Flora-Lee Bornette & Mélody Turcotte

Vaudreil-Dorion, QC

Second place at Expo-Science de Vaudreuil-Dorion

INTRODUCTION

Spinal fracture can affect the spinal cord. when this injury occurs, there are two types of impacts: physical and biological. We were interested in the immunological phenomena that arise during spinal cord injury: the transformation of astrocytes into toxic astrocytes and their consequences on oligodendrocytes. The attached picture (figure 1) shows these two types of nervous system cells, the toxic astrocytes and the oligodendrocytes, in action during this phenomenon.

SPINAL CHORD INJURY

The spinal cord (figure 2) is a fragile cylindrical tube situated at the center of the spine. It links the brain stem to the rest of the body thanks to neurons, which constitute the peripheral nervous system (PNS) (Association française contre les neuropathies périphériques, 2017). It allows for the transmission of messages coming from the brain towards other parts of the organism. This structure is important, as it induces vital functions: sensory function, motor function and reflexes. The location and depth of the injury can have disastrous consequences such as paralysis. This injury is often caused by a severe fall or driving accident. The symptoms, passing or definitive, associated with this accident are the loss of function of certain organs (such as the bladder or intestines), of muscle strength and of feeling (Wilberger & Mao, 2019).

IMPLICATED CELLS

To better understand the immunological phenomena of spinal cord injuries, we must understand the role of astrocytes and oligodendrocytes, glial cells which form the environment of neurons (figure 3). Situated at the center of the central nervous system (CNS) the role of these cells is primarily to balance the chemical and electrical environment of neurons by eliminating their waste and providing them with nutrients (Futura Santé, n.d.a).

As for astrocytes (figure 4), they are star-shaped cells participating in the maintenance of the blood-brain barrier; a barrier that serves as a filter and protection for the brain against pathogenic agents. Additionally, they participate in neurotransmission and the detoxification of nervous tissues (cleaning of toxic substances). All these roles allow for the proper functioning of the organism. Among these include scarring and the repair of the nervous system when it is injured (“Astrocyte,” 2020).

As for oligodendrocytes, they function by creating the myelin sheath for neuronal axons (figure 5). They wrap themselves around the axon, creating a thick shell that encloses the lipids and proteins necessary to neurons. By isolating the axon of each neuron, the myelin sheath allows for better transmission of nerve impulses, therefore an increase in information propagation speed by way of an electrical signal transmitted from one neuron to another (“Oligodendrocyte,” 2019).

TRANSFORMATION

To facilitate the comprehension of this text, we will refer to “good cells” when speaking about astrocytes, “destructive cells” for toxic astrocytes and “victim cells” for oligodendrocytes.

In 2017, a notable discovery was made by Dr. Ben Barres’ team (Liddelow, 2017): good cells can become toxic when certain signals are transmitted to them during spinal cord injury. This phenomenon is not completely understood by scientists, as it was only discovered three years ago. However, we know the primary source of these signals: microglia (Liddelow et al., 2017). Microglia are macrophages, which are white blood cells, situated in tissues of the central nervous system (brain and spinal cord). It is the sole defense of this system. When there is a spinal cord injury, microglia operate under their role of immune defense by sending three signals (see the following section) to astrocytes to create the inflammation necessary to heal the victim of the injury (Bairamian, 2018). During this inflammatory mechanism, the sending of these three signals to good cells that take care of scarring of the spinal cord injury triggers a state of stress transforming good cells into destructive cells (Bretheau, 2019b). This stress then causes the death of victim cells in their environment and therefore of the myelin which they constitute, weakening surrounding neurons (Li et al., 2016).

SIGNALS

While the three signals secreted by microglia play a positive and important role in the human body, they also have negative consequences on good cells, during spinal cord injury (Bretheau, 2019b).

Interleukin 1 alpha is an inflammatory cytokine (signal) (Simon, 2009), that triggers the inflammation process (“Interleukine 1,” 2020). It is present primarily in the microglia and is the principal signal implicated in the transformation of astrocytes to toxic astrocytes (Bretheau, 2019b).
Tumour Necrosis Factor is a protein of the immune system that helps coordinate cells, namely lymphocytes and neutrophils, during the inflammatory process. These cells are white blood cells which must defend, immunologically, the body from danger. It is this fight that the body must win that creates the inflammation necessary for healing of the victim (DerSarkissian, 2020).
Complement component 1q (Wener, 2007) is a glycoprotein which can link itself to cell receptors which are found on numerous cells surfaces such as those of lymphocytes (white blood cells) and fibroblasts (conjunctive tissue cells) (“Fibroblaste,” 2020) as well as on intracellular membranes such as mitochondrial membranes. This linkage can then induce phagocytosis: an immune defense mechanism (“Phagocytose,” 2020) and chemotaxis that plays a role in the functioning and development of multicellular organisms (“Chimiotaxie,” 2020).

These signaling molecules are called DAMPs (Danger associated Molecular Pattern)(Bretheau, 2019b). They are the first factors released in response to stress conditions. They initiate a danger signal to warn the body. It is the sending of these three signals, while necessary for healing of victim cells and the overall healing process, that stress good cells and transforms them into destructive cells (Bretheau, 2019b).

SUMMARY

The microglia trigger a natural inflammatory mechanism of which the initial purpose is to clean waste, but also provokes a degeneration of victim cells by destructive cells. Because this transformation is activated by signals, we can find these destructive cells in various contexts where these same signaling molecules are released (Bretheau, 2019b). It is implicated in these situations which affect the nervous system such as spinal cord injury but also in many other neurodegenerative diseases such as Parkinson’s disease, multiple sclerosis, Amyotrophic Lateral Sclerosis and Alzheimer’s disease (Kinney et al., 2018). Even if this loss of victim cells does not have large scale impact, the destruction of the myelin sheath reduces the speed and quality of nerve impulses, therefore the quality of neurological transmissions.

CONCLUSION

According to recent research, certain signals sent to astrocytes, during spinal cord injury, can transform them into toxic astrocytes. This discovery indicates that a cell can deviate from its primary function and harm certain important functions of the human body. According to researcher Floriane Breteau, “A better understanding of this mechanism could help accident victims recover better.” (Bretheau, 2019a). In order to diminiish the damages due to spinal cord injury, we could either attempt to block toxic signals to reduce the emergence of toxic astrocytes or stimulate the emergence of new oligodendrocytes to replace those damaged or destroyed (Bretheau, 2019b).

FIGURES

**Figure 1**: Immunofluorescence of astrocytes and oligodendrocytes cultured in vitro
*Source: Bretheau (2019a)*
**Legend:**
Astrocytes – green
Oligodendrocytes – red and blue

**Figure 2**: Structure of the Spine
*Source: Godlman (2018)*

**Figure 3**: Neuron
*Source: Futura Santé (n.b.d.)*

**Figure 4**: Astrocyte
*Source: Bagalà (2018)*

**Figure 5**: Oligodendrocyte
*Source: “Oligodendrocyte” (2010)*

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Spinal Chord Injury