Harnessing microglia to improve neurological recovery
Funded in: 2019, 2020, 2021
Back to overview
Problem: How microglia protect neurons after SCI and promote tissue repair is unknown
Target: Microglia govern unique gene signatures and cell-cell interactions
Goal: Novel strategy to preserve neuronal integrity and promote recovery
Spinal neurons and their connections are surrounded by small cells called microglia, which continuously support neuronal integrity and function, and remove any infectious material or abnormal cells. Traumatic spinal cord injury (SCI) causes robust activation of microglia around the lesion zone. This microglial response is thought to promote spontaneous recovery of function, because elimination of microglia causes the lesion to expand into neighbouring, intact spinal tissue and worsen neurological outcomes.
However, exactly how microglia protect neurons after SCI and promote tissue repair is unknown. The research group hypothesize that microglia govern unique gene signatures and cell-cell interactions that drive spontaneous recovery, which can be boosted therapeutically to further augment recovery. This project will use genetically modified mice and gene sequencing technology to identify microglia and sequence the genes of spinal cells over time in a clinically relevant mouse model of spinal cord injury.
The researchers will compare the gene profiles of spinal cells from mice that have microglia, and mice that have no microglia. They will also boost microglia function by administering a known microglia activator (lipopolysaccharide) after SCI. These studies will reveal how microglia change their gene signatures to control lesion pathology, and how microglia can be harnessed to increase repair and recovery. Selective enhancement of specific microglial activities may be a novel strategy to preserve neuronal integrity and promote recovery of sensory and motor function after spinal trauma.