Changes in Brain Neuroimmunology Following Injury and Disease

Abstract

The nervous and immune systems are intimately related in the brain and in the periphery, where changes to one affect the other and vice-versa. Immune cells are responsible for sculpting and pruning neuronal synapses, and play key roles in neuro-development and neurological disease pathology. The immune composition of the brain is tightly regulated from the periphery through the blood-brain barrier (BBB), whose maintenance is driven to a significant extent by extracellular matrix (ECM) components. After a brain insult, the BBB can become disrupted and the composition of the ECM can change. These changes, and the resulting immune infiltration, can have detrimental effects on neurophysiology and are the hallmarks of several diseases. In this review, we discuss some processes that may occur after insult, and potential consequences to brain neuroimmunology and disease progression. We then highlight future research directions and opportunities for further tool development to probe the neuro-immune interface.

Keywords: blood-brain barrier; contusions; extracellular matrix; glioblastoma; multiple sclerosis; neuro-immunology; stroke.

Figure 1

Illustration of the various components comprising the brain extracellular matrix (brain ECM) and the blood-brain barrier (BBB). The brain ECM is the combination of the ECM in the central nervous system (neuro-ECM), the basement membrane (BM), and the luminal ECM (also called the glycocalyx). The BBB is the combination of the BM, luminal ECM, and astrocytes, pericytes, and endothelial cells. Figure made with Biorender.

Figure 2

Illustration highlighting some of the cellular or molecular pathways involved in (A) contusions or stroke, (B) glioblastoma (GB), and (C) multiple sclerosis (MS), with events that occur under comparable time scales grouped together. (A) BBB permeabilization and the role of microglia are highlighted. (B) Changes in the brain tumor microenvironment and some neuro-immune consequences. (C) Lymphocyte trafficking into the CNS and subsequent demyelination in MS. Figure made with Biorender.