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.

Novel adult cortical neuron processing and screening method illustrates sex- and age-dependent effects of pharmaceutical compounds

“…Considering the many epigenetic 78 , 79 and metabolic 21 changes occurring in neurons as they age, the age-factor should be considered during screenings. For example, pro-inflammatory cytokines deemed harmful to adults are beneficial for the development of young neurons 25 and changes in mitochondrial functions impact SCI in an age-dependent manner 80 . Therefore, compounds that modulate cytokine production or mitochondrial functions may produce age-dependent effects 80 .…”

“…Current therapeutic strategies in neurodegenerative diseases, such as glaucoma and Parkinson’s disease, aim at increasing axon regenerative capacity to mitigate pathology 19 , 20 . Aging itself reduces neurite regenerative capacity 21 and increases susceptibility of neurons to death and degeneration 22 , which can produce worse outcomes after neurotrauma 23 and increase the prevalence of neurodegenerative diseases 24 , 25 . Therefore, it is imperative that novel therapeutic strategies can increase the survival and neurite regenerative capacity of neurons in older individuals as well.…”

Novel Adult Cortical Neuron Processing and Screening method illustrates Sex- and Age-dependent effects of pharmaceutical compounds

“…Considering the many epigenetic 71,72 and metabolic 21 changes occurring in neurons as they age, the age-factor must be considered during screenings. For example, pro-inflammatory cytokines deemed harmful to adults are beneficial for the development of young neurons 25 . Therefore, compounds that modulate cytokine production are expected to produce age dependent effects.…”

“…Current therapeutic strategies in neurodegenerative diseases, such as glaucoma and Parkinson’s disease, aim at increasing axon regenerative capacity to mitigate pathology 19,20 . Aging itself reduces neurite regenerative capacity 21 and increases susceptibility of neurons to death and degeneration 22 which can produce worst outcomes after neurotrauma 23 and increases the prevalence of neurodegenerative diseases 24,25 . Therefore, it is imperative that novel therapeutic strategies can increase the survival and neurite regenerative capacity of neurons in older individuals as well.…”

Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Accelerate Functional Recovery After Spinal Cord Injury by Promoting the Phagocytosis of Macrophages to Clean Myelin Debris

“…Spinal cord injury (SCI) is a devastating event that may result in permanent damage to sensation and motor functions below the injured site of the spinal cord ( Huang et al, 2020a ; Li Y. et al, 2020 ; Zrzavy et al, 2021 ). SCI provokes an inflammatory response after primary injury consisting of activated resident and infiltrating immune cells ( Sefiani and Geoffroy, 2021 ). A remarkable feature of the inflammatory processes in SCI is the infiltration of monocyte-derived macrophages (MDMs) from the circulation to the lesion site ( David et al, 2018 ).…”