The Potential Role of Inflammation in Modulating Endogenous Hippocampal Neurogenesis After Spinal Cord Injury

Abstract

Currently there are approximately 291,000 people suffering from a spinal cord injury (SCI) in the United States. SCI is associated with traumatic changes in mobility and neuralgia, as well as many other long-term chronic health complications, including metabolic disorders, diabetes mellitus, non-alcoholic steatohepatitis, osteoporosis, and elevated inflammatory markers. Due to medical advances, patients with SCI survive much longer than previously. This increase in life expectancy exposes them to novel neurological complications such as memory loss, cognitive decline, depression, and Alzheimer's disease. In fact, these usually age-associated disorders are more prevalent in people living with SCI. A common factor of these disorders is the reduction in hippocampal neurogenesis. Inflammation, which is elevated after SCI, plays a major role in modulating hippocampal neurogenesis. While there is no clear consensus on the mechanism of the decline in hippocampal neurogenesis and cognition after SCI, we will examine in this review how SCI-induced inflammation could modulate hippocampal neurogenesis and provoke age-associated neurological disorders. Thereafter, we will discuss possible therapeutic options which may mitigate the influence of SCI associated complications on hippocampal neurogenesis.

Keywords: inflammation; memory and cognitive impairment; neurogenesis; spinal cord injury; therapeutics.

FIGURE 1

Health complications associated with chronic SCI. The potential health complications developing after SCI have been categorized into major sections with the specific complications in the respective category listed underneath.

FIGURE 2

Temporal relationship between SCI and rate of hippocampal neurogenesis. Dehler et al. presented a 37% increase 2 days post injury (dpi), 99% increase 14 dpi, and 28% decrease 91 dpi in the number of DCX+ neurons in the dentate gyrus in a T8 80% transection model on 12-week-old mice (Dehler et al., 2018). Felix et al. reported a 40% decrease 15 and 90 dpi in the number of BrdU+/DCX+ neurons in the dentate gyrus in a C2 left transection in 16-week-old rats (Felix et al., 2012). Jure et al. illustrated a 71% decrease in the number of DCX+ neurons in the dentate gyrus 60 days after severe T8 compression on 8-week-old rats (Jure et al., 2017), and 24% and 42% decrease in the number of DCX+ neurons in the dentate gyrus 7 and 50 days after moderate T8 compression, respectively, on 8-week-old mice. Wu et al. demonstrated a 36% and 52% reduction in the number of DCX+ neurons in the dentate gyrus 84 and 112 days after a moderate T9 contusion in 20-26g mice, respectively (Wu et al., 2014, 2016).

FIGURE 3

Therapeutic options to increase hippocampal neurogenesis. Illustrated here are several different categories of therapeutic options that have potential to alleviate the SCI induced reduction in hippocampal neurogenesis with specific treatment options and potential affects listed underneath each category.