3b Blood-Brain Barrier

brain, liver, GI tract

most energy expensive organs in the human body

lungs, GI system

since the brain does not have significant capacity to store metabolic nutrients, fuel to power the brain is provided on-demand by the _____ and _____ _______

vascular

the ______ system is crucial in delivering nutrients necessary to maintain normal brain function

neuronal death

interruption of cerebral blood flow quickly leads to _______ _____

immediately, 5

in cardiac arrest, neuronal apotosis begins almost ______; brain damage occurs after about ___ minutes

homeostasis, neurovascular unit

blood-brain barrier regulates ________ of the CNS by forming a tightly regulated __________ _____ (NVU)

endothelial cells, pericytes, astrocytic endfeet

what is included in the NVU?

neurotoxic plasma components, blood cells, pathogens

the BBB prevents what from entering the brain?

leakage, infiltration, clearance, blood flow, neurological

BBB breakdown and dysfunction leads to __________ of harmful blood components into CNS, cellular ____________, aberrant transport and ___________ of molecules, cerebral __________ _________ reductions, ______________ deficits

1. endothelium of parenchymal microvessels
2. epithelium of choroid plexus secreting CSF
3. arachnoid epithelium

barrier layers found at 3 main sites in brain and spinal cord...

choroid plexus

modified ependymal lining of brain ventricles

arachnoid epithelium

middle layer of meninges forming outer covering of CNS

circumventricular organs (CVOs)

regions of the brain with a "leaky endothelium" allowing relatively free access between blood and neural tissue

neurosecretory brain areas, such as the posterior pituitary gland

where are CVOs usually

endothelial, tight

The BBB proper barrier is created at level of cerebral capillary ___________ cells by __________ junction formation

blood-CSF barrier

lies at choroid plexuses in ventricles of the brain

arachnoid barrier

at arachnoid villi that are CSF drainage sites

toxins, ion homeostasis,

The BBB controls molecular traffic, keeps out ___________ (preserves neural connectivity) and contributes to ________ ___________ for optimal neural signaling

protein, proliferation, connectivity

The BBB maintains low-___________ environment in CNS; limits ___________, preserves neural _____________

neurotransmitter, cross-talk, non-synaptic

The BBB separates central and peripheral _____________ pools, reduces ___________, and allows ____________ signaling in CNS

immune, inflammation, damage

The BBB allows ____________ surveillance and response with minimal ____________ and cell __________

cerebral endothelial cells

key cells of BBB connected by tight junctions to restrict paracellular transport into the brain

pericytes

partially envelop endothelial cells

astrocyte endfeet

ensheath microvessels' wall

barrier induction, maintenance, neurons

pericytes and astrocytes are important in _______ _____ and _______; astrocytes mediate the connection to _______

vasculature, nervous system

the brain endothelium forming the BBB and blood-spinal cord barrier is the largest interface between the _____ and _______ ____

diffusion distance

BBB has shortest ______ _____ to neurons

the pattern of cerebral blood vessels follows the major brain circuits of the brain

why is it important that the BBB has the shortest diffusion distance?

20, 20

under physiological conditions, the human brain receives ___% of the cardiac output and uses ___% of the body's oxygen and glucose

neurovascular coupling

cerebral blood vessels supplying the CNS circuits in response to neuronal stimuli by increasing the rate of cerebral blood flow and oxygen delivery

physical, transport, enzymatic, immunological

the BBB serves as a ______, ______, _____, and ______ barrier

cross

leukocytes may ____ the BBB adjacent to, or by modifying tight junctions

passively diffuse, greater

solutes may _____ _____ through the cell membrane and cross the endothelium; ________ lipid solubility favors this process

active efflux carriers

_______ _______ ____ may intercept some of these passively penetrating solutes and pump them out of the endothelial cell

carrier-mediated influx

may be passive or secondarily active, can transport many essential polar molecules such as glucose, AA, and nucleosides into the CNS

receptor mediated transcytosis (RMT)

transport macromolecules such as peptides and proteins across the cerebral endothelium

adsorptive mediated transcytosis (AMT)

induced non-specifically by positively charged macromolecules

surface, intracellular

tight junction modulation occurs by _________ and ____________ enzymes

immune

the BBB is strengthened by the _______ system as early as in embryonic development

TJ proteins

maternal gut microbiota influences the formation of fetal BBB during gestation by upregulating expression of ______ ________ such as claudin-5

increases

BBB permeability ________ in systemic inflammation, infection, autoimmune disease, injuries, and neurodegenerative diseases

pro-inflammatory cytokiines and chemokines, peripheral leukocytes (monocytes), and macrophages enter the brain and exacerbate diseases

why does BBB permeability increase in these scenarios?

true

t/f: some viruses can directly infect the endothelial cells of the human BBB

proteins, transporters

Endothelial cells get infected by targeting junctional ___________ such as JAM-A or ______________ such as GLUT1 as entry receptors to get access to the CNS

downregulate, chemokine, BBB

Endothelial cells get infected because viral infections ____________ TJ proteins and promote ____________ production and VCAM-1 expression in the brain endothelial cells, weakening the _________ and allowing entry into the brain

host immune response

The _________ ___________ __________ limits the spreading of the viruses and attenuates BBB damage

BBB proper, blood-CSF barrier, arachnoid barrier

what are the three barriers in the CNS?

endothelial cells, pericytes, astrocytes

which cells form the NVU?

physical, transport, enzymatic and immunological barrier

What are the four main functions of the BBB?

cell migration, passive diffusion, active efflux, active influx, RMT, AMT, TJ modulation

What are the six main ways for transportation through the BBB?

increased cerebral blood flow in response to neuronal activity

cerebrovascular coupling