Immunobiology of spinal cord injuries and potential therapeutic approaches

Abstract

The incidence of spinal cord injuries (SCI) is high every year. As the spinal cord is the highway that allows for the brain to control the rest of the body, spinal cord injuries greatly impact the quality of life of the patients. The SCI include the primary response consisting of the initial accident-induced damage and the secondary response that is characterized by damage due to inflammation and biological responses. Astrocytes are the first to act at the site of the injury, forming a glial scar and attracting immune cells. The immune system plays a role in cleaning out the debris caused by the injury, as well as preventing neurons to grow and heal. The secondary injury caused by the inflammatory response is the major target to combat SCI. This article critically reviews the key players in the inflammatory SCI response and potential therapies, specifically targeting astrocytes, neutrophils, and macrophages. These cells are both beneficial and detrimental following SCI, depending on the released molecules and the types of cells infiltrated to the site of injury. Indeed, depending on the subtype of macrophages, M1 or M2, beneficial or detrimental response could be incited. Therapeutic strategies to regulate and manipulate the immune cells via increasing or decreasing their recruitment to the site of injury could be developed together with upregulating and downregulating the release of certain chemicals from the infiltrated cells.

Potential immunotherapies for traumatic brain and spinal cord injury

“… 91 , 92 Astrocyte-specific inflammatory signaling plays a key role in the secondary injury after SCI and TBI. 93 , 94 , 95 NFκB signaling has been well known to participate the inflammatory response during the secondary CNS injury. It plays a dual role in the pathogenesis and functional recovery after CNS injury.…”

CRID3, a Blocker of Apoptosis Associated Speck Like Protein Containing a Card, Ameliorates Murine Spinal Cord Injury by Improving Local Immune Microenvironment

“…Previous studies have shown that under natural conditions, the local immune microenvironment of SCI is "Yin-Yang" imbalance, and inflammatory cell subsets (such as Th1, Th17, Tc and M1) and factors (such as IL-1b, IL-18, IL-6, IFN-g and TNF-a) are dominant, while anti-inflammatory cell subsets (such as Th2, Treg, Ts, M2, etc.) and factors (such as IL-4, − 10, − 13 and TGF-b) are very rare [5,6,[55][56][57][58][59]. This is an important mechanism of pathological damage following SCI.…”

“…Secondary injury refers to local inflammation, edema, ischemia and electrolyte changes, among which inflammation is one of the main damage factors [4,5]. The inflammatory response is characterized by infiltration and activation of inflammatory cells in the injured spinal cords, which leads to the increase of inflammatory cells and inflammatory factors, and formation of inflammatory microenvironment, finally leading to spinal cord dysfunction [6].…”

CRID3, a blocker of apoptosis associated speck like protein containing a card, ameliorates murine spinal cord injury by improving local immune microenvironment

“…Primary injury refers to the direct injury of mechanical force to the spinal cord, which cannot be interfered clinically [3]. Secondary injury refers to local inflammation, edema, ischemia, and electrolyte changes, among which inflammation is one of the main damage factors [4,5]. The inflammatory response is characterized by infiltration and activation of inflammatory cells in the injured spinal cords, which leads to the increase of inflammatory cells and inflammatory factors, and formation of inflammatory microenvironment, finally leading to spinal cord dysfunction [6].…”