10 Chapter 1 Neuroinflammation in the central nervous system The prevalence of neuroinflammatory and neurodegenerative diseases highly depends on the country surveyed, yet the most prevalent disease globally is dementia, with an estimated incidence of 9.33% worldwide1. The increase in the incidence of dementia, as with many neurodegenerative diseases, is in part due to the ageing population3, since an ageing brain, or one following peripheral infections or other insults is ‘primed’ to render the central nervous system (CNS) more susceptible to damage4. Although neurodegenerative and neuroinflammatory diseases often have different aetiologies, a common feature is chronic activation of innate immune cells within the CNS, mainly microglia (Table 1), and in other diseases such as multiple sclerosis (MS), also the influx of peripheral immune cells across the blood-brain barrier (BBB). Microglia can be implicated as the primary cause of neuropathology in many CNS diseases and can induce neuronal cell death through both direct and indirect pathways. For example, when microglia are activated by infectious pathogens, aggregated proteins or superoxides, they can cause excitotoxic neuronal death by expressing iNOS, releasing glutamate or proteases such as cathepsins or matrix metalloproteases5. Additionally, activated microglia release tumor necrosis factor (TNF) increasing neuronal apoptosis5. Innate immunity in the CNS, and specifically microglia and astrocytes, are becoming increasingly implicated in neuropathology of CNS diseases due to the exponential increase of knowledge on microglia and astrocyte biology over the past decade. Due to this, there is an increasing need to monitor glial cell behaviour in vivo in patients during disease progression but also in response to therapies. Innate immunity in the brain Innate immunity is the first line of defence in infection, but also plays a key role in tissue repair, clearance of apoptotic cells and cellular debris as well as in response to tumours. While the key innate immune cells in the CNS are microglia and astrocytes, peripheral macrophages as well as oligodendrocytes contribute to innate immune responses in the CNS. Additionally, the immune system in the CNS is unique in that mostly occurs behind several CNS barriers (Figure 1). A B Astrocyte Basal Lamina Pericyte Endothelial cell Interneuron Macrophage T-cell Tight Junction Fenestrated blood vessel Choroid plexus epithelium Ependymal layer CSF Stroma CNS parenchyma Epithelial basal membrane Figure 1. Blood–central nervous system (CNS) barriers. The blood–brain barrier (BBB) (a) and blood–spinal cord barrier (BSCB) limit potential immune cells, antibodies and soluble factors entering the CNS in health. Likewise, while the choroid plexus (CP) also limits cell migration, evidence suggests that regulatory T‐cells enter the brain via the CP (b) during health in order to ensure surveillance of the CNS. CSF, cerebrospinal fluid.
RkJQdWJsaXNoZXIy MTk4NDMw