Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood–brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of these barrier properties are an important component of pathology and progression of different neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of the blood vessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease.
The blood–brain barrier (BBB) is a term used to describe the unique properties of the microvasculature of the central nervous system (CNS). CNS vessels are continuous nonfenestrated vessels, but also contain a series of additional properties that allow them to tightly regulate the movement of molecules, ions, and cells between the blood and the CNS. This heavily restricting barrier capacity allows BBB ECs to tightly regulate CNS homeostasis, which is critical to allow for proper neuronal function, as well as protect the CNS from toxins, pathogens, inflammation, injury, and disease. The restrictive nature of the BBB provides an obstacle for drug delivery to the CNS, and, thus, major efforts have been made to generate methods to modulate or bypass the BBB for delivery of therapeutics. Loss of some, or most, of these barrier properties during neurological diseases including stroke, multiple sclerosis (MS), brain traumas, and neurodegenerative disorders, is a major component of the pathology and progression of these diseases. BBB dysfunction can lead to ion dysregulation, altered signaling homeostasis, as well as the entry of immune cells and molecules into the CNS, processes that lead to neuronal dysfunction and degeneration.
www.ncbi.nlm.nih.gov
Sars-cov-2 and the BBB in Mice
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic. In addition to pneumonia and acute respiratory distress, COVID-19 is associated with a host of symptoms that relate to the CNS, including loss of taste and smell, headaches, twitching, seizures, confusion, vision impairment, nerve pain, dizziness, impaired consciousness, nausea and vomiting, hemiplegia, ataxia, stroke and cerebral hemorrhage. It has been postulated that some of the symptoms of COVID-19 may be due to direct actions of the virus on the CNS; for example, respiratory symptoms could be in part due to SARS-CoV-2 invading the respiratory centers of the brain. Encephalitis has also been reported in COVID-19, and could be a result of virus or viral proteins having entered the brain. SARS-CoV-2 mRNA has been recovered from the cerebrospinal fluid, suggesting it can cross the blood–brain barrier (BBB). Other coronaviruses, including the closely related SARS virus that caused the 2003–2004 outbreak, are able to cross the BBB and SARS-CoV-2 can infect neurons in a BrainSphere model. However, SARS-CoV-2 could induce changes in the CNS without directly crossing the BBB, as COVID-19 is associated with a cytokine storm, and many cytokines cross the BBB to affect CNS function.
A 2021 study assesses whether one viral protein of SARS-CoV-2, the spike 1 protein (S1), can cross the BBB. This question is important and clinically relevant for two reasons. First, some proteins shed from viruses have been shown to cross the BBB, inducing neuroinflammation and otherwise impairing CNS functions. Second, the viral protein that binds to cells can be used to model the activity of the virus; in other words, if the viral binding protein crosses the BBB, it is likely that protein enables the virus to cross the BBB as well. S1 is the binding protein for SARS-CoV-2; it binds to angiotensin-converting enzyme 2 (ACE2) and probably other proteins as well.
The 2021 study shows that I-S1 readily crossed the murine BBB, entered the parenchymal tissue of the brain and, to a lesser degree, was sequestered by brain endothelial cells and associated with the brain capillary glycocalyx. It describes I-S1 rate of entry into the brain after intravenous (i.v.) and intranasal administration, determine its uptake in 11 different brain regions, examine the effect of inflammation, APOE genotype and sex on I-S1 transport, and compare I-S1 uptake in the brain to the uptake in the liver, kidney, spleen and lung. Based on experiments with the glycoprotein WGA, the study found that brain entry of I-S1 likely involves the vesicular-dependent mechanism of adsorptive transcytosis.
www.nature.com
pubmed.ncbi.nlm.nih.gov
My take away question for further research;
If you intake something that creates the S1 spike proteins, does it mean you would actively compromise your CNS and to what extent would it be compromised besides the most obvious effects on the senses?
@Luther12 what are your thoughts on these studies?
The blood–brain barrier (BBB) is a term used to describe the unique properties of the microvasculature of the central nervous system (CNS). CNS vessels are continuous nonfenestrated vessels, but also contain a series of additional properties that allow them to tightly regulate the movement of molecules, ions, and cells between the blood and the CNS. This heavily restricting barrier capacity allows BBB ECs to tightly regulate CNS homeostasis, which is critical to allow for proper neuronal function, as well as protect the CNS from toxins, pathogens, inflammation, injury, and disease. The restrictive nature of the BBB provides an obstacle for drug delivery to the CNS, and, thus, major efforts have been made to generate methods to modulate or bypass the BBB for delivery of therapeutics. Loss of some, or most, of these barrier properties during neurological diseases including stroke, multiple sclerosis (MS), brain traumas, and neurodegenerative disorders, is a major component of the pathology and progression of these diseases. BBB dysfunction can lead to ion dysregulation, altered signaling homeostasis, as well as the entry of immune cells and molecules into the CNS, processes that lead to neuronal dysfunction and degeneration.
The Blood–Brain Barrier
Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood–brain barrier, which ...
Sars-cov-2 and the BBB in Mice
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic. In addition to pneumonia and acute respiratory distress, COVID-19 is associated with a host of symptoms that relate to the CNS, including loss of taste and smell, headaches, twitching, seizures, confusion, vision impairment, nerve pain, dizziness, impaired consciousness, nausea and vomiting, hemiplegia, ataxia, stroke and cerebral hemorrhage. It has been postulated that some of the symptoms of COVID-19 may be due to direct actions of the virus on the CNS; for example, respiratory symptoms could be in part due to SARS-CoV-2 invading the respiratory centers of the brain. Encephalitis has also been reported in COVID-19, and could be a result of virus or viral proteins having entered the brain. SARS-CoV-2 mRNA has been recovered from the cerebrospinal fluid, suggesting it can cross the blood–brain barrier (BBB). Other coronaviruses, including the closely related SARS virus that caused the 2003–2004 outbreak, are able to cross the BBB and SARS-CoV-2 can infect neurons in a BrainSphere model. However, SARS-CoV-2 could induce changes in the CNS without directly crossing the BBB, as COVID-19 is associated with a cytokine storm, and many cytokines cross the BBB to affect CNS function.
A 2021 study assesses whether one viral protein of SARS-CoV-2, the spike 1 protein (S1), can cross the BBB. This question is important and clinically relevant for two reasons. First, some proteins shed from viruses have been shown to cross the BBB, inducing neuroinflammation and otherwise impairing CNS functions. Second, the viral protein that binds to cells can be used to model the activity of the virus; in other words, if the viral binding protein crosses the BBB, it is likely that protein enables the virus to cross the BBB as well. S1 is the binding protein for SARS-CoV-2; it binds to angiotensin-converting enzyme 2 (ACE2) and probably other proteins as well.
The 2021 study shows that I-S1 readily crossed the murine BBB, entered the parenchymal tissue of the brain and, to a lesser degree, was sequestered by brain endothelial cells and associated with the brain capillary glycocalyx. It describes I-S1 rate of entry into the brain after intravenous (i.v.) and intranasal administration, determine its uptake in 11 different brain regions, examine the effect of inflammation, APOE genotype and sex on I-S1 transport, and compare I-S1 uptake in the brain to the uptake in the liver, kidney, spleen and lung. Based on experiments with the glycoprotein WGA, the study found that brain entry of I-S1 likely involves the vesicular-dependent mechanism of adsorptive transcytosis.
The S1 protein of SARS-CoV-2 crosses the blood–brain barrier in mice - Nature Neuroscience
Rhea at al. show that intravenously injected, radiolabeled SARS-CoV-2 spike 1 protein crosses the mouse blood–brain barrier, likely through the mechanism of adsorptive transcytosis and is also taken up by peripheral tissues.
www.nature.com
The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice - PubMed
It is unclear whether severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019, can enter the brain. Severe acute respiratory syndrome coronavirus 2 binds to cells via the S1 subunit of its spike protein. We show that intravenously injected radioiodinated S1 (I-S1)...
My take away question for further research;
If you intake something that creates the S1 spike proteins, does it mean you would actively compromise your CNS and to what extent would it be compromised besides the most obvious effects on the senses?
@Luther12 what are your thoughts on these studies?
if you grow patient enough to actually read such studies, you will gain basic ideas about why patients lose some senses.
