Cytokines and Sickness Behavior
Alan J. Husband in Psychoimmunology CNS-Immune Interactions, 2019
The classical view, however, is that IL-1 and other cytokines enter the brain at sites where the blood-brain barrier is absent, such as the circumventricular organs. Circumventricular organs are specialized neural structures that lie outside the blood-brain barrier and have both sensory and neurosecretory functions.39 One of these structures is the organum vasculosum of the lamina terminalis (OVLT). It is located within the rostral wall of the third ventricle and adjacent to the septum and preoptic area. This vascular rich organ is devoid of the typical tight junctions that normally prevent the passage of large molecules through vascular cell walls. Lesions of this organ have been found to either block or enhance pyrogen-induced fevers. A possible explanation for these seemingly contradictory results is that the damage caused by the lesion is accompanied by a temporary increased permeability of the blood vessels at the site of the injury. Another possibility is the participation of non-neuronal elements such as astrocytes in the generation of the mediators (e.g., PGE) that are responsible for the neural effects of pyrogens.
Anatomy for neurotrauma
Hemanshu Prabhakar, Charu Mahajan, Indu Kapoor in Essentials of Anesthesia for Neurotrauma, 2018
In the central nervous system, the capillary endothelium and the perivascular feet of the astrocytes of neurons, form a highly selective semipermeable membrane barrier, termed the blood–brain barrier, which helps in maintaining a chemically optimal environment for neuronal function. This blood–brain barrier controls movements of ions and metabolites, most importantly glucose, across the brain, and also prevents entry of harmful substances or toxins into the central nervous system. The blood–brain barrier may break down following infection or ischemia, leading to cytotoxic edema. Some areas of the brain, such as the pineal body, posterior pituitary, area postrema, median eminence of hypothalamus and so on, are devoid of the blood–brain barrier, and are termed circumventricular organs.
Chronic Fatigue Syndrome: Limbic Encephalopathy in a Dysregulated Neuroimmune Network
Jay A. Goldstein in Chronic Fatigue Syndromes, 2020
It has been difficult to demonstrate a progesterone abnormality consistently in PMS, but the pulsatile nature of luteinizing hormone (LH) secretion may be dysregulated. The GnRH control over LH secretion is modulated in part by endogenous opioids. IL-1 may exert many of its limbic effects through endogenous opioids,72 since some of its hypothalamic actions can be blocked by naloxone. If CFS is, in part, a disorder of cytokine dysregulation, IL-1 could be secreted by the hippocampus and affect the hypothalamus, or it could gain slow access from the periphery via the circumventricular organs: area postrema, organum vasculosum, choroid plexus (which also manufactures IL-1), pineal gland (perhaps not involved in PMS since melatonin biosynthesis is not abnormal in PMS), and median eminence. A bidirectional transport of IL-1 alpha across the blood-brain-barrier (BBB) has been demonstrated,73 although this finding has not been confirmed by others. The hypothalamus had the highest entry rate. Activated T-lymphocytes may also cross the BBB and release IL-1 (and presumably other cytokines) into particular sites. The circumventricular organs may also function as neuronal transducers of circulating peripheral neuropeptides and cytokines, manufacturing them without allowing their ingress.74
Basic physiology of the blood-brain barrier in health and disease: a brief overview
Published in Tissue Barriers, 2021
Mehmet Kaya, Bulent Ahishali
In contrast to the capillaries located in the brain parenchyma, blood microvessels in the circumventricular organs do not display barrier properties. The endothelial cells of these microvessels have fenestrae, which allow the free diffusion of substances between the blood and CNS.37,213,214 These organs consist of secretory structures like pineal gland, subcommisural organ, median eminence, and choroid plexuses and sensory regions, including area postrema, subfornical organ, and organum vasculosum of the lamina terminalis.215 The exchange of hormones and other molecules between the circulation and CNS is accomplished mainly in circumventricular organs in which increased vascularization facilitates the sensory and secretory roles to mediate the communication between the brain and the periphery.215,216
Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health
Published in Gut Microbes, 2020
Aimée Parker, Sonia Fonseca, Simon R. Carding
The term “blood-brain barrier” was first coined by Stern and Gautier,16 who examined the penetration or exclusion of compounds, such as morphine or India ink, between blood and brain, and proposed a role for the barrier in maintaining brain homeostasis. Later studies in the 1960s demonstrated that the BBB was located in the endothelium forming the walls of vessels in the brain.17,18 Since these pioneering studies, the concept of the BBB as a static, impermeable barrier has evolved into the current view of a dynamic, highly regulated, specific cellular system,19 with increasing awareness of the contribution multiple cell types play in regulating dynamic BBB responses. The BBB is now considered to be part of a neurovascular unit (NVU) (Figure 1) comprising brain microvascular endothelial cells (BMEC), pericytes, astrocytes, neurons, microglia, and extracellular matrix (ECM),20 which together contribute to regulating BBB stability and function. This organization is found in all brain regions, except for the circumventricular organs, which regulate the autonomic nervous system and endocrine glands and have fenestrations allowing the diffusion of molecules across vessel walls.21
Postnatal melatonin treatment protects against affective disorders induced by early-life immune stimulation by reducing the microglia cell activation and oxidative stress
Published in International Journal of Neuroscience, 2018
I. Berkiks, H. Benmhammed, A. Mesfioui, A. Ouichou, A. El hasnaoui, S. Mouden, T. Touil, Y. Bahbiti, R. Nakache, A. El hessni
Early-life adversity is an established risk factor for the development of neurodegenerative and neurodevelopment disorders. Stress, inflammation and toxin exposition during the early life can lead to changes in brain development, neurocircuits and behaviors. Several studies showed that the early-life immune stimulation of the brain could alter the affective and cognitive behavior at the adult age [1]. The peripheral inflammation can also reach the brain through blood–brain barrier (BBB) disruption, circumventricular organs and the nerve pathway or endothelial cell communication. Once in the central nervous system (CNS) parenchyma, neuroinflammation can trigger microglia and astroglia activation and subsequent pro-inflammatory cytokine production such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) and INFg [2].
Related Knowledge Centers
- Area Postrema
- Median Eminence
- Ventricular System
- Capillary
- Brain
- Posterior Pituitary
- Vascular Permeability
- Blood–Brain Barrier
- Subfornical Organ
- Vascular Organ of Lamina Terminalis