Innate Immunity Cells and the Neurovascular Unit

Abstract

Recent studies have clarified many still unknown aspects related to innate immunity and the blood-brain barrier relationship. They have also confirmed the close links between effector immune system cells, such as granulocytes, macrophages, microglia, natural killer cells and mast cells, and barrier functionality. The latter, in turn, is able to influence not only the entry of the cells of the immune system into the nervous tissue, but also their own activation. Interestingly, these two components and their interactions play a role of great importance not only in infectious diseases, but in almost all the pathologies of the central nervous system. In this paper, we review the main aspects in the field of vascular diseases (cerebral ischemia), of primitive and secondary neoplasms of Central Nervous System CNS, of CNS infectious diseases, of most common neurodegenerative diseases, in epilepsy and in demyelinating diseases (multiple sclerosis). Neuroinflammation phenomena are constantly present in all diseases; in every different pathological state, a variety of innate immunity cells responds to specific stimuli, differentiating their action, which can influence the blood-brain barrier permeability. This, in turn, undergoes anatomical and functional modifications, allowing the stabilization or the progression of the pathological processes.

Innate Immunity: A Common Denominator between Neurodegenerative and Neuropsychiatric Diseases

“…Our group recently reviewed various immunological mechanisms involved in AD [4], highlighting the role of microglia and chronic low-grade inflammatory stimuli, which produce different levels of immune dysregulation depending on the stage of the disease. Neuroinflammation is not simply a reactive response activated by incoming senile plaques and neurofibrillary tangles, but instead contributes as much to pathogenesis as do plaques and tangles [15].…”

“…Tissue injuries can cause MC degranulation and the release of cytokines and other molecules that can trigger the inflammatory response. MCs are involved in many pathological processes in the CNS or elsewhere, both by secreting pro-inflammatory cytokines and by the action of enzymatic factors [4].…”

Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

“…[21][22][23] Now, the NVU is a tool that can be used to understand normal brain physiology as well as the pathophysiology of numerous neurological disorders. [24][25][26][27][28][29] Conversely, the malfunction of astroglia in the NVU (i.e., "astrogliopathy") [30][31][32][33][34] induces neuronal dysfunction, leading to various neurological disorders including cerebrovascular disease (e.g., stroke and small vessel disease-like Binswanger's disease and cerebral autosomaldominant arteriopathy with subcortical infarct and leukoencephalopathy [CADASIL]/ 35 cerebral autosomal recessive arteriopathy with subcortical infarct and leukoencephalopathy [CARASIL]), 36,37 neurodegenerative disease (e.g., Alzheimer's disease, 38,39 Parkinson's disease, 40,41 and amyotrophic lateral sclerosis [ALS]), [42][43][44] and neuroimmunological disease (e.g., multiple sclerosis [MS], [45][46][47][48] and neuromyelitis optica spectrum disorder [NMOSD]). 49,50 This review will focus on the supportive roles of astroglia in the NVU from the perspective of three major metabolic compartments with neurons: (i) glucose and lactate; (ii) fatty acid and ketone bodies (KBs); and (iii) D-and L-serine.…”

Perivascular Unit: This Must Be the Place. The Anatomical Crossroad Between the Immune, Vascular and Nervous System

“…Endothelial cells lining the cerebral blood vessels represent one of the critical layers of the blood-brain barrier (BBB), which controls access of cells and molecules to the brain parenchyma. Transcytosis is limited by the lack of fenestrae in the endothelial cell layer (Iadecola, 2004) and paracellular transport of ions, macromolecules and other solutes is restrained by a tight interendothelial seal, mainly provided by tight junctions (Hawkins et al, 2006;Presta et al, 2018) made of transmembrane proteins coupled to the cytoskeletal actin (Stamatovic et al, 2016). As a result, most immunocompetent cells cannot access the brain parenchyma under physiological conditions, a phenomenon known as immune privilege.…”