NIH P20** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2022 · $230,004

## Abstract

Project Summary 
This project addresses fundamental mechanisms that may contribute to the acute symptoms of concussion and 
related mild traumatic brain injuries. Our long-term goal is to increase understanding of mechanisms underlying 
acute neurological dysfunction, so that diagnosis and/or treatment can be substantially improved. This work is 
expected to be significant for the large number of individuals who suffer from concussions, including the 
substantial number who do not recover fully after single or repetitive hits. The project focuses on the 
phenomenon of Spreading Depolarization (SD), which has emerged relatively recently as a key contributor to 
lesion progression in patients in the ICU with severe traumatic brain injury or stroke. There is very limited 
knowledge about whether SDs occur in other neurological conditions. In 2018 we presented the first evidence 
that SDs occur in a murine concussion model, and another group provided a first publication with indirect 
measurements of SD in a similar model. The challenge now is to provide additional direct electrophysiological 
recordings of SD, combined with simulatenous measures of behavior, to determine whether concussion-induced 
SDs are responsible for the well-known acute symptoms of concussion. If SDs are necessary and sufficient to 
explain the symptoms, then interventions targeting SD could be very valuable for these patients, and the 
discovery could suggest new opportunities for early diagnosis. Furthermore, the large disruptions in neuronal 
and vascular function caused by SD could contribute to a window of vulnerability to second hits – a possibility 
that has not previously been investigated. This project therefore addresses key gaps in knowledge about 
mechanisms linking SD to concussion symptoms and vulnerability. We will use a mouse concussion model and 
combinations of electrophysiological and behavioral recordings, together with high-throughput anatomical 
analyses to assess for signs of neuronal injury. Specific Aim 1 tests whether the short term depression of 
synaptic activity that follows SD underlies post-concussion behaviors. Specific Aim 2 tests whether the massive 
disruptions in blood flow and/or synaptic activity that follow SD render the brain more vulnerable to a second hit 
during this acute phase. Successful completion of these aims is expected to identify SD as a significant 
contributor to the symptoms and consequences of concussion, and open new doors to detection and treatment 
of this very common and often severely debilitating type of brain injury. The project is very well suited to the 
interdisciplinary environment of the COBRE Center. Extensive input from both preclinical and clinical mentors 
and colleagues, and excellent core facilities will provide an outstanding platform for multiple high-impact 
publications and progression to independent extramural funding success.

## Key facts

- **NIH application ID:** 10468698
- **Project number:** 5P20GM109089-08
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Russell Morton
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $230,004
- **Award type:** 5
- **Project period:** 2015-09-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468698

## Citation

> US National Institutes of Health, RePORTER application 10468698, Research 3- Morton (5P20GM109089-08). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10468698. Licensed CC0.

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