Non-Communicable Neurological Disorders and Neuroinflammation

Abstract

Traumatic brain injury, stroke, and neurodegenerative diseases represent a major cause of morbidity and mortality in Africa, as in the rest of the world. Traumatic brain and spinal cord injuries specifically represent a leading cause of disability in the younger population. Stroke and neurodegenerative disorders predominantly target the elderly and are a major concern in Africa, since their rate of increase among the ageing is the fastest in the world. Neuroimmunology is usually not associated with non-communicable neurological disorders, as the role of neuroinflammation is not often considered when evaluating their cause and pathogenesis. However, substantial evidence indicates that neuroinflammation is extremely relevant in determining the consequences of non-communicable neurological disorders, both for its protective abilities as well as for its destructive capacity. We review here current knowledge on the contribution of neuroinflammation and neuroimmunology to the pathogenesis of traumatic injuries, stroke and neurodegenerative diseases, with a particular focus on problems that are already a major issue in Africa, like traumatic brain injury, and on emerging disorders such as dementias.

Keywords: alzheimer’s disease; neuroinflammation; spinal cord injury; stroke; traumatic brain injury.

Figure 1

In response to danger-associated molecular patterns (DAMPs), and other extracellular signals released by injured neurons, microglia can become polarized towards pro-inflammatory M1-like and anti-inflammatory M2-like activation states that can have distinct roles in neurodegeneration and tissue repair. M1-like microglia release pro-inflammatory cytokines, chemokines and free radicals that impair brain repair and contribute to chronic neuroinflammation, oxidative stress and long-term neurological impairments. M2-like microglia release anti-inflammatory cytokines, neurotrophic factors and proteases, and they have increased phagocytic activity. M2-like microglia promote immunosuppression and resolution of M1mediated neuroinflammation, and participate in CNS remodeling and repair by modulating neurorestorative processes such as neurogenesis, angiogenesis, oligodendrogenesis and remyelineation. However, there is much overlap between and M1 and M2 like cellular responses. DAMPs, danger-associated molecular patterns; PRR, pathogen recognition receptors; TLR, toll-like receptors. Modified from (1). Reproduced with permission.

Figure 2

As compared to controls (right panel), reactive astrogliosis can be appreciated as an increased GFAP reactivity and morphological changes in astrocytes 6 months after brain injury. These changes are likely to affect the blood-brain barrier and the glymphatic system and thus the clearance of potentially toxic substances such as tau.