# Investigating mitochondrial dynamics in cerebral ischemia/reperfusion injury using novel morphological analyses and computational modeling

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $38,394

## Abstract

PROJECT SUMMARY
Cerebral ischemia/reperfusion (I/R) injury, mainly caused by cardiac arrest and stroke, induces debilitative
neurological damage. A key component of cerebral I/R injury is dysfunction in mitochondrial metabolism and
maintenance. The mitochondrial network is maintained by two balancing forces: fission and fusion. Under basal
conditions, these dynamic processes work to stabilize the mitochondrial network and maintain efficient energy
production. However, the processes of mitochondrial dynamics and quality control are severely disrupted by
cerebral I/R injury. The objective of the present research proposal is to identify the phases of disrupted
mitochondrial dynamics and the related molecular mechanisms in cerebral I/R injury with strict temporal
resolution. Rather than using the traditional subjective and qualitative methodologies, mitochondrial dynamics
will be probed using novel computational and quantitative tools. Utilizing advances in computational science and
artificial intelligence, a semi-automated machine learning-based classification pipeline will be constructed for the
analysis of mitochondrial morphology, the product of mitochondrial dynamics. The classification model will be
developed and validated using conditional knockout models of known molecular players in mitochondrial
dynamics (e.g. Opa1, Drp1). Additionally, an agent-based computational model of single cell mitochondrial
dynamics will be constructed and optimized using live cell imaging from primary neurons and novel genetic
reporters (e.g. MitoTimer). This computational model will be used to test hypotheses regarding the basal and
pathological rates of mitochondrial dynamics and quality control operations, as well as, inform future experiments
as a method of reducing the required number of experimental groups, timepoints, and animals. Utilizing the
newly developed and validated computational tools, live cell imaging will be performed in an in vitro model of
cerebral I/R, oxygen glucose deprivation and reoxygenation (OGD/R). Tracking mitochondrial morphology over
time during OGD/R will allow for the identification of distinct phases of mitochondrial dynamics in cerebral I/R
injury. Additionally, the specific mechanisms involved with the identified phases will be probed using conditional
knockout of key dynamics proteins. The above-mentioned procedures will further be scaled to 3D analysis of
mitochondrial morphology in the middle cerebral artery occlusion (MCAO) model of focal ischemic stroke. This
move to in vivo experimentation will provide knowledge of dynamics in a larger biological system and allow for
future translational work regarding cerebral I/R injury. This research, along with advanced academic study and
strong scientific mentorship, provide a tremendous amount of opportunities for growth and professional
development. The proposed work is uniquely positioned at the intersection of computer science, mathematics,
and neurobiology, and thus creates a re...

## Key facts

- **NIH application ID:** 10314377
- **Project number:** 1F31NS124280-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Garrett McGuire Fogo
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,394
- **Award type:** 1
- **Project period:** 2021-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10314377

## Citation

> US National Institutes of Health, RePORTER application 10314377, Investigating mitochondrial dynamics in cerebral ischemia/reperfusion injury using novel morphological analyses and computational modeling (1F31NS124280-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10314377. Licensed CC0.

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