Diffuse Axonal Injury in the Rat Brain: Axonal Injury and Oligodendrocyte Activity Following Rotational Injury.

Michela Losurdo,Mattias K Sköld,Johan Davidsson

doi:10.3390/brainsci10040229

Michela Losurdo, Mattias K Sköld + Show 1 more

Open Access

https://doi.org/10.3390/brainsci10040229

Copy DOI

Abstract

Traumatic brain injury (TBI) commonly results in primary diffuse axonal injury (DAI) and associated secondary injuries that evolve through a cascade of pathological mechanisms. We aim at assessing how myelin and oligodendrocytes react to head angular-acceleration-induced TBI in a previously described model. This model induces axonal injuries visible by amyloid precursor protein (APP) expression, predominantly in the corpus callosum and its borders. Brain tissue from a total of 27 adult rats was collected at 24 h, 72 h and 7 d post-injury. Coronal sections were prepared for immunohistochemistry and RNAscope® to investigate DAI and myelin changes (APP, MBP, Rip), oligodendrocyte lineage cell loss (Olig2), oligodendrocyte progenitor cells (OPCs) (NG2, PDGFRa) and neuronal stress (HSP70, ATF3). Oligodendrocytes and OPCs numbers (expressed as percentage of positive cells out of total number of cells) were measured in areas with high APP expression. Results showed non-statistically significant trends with a decrease in oligodendrocyte lineage cells and an increase in OPCs. Levels of myelination were mostly unaltered, although Rip expression differed significantly between sham and injured animals in the frontal brain. Neuronal stress markers were induced at the dorsal cortex and habenular nuclei. We conclude that rotational injury induces DAI and neuronal stress in specific areas. We noticed indications of oligodendrocyte death and regeneration without statistically significant changes at the timepoints measured, despite indications of axonal injuries and neuronal stress. This might suggest that oligodendrocytes are robust enough to withstand this kind of trauma, knowledge important for the understanding of thresholds for cell injury and post-traumatic recovery potential.

Highlights

Traumatic brain injury (TBI) is an important public health problem and is the leading cause of disability and death among young adults [1,2]
While qualitative analysis was performed through visual analysis of immunohistochemistry slides for all selected markers, quantitative analysis was performed by image analysis of IHC slides for amyloid precursor protein (APP) and Rip expression, and of RNAscope® slides for Olig2 and PDGFRa expression with Fiji ImageJ
Having confirmed that this rotational model of TBI induces diffuse axonal injury (DAI), we investigated the oligodendrocyte population to assess how they react to rotational TBI and whether they are robust enough to survive this type of relatively mild, diffuse injury

Summary

Introduction

Traumatic brain injury (TBI) is an important public health problem and is the leading cause of disability and death among young adults [1,2]. When the head is exposed to rotational accelerations, common in sports-related accidents and in road traffic accidents, the brain lags behind in a non-homogeneous way [3,4], producing shearing and strain of the brain tissues. Brain Sci. 2020, 10, 229 different stiffness properties, e.g., the border between the corpus callosum and cortex, where large concentrations of injured cells are found [5]. Rotational accelerations of the head, here referred to as rotational TBI, may lead to tissue loadings that could produce primary axotomy. At the time of injury, axons may be stretched and undergo cytoskeletal damage due to neurofilament compaction and mechanoporation of the cell membrane, which results in membrane leakage, ionic disturbances, and osmotic imbalance [5,10]

Objectives

Methods

Results

Discussion

Conclusion