Long COVID Conditions – Fatigue 03
ROLE OF VAGUS NERVE IN INFLAMMATION
There are two methods by which peripheral inflammation may exacerbate CNS inflammation: leaky regions in the blood-brain barrier and the vagus nerve. The vagus nerve, also known as the tenth cranial nerve, is the autonomic nervous system’s longest nerve. To moderate oxygen demand, this nerve has parasympathetic regulation of various organs involved in breathing, including the lungs, heart, and diaphragm, which might contribute to fatigue.
Afferents from the vagal nerve tend to transfer pro-inflammatory responses from cells in the peripheral organs to the CNS. From CNS signals, vagal efferents tend to produce anti-inflammatory responses in peripheral tissue. The vagal afferents transmit pro-inflammatory signals from the peritoneum and organs such as the lung, gut, ear, spleen, liver, and lung to trigger inflammatory cytokines in specific centers in the CNS. From these centers Pro-inflammatory signal from the periphery cause increase pro-inflammatory cytokine production in parts of the brain that impact tiredness and sleep.
In contrast, activation of the vagal efferents caused by cholinergic mechanisms in the brain, such as muscarinic acetylcholine receptors dorsal motor nucleus (DMN), may cause anti-inflammatory effects in peripheral tissues. Vagal efferents originating in the brainstem and extending to peripheral organs, may help to reduce inflammation. Vagotomy, which inhibits the vagus nerve, may reveal directional alterations between the periphery and the CNS. Inhibiting vagal afferents with a vagotomy and administering inflammatory chemicals to the periphery suggest that at low doses, the vagal afferent nerves may be a primary mechanism for translating peripheral inflammation to central inflammation, affecting behavior such as sleep. Vagotomy cannot prevent central inflammation caused by peripheral inflammation as a result of high concentrations of inflammatory stimuli which suggests that the blood-brain barrier is ineffective and also involved in CNS inflammation.
In individuals with rheumatoid arthritis, vagal nerve stimulation is utilized as an alternate treatment to decrease TNF. Vagal nerve stimulation may help those with inflammatory bowel disease. The effects of this anti-inflammatory medication are due in part to the stimulation of cholinergic neurons, which causes peripheral inflammation to be suppressed, which subsequently reduces CNS inflammation. In fact, vagal nerve stimulation decreased daily drowsiness, improved tiredness, and lowered whole blood cell levels of TNF-, IFN-, IL-6, and IL-1 in people with Sjörgen’s syndrome.
Cerebral blood flow is a critical component in supplying nutrients and oxygen to cells in the central nervous system The neurovasculature also eliminates waste products like as carbon dioxide and signaling chemicals, as well as providing enough energy reserves. Cellular and performance problems may result from a decline in blood supply in a region around neurons in the CNS. Multiple sclerosis, type 1 diabetes, Alzheimer’s disease, and celiac disease are all linked to hypoperfusion. Neural activity is synchronized with localized cerebral blood flow, which is known as neurovascular coupling. Increases in the production of vasoactive chemicals are linked to increased brain activity, which may affect vascular hemodynamics directly or indirectly.
Sleep, and Autoimmune and Related Disorders Endothelial cells, smooth muscle, astrocytes, neurons, and pericytes make up the neurovascular unit at the level of the cerebral microvasculature, which includes arterioles and capillaries, and it is influenced by microglia and perivascular macrophages. Changes in metabolism and inflammation may also affect astrocyte end-feet, affecting cerebral blood flow (CBF). The neurovascular unit regulates blood flow throughout the brain and is influenced by the surrounding cells’ energy demands as well as the vasoconstrictive and vasodilative substances secreted by these cells, such as catecholamines and dopamine.
Monoamines released by neurons have both vasodilative and vasoconstrictive properties, which can influence blood flow. Pro-inflammatory molecules tend to be vasodilative, reduce vascular resistance, and increase cerebral CBF, whereas monoamines released by neurons have both vasodilative and vasoconstrictive properties, which can influence blood flow. Vasoconstrictive drugs usually raise vascular resistance and lower CBF.
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