Maturation, Barrier Function, Aging, and Breakdown of the Blood–Brain Barrier
Shamim I. Ahmad in Aging: Exploring a Complex Phenomenon, 2017
Astrocytes are glial cells that help support and protect neurons by controlling neurotransmitter and ion concentrations to maintain the homeostatic balance of the neural microenvironment, modulating synaptic transmission, and regulating immune reactions (Rodriguez-Arellano et al. 2016). Astrocytes are also known to interact with ECs through their end feet projections that encircle the abluminal side of cerebral capillaries (Abbott et al. 2006). In the adult brain, such interactions are important in synchronizing metabolite levels with cerebral blood flow and vasodilation, and regulating brain water content (Zlokovic 2008). For example, the most abundant water channel protein, aquaporin 4, is predominantly expressed in astrocytic end feet surrounding CNS vessels (Tait et al. 2008). Astrocytes are also a key cellular support of BBB integrity. Recent in vitro and in vivo molecular studies have revealed several effector molecules released by astrocytes that function to enhance and maintain barrier tightness (Keaney and Campbell 2015).
Neuropathology
Burkhard Madea in Asphyxiation, Suffocation,and Neck Pressure Deaths, 2020
Oedema develops as a result of the rapid drop in oxidative metabolism in the neurons, the glia, the endothelial cells of the blood vessels and the choroid plexus. The abrupt lack of energy leads to the breakdown of homeostatic conditions. In the acute hypoxic−ischaemic phase, the ion pump of the neuroglia and neurons, in particular the activity of the Na+/K+−ATPase, quickly comes to a standstill. As a result, the Na+ concentration increases intracellularly and the K+ concentration decreases. The resulting membrane depolarization leads to Cl− influx into the cells. Due to osmosis, water reaches the intracellular space and the cells swell. The glial cells in particular absorb water in order to compensate for the intracellular increase in osmolarity. Aquaporin-4 obviously plays a role as a mediator. This intracellular oedema, called cytotoxic oedema, occurs first. The subsequent collapse of the blood−brain barrier causes the formation of vasogenic oedema. As a result, proteins are transported extravasally and draw water into the interstitial space through osmosis. As a result, the volume of the interstitial space increases [2, 4, 5].
Outdoor Air Pollution
William J. Rea, Kalpana D. Patel in Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
Two-photon imaging of live mice through a closed cranial window has since permitted the direct observation of CSF movement through the intact brain. This technique revealed that CSF is exchanged rapidly with interstitial fluid (ISF) in the brain by a highly organized, brain-wide pathway that consists of three serial elements: a para-arterial CSF influx route, a paravenous ISF clearance route, and an intracellular trans-astrocytic path that couples the two extracellular paravascular routes.7 Specifically, CSF passes through the para-arterial space that surrounds arteries; the space is bound by the abluminal surface of the blood vessel and the apical processes of astrocytes. Water channels called aquaporin 4 (AQP4) on the vascular endfeet of astrocytes8 facilitate convective flow out of the para-arterial space and into the interstitial space (Figure 2.1).
Tramadol administration induced hippocampal cells apoptosis, astrogliosis, and microgliosis in juvenile and adult male mice, histological and immunohistochemical study
Published in Ultrastructural Pathology, 2020
Ola A. Hussein, Asmaa Fathi Abdel Mola, Amal Rateb
In normal brain, this astrogliosis has an important role in different processes as regulation of ion homeostasis, production, and secretion of trophic/inflammatory factors, repair, and regeneration of cell/tissue and maintenance of blood-brain barrier.46 However, the induced astrogliosis by chronic drug abuse is considered as a response of the innate immunity to the neurotoxicity and brain injury47 which may lead to changes in synaptogenesis and neurogenesis.48,49 According to previous studies50,51, opioid signaling and information processing in the brain were found to induce the activation of glial cells especially astrocytes by direct stimulation of mu receptors in astrocyte membranes.52 In addition, the effects of opioids might be mediated by its ability to activate the protein aquaporin-4. Protein aquaporin-4 is located to the astrocytic end feet that wrap blood vessels and is considered as an important water channel for the regulation of brain water and amino acid.53 Furthermore, astrogliosis due to opioid abuse can promote apoptosis and/or necrosis by increasing Ca2+ with the subsequent production of carbonyl oxidation.54
Emerging drugs for the acute treatment of relapses in adult neuromyelitis optica spectrum disorder patients
Published in Expert Opinion on Emerging Drugs, 2022
Edgar Carnero Contentti, Pablo A. López, Juan I. Rojas
Neuromyelitis optica spectrum disorders (NMOSD) are rare but often devastating neuroinflammatory autoimmune diseases of the central nervous system (CNS) associated to pathogenic serum aquaporin-4 antibodies (AQP4-Ab) in the majority of patients [1,2]. NMOSD is characterized mainly by severe relapses of optic neuritis (ON), transverse myelitis (TM), brainstem and/or cerebral syndromes [3]. Phenotypically, 90% of NMOSD patients experience a relapsing course over time, while a progressive clinical course is uncommon [1–3]. Neurologic disability typically accumulates with each clinical relapse, resulting in short- and long-term impairment of motor and/or visual functions, as well as affecting other organ systems [1–4]. In this regard, 41% of patients remain blind in one eye after an ON, 17% severely paralyzed (bedridden) following a TM relapse and 25% remain significantly disabled (cane dependent) [5]. Importantly, NMOSD relapses have been associated with mortality when primary relapses involve the brainstem or cervical lesions extend and include the medulla, ultimately increasing the risk of respiratory failure, particularly in patients with African ancestry [6]. Long-term outcomes from relapses were strongly associated with the severity of the attack at disease onset, regardless of acute treatment timing [7,8] and the initial onset attack [5]. Thus, severity of the relapses before an initial treatment was an independent predictor for subsequent relapses after adjusting treatments [5,9].
Neuromyelitis Optica Spectrum Disorder and Uveitis
Published in Ocular Immunology and Inflammation, 2022
Andrew R. Carey, J. Fernando Arevalo
Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare demyelinating disease of the central nervous system associated with aquaporin-4 (AQP4) IgG auto-antibodies, which induce complement activation. It has similar presentation to multiple sclerosis (MS) with relapsing and remitting episodes of central nervous system (CNS) demyelination, although the underlying mechanism is different and more similar to Behcet's disease.1,2 Updated diagnostic criteria in 2015 separated diagnostic criteria into AQP4-positive patients requiring 1 core clinical characteristic or those without AQP4 antibodies requiring 2 core clinical characteristics; the core clinical characteristics are optic neuritis, acute myelitis, area postrema syndrome, acute brainstem syndrome, symptomatic narcolepsy or acute diencephalic clinical syndrome, and symptomatic cerebral syndrome with typical MRI lesions.3 MS has been associated with a rare form of intraocular inflammation, namely, intermediate uveitis, while Behcet's disease has also been associated with uveitis although more typically develops posterior uveitis and retinal vasculitis.
Related Knowledge Centers
- Aquaporin
- Central Nervous System
- Cerebellum
- Cerebrospinal Fluid
- Integral Membrane Protein
- Monomer
- Astrocyte
- Cell Membrane
- Gene
- X-Ray Crystallography