Grant: Operating Grant: SickKids-CIHR-IHDCYH New Investigator Grants

University of Calgary

$0.00

Repetitive, mild traumatic braininjuries during adolescence altermicroglia-dependent synapticpruning

FY 2020-21

Summary

Adolescents are a key demographic that acquire mild traumatic brain injuries (mTBIs), like concussions,of which sports-related collisions are a major cause. Not surprisingly, adolescent are highly prone torepetitive injuries (RmTBIs). Over the past decade TBI-centered research has formed a convincing linkbetween the number and frequency of RmTBIs and acquisition of lingering or chronic post-injuryneurological symptoms that negatively impact motor control, cognition and emotional states. In somecases, RmTBIs even promote neurodegenerative diseases like chronic traumatic encephalopathy,Alzheimer’s disease and Parkinson’s disease. Currently there are no effective treatment therapies toslow or prevent the negative neurological consequences accompanying RmTBIs. Moreover, researchinto RmTBI pathophysiology has largely focused on adult injuries in males, limiting our understanding ofthe pathophysiological mechanisms of injury in the adolescent and female populations. This isimportant because males and females often report differential neurological symptoms and recoverytimeframes following mTBIs. Adolescent brain development is largely influenced by novel experienceswhich refine neurotransmission and neuronal circuit connectivity. Microglia are centrally important inthese processes through their phagocytic capacity to engulf, or prune, weak/unneeded synapses. Thesecells also adopt activated inflammatory phenotypes in response to brain injury, which could detract fromtheir neurodevelopmental functions. Our pilot data highlights interesting new data suggesting thatmicroglia density decreases following adolescent RmTBIs. This project aims to determine thespatiotemporal nature and cause of this phenomenon, and the resulting impact on neurodevelopmentalsynaptic pruning. Collectively, the outlined experiments in our project will produce new mechanisticinformation detailing the sex- and age-dependent effects of repetitive head injuries on glial cells andhighlight a potential new avenue for targeted interventions to decrease the socioeconomic burden ofRmTBIs in the Canadian and world populations.

Department

Canadian Institutes of Health Research

Program

Operating Grant: SickKids-CIHR-IHDCYH New Investigator Grants

Recipient

University of Calgary

Location

Alberta, Canada

Recipient Type

Academia

Type

Grant

Source

CIHR Funding Decisions Database

As published

438807

Name

Lohman Alexander W

Region

Alberta

Country

Canada

Orgtype

Institution Paid; Research Institution

Partnername

Hospital for Sick Children Foundation

Prcname2

Special Cases

Projecttitle

Repetitive, mild traumatic braininjuries during adolescence altermicroglia-dependent synapticpruning

Programtype2

Operating Grants

Orgnameinp2

University of Calgary

Cihramount2

Cihrequipment2

Programname2

Operating Grant: SickKids-CIHR-IHDCYH New Investigator Grants

Keyworddelim

Competitiondate

202007

Approvedterm2

3 yrs 0 mth

Pinamesdelim

Lohman, Alexander W

Approvedterm

3 ans 0 mois

Abstract

<html> <head> </head> <body> Adolescents are a key demographic that acquire mild traumatic brain injuries (mTBIs), like concussions,of which sports-related collisions are a major cause. Not surprisingly, adolescent are highly prone torepetitive injuries (RmTBIs). Over the past decade TBI-centered research has formed a convincing linkbetween the number and frequency of RmTBIs and acquisition of lingering or chronic post-injuryneurological symptoms that negatively impact motor control, cognition and emotional states. In somecases, RmTBIs even promote neurodegenerative diseases like chronic traumatic encephalopathy,Alzheimer’s disease and Parkinson’s disease. Currently there are no effective treatment therapies toslow or prevent the negative neurological consequences accompanying RmTBIs. Moreover, researchinto RmTBI pathophysiology has largely focused on adult injuries in males, limiting our understanding ofthe pathophysiological mechanisms of injury in the adolescent and female populations. This isimportant because males and females often report differential neurological symptoms and recoverytimeframes following mTBIs. Adolescent brain development is largely influenced by novel experienceswhich refine neurotransmission and neuronal circuit connectivity. Microglia are centrally important inthese processes through their phagocytic capacity to engulf, or prune, weak/unneeded synapses. Thesecells also adopt activated inflammatory phenotypes in response to brain injury, which could detract fromtheir neurodevelopmental functions. Our pilot data highlights interesting new data suggesting thatmicroglia density decreases following adolescent RmTBIs. This project aims to determine thespatiotemporal nature and cause of this phenomenon, and the resulting impact on neurodevelopmentalsynaptic pruning. Collectively, the outlined experiments in our project will produce new mechanisticinformation detailing the sex- and age-dependent effects of repetitive head injuries on glial cells andhighlight a potential new avenue for targeted interventions to decrease the socioeconomic burden ofRmTBIs in the Canadian and world populations. </body> </html>

View source data CIHR Funding Decisions Database (Canadian Institutes of Health Research)