Blood brain barrier

Question 1

BBB consist of
1. _____________ cells lining the capillary wall with _______ _____ between them
2. _______________ of astrocytes abutting on the capillaries as perivascular end-feet.
3.a _________ basement membrane
4.__________

Answer 1

1. ENDOTHELIAL cells lining the capillary wall with TIGHT JUNCTIONS between them
2. PROCESSES of astrocytes abutting on the capillaries as perivascular end-feet.
   3.a CAPILLARY basement membrane
   4.PERICYTES

Question 2

The function of ________________ (BBB) is specialized system of brain _____________ endothelial cell (BMVEC) that shields the brain from __________ substances in the blood, _______ brain tissues with _________, and ________ harmful compounds from the brain back to the bloodstream.

Answer 2

The blood-brain barrier (BBB) is the specialized system of brain microvascular endothelial cells (BMVEC) that shields the brain from toxic substances in the blood, supplies brain tissues with nutrients, and filters harmful compounds from the brain back to the bloodstream.

Question 3

Proportions of the blood-brain barrier
1.____________and ___________
2.
Note that _______ with a diameter of ________nm
Other components of the _______________ unit are indicated.

Answer 3

Proportions of the blood-brain barrier
1.capillary lumen and walls
2. basement membrane
Note that albumin with a diameter of 7 nm
Other components of the neurovascular unit are indicated.

Question 4

BBB- Nuerovascular Unit consist of :
1.
2.
.3
.4.
5.
6.
7.
8.

Answer 4

BBB- Nuerovascular Unit consist of :
1. Endothelial cell
2.Pericyte
3. Astrocyte End feet
4. Interneuron
5. Neuron
6. Astrocyte
7.Basement membrane
8. Microglia

Question 5

Confocal image shows elements of the neurovascular unit in the ____________. An _______ consisting of ___________-,_______________ and modified _______________ cell layers is surrounded by _____________ processes. Some of the ____________ processes in the surrounding __________ are in close proximity to the ____________ astrocytes and the vessel wall.

Answer 5

Confocal image shows elements of the neurovascular unit in the cerebral cortex. An arteriole consisting of endothelial, smooth muscle, and modified leptomeningeal cell layers is surrounded by astrocytic processes (red). Some of the
neuronal processes (green) in the surrounding neuropil are in close proximity to the perivascular astrocytes and the vessel wall.

Question 6

Anatomy of the BBB
1.
2.
3.
4.
5.
6.
7.

Answer 6

1. Neuron
2. Basal lamina
3. Endothelial cell
4. Lumen
5. Tight junction
   6.Pericyte
   7.Astrocyte feet

Question 7

The ________________ (BM) is a sheet-like (ECM) extracellular matrix complex ___________ epithelium and endothelium.

Answer 7

The basement membrane (BM) is a sheet-like (ECM) extracellular matrix complex beneath epithelium and endothelium.

Question 8

At the BBB the BM encircles the ______________ side of the ____________ and is located at the interface of the circulation system and central nervous system.

Answer 8

At the BBB, the BM encircles the abluminal side of blood vessels and is located at the interface of the circulation system and central nervous system.

Question 9

Brain BM consists of 5 major proteins:
1.
2.
3.
4.
5.

Answer 9

1.collagen IV*
2. laminin
3. nidogen
4. perlecan*
5. agrin*****

Question 10

_________________________ have many properties which are similar to those present in _______________________ including the expression of ___________________, ___________ molecules and __________ receptors.

Answer 10

Brain endothelial cells have many properties which are similar to those present in nonneural endothelium including the expression of glycoproteins, adhesion molecules, and integrin receptors.

Question 11

The principal morphological features which distinguish the endothelial cells of _______________ vessels from those of ____________ vessels and form the structural basis of the BBB to proteins include reduced density of _______________ and the presence of circumferential _______________ between endothelial cells.

Answer 11

The principal morphological features which distinguish the endothelial cells of intracerebral vessels from those of nonneural vessels and form the structural basis of the BBB to proteins include reduced density of caveolae and the presence of circumferential tight junctions between endothelial cells.

Question 12

Brain endothelial cells also have increased density of ____________________.

Answer 12

Brain endothelial cells also have increased density of mitochondria.

Question 13

A wide range of ____________________ molecules can diffuse through the endothelium and enter brain ______________.

Answer 13

A wide range of lipid-soluble molecules can diffuse through the endothelium and enter brain passively.

Question 14

_________, which carry a positive charge, have an advantage over __________ in penetration of endothelial cells and it is probably the cationic nature of these molecules and an interaction with the negatively charged_________________ and phospholipid head groups of the outer leaflet of the cell membrane that facilitates their entry.

Answer 14

Bases, which carry a positive charge, have an advantage over acids in penetration of endothelial cells and it is probably the cationic nature of these molecules and an interaction with the negatively charged glycocalyx and phospholipid head groups of the outer leaflet of the cell membrane that facilitates their entry.

Question 15

____________________ ___________________ transport across cerebral endothelium occurs by:
1.
2.
3.
4.
5.

Answer 15

Transcellular bidirectional transport across cerebral endothelium occurs by:
1. receptor-mediated transport
2.carrier-mediated transport
3. ion transport
4.peptide transport
5. active efflux transport.

Question 16

____________ transport systems facilitate transport of nutrients into brain including:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.

Answer 16

Carrier-mediated transport systems facilitate transport of nutrients into brain including:
hexoses (glucose, galactose)
neutral, basic and acidic amino acids
monocarboxylic acids (lactate, pyruvate, ketone bodies) nucleosides
(adenosine, guanosine, uridine)
purines (adenine, guanine)
nucleotides
nucleobases
organic anion, and organic cations
amine
vitamins.

Question 17

Endothelial cells tight junctions:
1 CELL:
1. Claudins (pegada al terminal ___ y _____ intracelular)+ _________
2.Occludin (pegada al terminal ____ y _____ intracelular)+ ________
3. JAMs (pegada al terminal _____ y el _____ se encuentra + extraceullar) + ___________

2 CELL:
1.En el terminal ____ esta pegado ZO-___ (L-cingulin y R-actin)
2. En el terminal _____ esta pegado ZO-___ (actin) y en el ________ esta MUPP1, parece estar pegado también con ZO-_____.
3.En el terminal ______ esta ZO-____ (actin) pegado con MAGIs.

Answer 17

1 CELL:
1. Claudins (pegada al terminal N y C intracelular)+ apicales
2.Occludin (pegada al terminal C y N intracelular)+ medial
3. JAMs (pegada al terminal C y el N se encuentra + extraceullar) + basal

2 CELL:
1.En el terminal C esta pegado ZO-1 (L-cingulin y R-actin)
2. En el terminal C esta pegado ZO-2 (actin) y en el N esta MUPP1, parece estar pegado también con ZO-2.
3.En el terminal C esta ZO-3 (actin) pegado con MAGIs

Question 18

CLAUDIN MONOMER

Answer 18

Is compose of TM1, TM2, TM3, TM4 bonded by EL1 AND EL2.

In the Paracellular space:
EL1is the bond (paracellular ion selectivity)
TM1 + TM2 are bonded maybe by S-S (Still unknown)
Is HCV entry (Claudin-1,-6,-9)

Citosol:
Terminal of TM1 finish w. NH2.
Terminal of TM2 continues to TM3 and connects to it. (Palmitoylation)

In the Paracellular space:
TM3 + TM4 are bonded by EL2 which is doing Oligomerization (CPE binding (Claudin -3,-4).

Citosol:
TM3 docent have a terminal
In TM4 terminal is occurring phosphorylation and finishes with COOH (PDZ- interacting domain)

Question 19

Endothelial junctions

___________ are present at the apical end of the _______-endothelial space being intimately connected to.

Are dependent on the ___________ based adherens junctions which are located near the _______side of the _______endothelial space.

Answer 19

Endothelial junctions

Tight junctions are present at the apical end of the interendothelial space being intimately connected to

Are dependent on the cadherin based adherens junctions which are located near the basolateral side of the interendothelial space.

Question 20

Ultrastructural studies of the tight junctions of brain endothelial cells demonstrate close approximation of the _____________ leaflets of adjacent plasma membranes forming a __________________ structure, which prevents the passage of tracers such as ________________ peroxidase (HRP) into the brain.

Answer 20

Ultrastructural studies of the tight junctions of brain endothelial cells demonstrate close approximation of the outer leaflets of adjacent plasma membranes forming a pentalaminar structure, which prevents the passage of tracers such as horseradish peroxidase (HRP) into the brain.

Question 21

These tight junctions extend circumferentially around the endothelial cells forming a barrier to __________________passage of small _________________ molecules such as
1.
2.
3.
4.
A property referred to as its “______ OR _________” function.

Answer 21

These tight junctions extend circumferentially around the endothelial cells forming a barrier to paracellular passage of small hydrophilic molecules such:
1. as sodium,
2.hydrogen,
3.bicarbonate, .
3. and other ions
A property referred to as its “gate or barrier” function.

Question 22

Tight junctions also _______________ the movement of membrane molecules between the functionally distinct apical and basolateral membrane surfaces, a property referred to as its “__________” function.

Answer 22

Tight junctions also restrict the movement of membrane molecules between the functionally distinct apical and basolateral membrane surfaces, a property referred to as its “fence” function.

Question 23

Freeze-fracture studies demonstrate that the tight junctions of cerebral endothelium consist of __-____parallel strands having no discontinuities, which run along the longitudinal axis of the vessel, with numerous lateral anastomotic strands.

Answer 23

Freeze-fracture studies demonstrate that the tight junctions of cerebral endothelium consist of 8–12 parallel strands having no discontinuities, which run along the longitudinal axis of the vessel, with numerous lateral anastomotic strands

Question 24

Claudin family

The claudin family consists of _______members in mice and humans and exhibit distinct expression patterns in tissue and cells.

Claudins are 18–27-kDa __________ proteins with a short cytoplasmic N-terminus, two extracellular loops, and a COOH terminal cytoplasmic domain which ends in valine.

Claudins are considered to be the main structural components of ____________________ strands and recruit occludin to tight junctions.

Claudin-______ regulates size-selective diffusion of small molecules since claudin-_________ knockout mice show _______________ paracellular permeability to molecules <800D.

Answer 24

The claudin family consists of 24 members in mice and humans and exhibit distinct expression patterns in tissue and cells.

Claudins are 18–27-kDa tetraspan proteins with a short cytoplasmic N-terminus, two extracellular loops, and a COOH terminal cytoplasmic domain which ends in valine.

Claudins are considered to be the main structural components of intramembrane strands and recruit occludin to tight junctions.

Claudin-5 regulates size-selective diffusion of small molecules since claudin-5 knockout mice show increased paracellular permeability to molecules <800D.

Question 25

Localization and structure

Tight junctions are localized at ______________________-enriched regions along the plasma membrane associated with Cav-1.

Research using a variety of cell types including cerebral endothelial cells demonstrates that tight junctions are composed of an intricate combination of _____________ and ________________ transmembrane and cytoplasmic proteins linked to an _______-based cytoskeleton that allows these junctions to seal the paracellular space while remaining capable of rapid modulation and regulation.

The ______ tetraspan transmembrane proteins are the claudin family of proteins and __________, while the single-span transmembrane protein is the junction adhesion molecule (______) family of proteins.

The ___________________ proteins form the paracellular permeability barrier and determine the capacity and the selectivity of the paracellular diffusion pathway.

Answer 25

Localization and structure

Tight junctions are localized at cholesterol-enriched regions along the plasma membrane associated with Cav-1.

Research using a variety of cell types including cerebral endothelial cells demonstrates that tight junctions are composed of an intricate combination of tetraspan and single-span transmembrane and cytoplasmic proteins linked to an actin-based cytoskeleton that allows these junctions to seal the paracellular space while remaining capable of rapid modulation and regulation.

The two tetraspan transmembrane proteins are the claudin family of proteins and occludin, while the single-span transmembrane protein is the junction adhesion molecule (JAM) family of proteins.

The tetraspan proteins form the paracellular permeability barrier and determine the capacity and the selectivity of the paracellular diffusion pathway.

Question 26

Occludin

Occludin, a ______ kDa protein, participates in forming and maintaining the barrier between adjacent cells and acts as a _______ to restrict movement of lipids and proteins between the apical and lateral domains. Occludin is present in most occluding junctions.

However, several types of epithelial cells do not have occludin within their strands but still possess well-developed and fully functional ___________ occludentes.

Occludin is a _____________ protein, associated with the ________membrane strands at tight junctions, although it is NOT required for their assembly.

Occludin knockout mice are still capable of forming interendothelial tight junctions having ___________ morphology and barrier function in intestinal epithelial cells, while ____________ knockout mice are nonviable (Osp/claudin-11 null mice).

Answer 26

Occludin

Occludin, a 60 kDa protein, participates in forming and maintaining the barrier between adjacent cells and acts as a fence to restrict movement of lipids and proteins between the apical and lateral domains. Occludin is present in most occluding junctions.

However, several types of epithelial cells do not have occludin within their strands but still possess well-developed and fully functional zonulae occludentes.

Occludin is a regulatory protein, associated with the intramembrane strands at tight junctions, although it is not required for their assembly.

Occludin knockout mice are still capable of forming interendothelial tight junctions having normal morphology and barrier function in intestinal epithelial cells, while claudin knockout mice are nonviable (Osp/claudin-11 null mice).

Question 27

JAM and PDZ

Junctional adhesion molecule (______) is a ________ kDa protein that belongs to the immunoglobulin superfamily (IgSF).

JAM does not itself form a zonula occludens strand but is instead associated with ___________. It is responsible for _________________ the electrical resistance of the cell membrane, thereby reducing paracellular permeability.

JAM is involved in the formation of _____________ junctions in endothelial cells as well as between endothelial cells and _______________ migrating from the vascular space to the connective tissue.

Overexpression of JAMs in cells that do not normally form tight junctions ______________ their resistance to the diffusion of soluble tracers, suggesting that JAM functionally contributes to ________________control

PDZ-domain proteins- ____________ occludens proteins ZO-____, ZO-______, and ZO-_______.

______________functions during the formation of the zonula occludens have been suggested for all ZO proteins.

In addition, ZO-1 is a _____________, and ZO-2 is required in the epidermal ________________–receptor signaling mechanism.

The ZO-3 protein interacts with ZO-1 and the cytoplasmic domain of _____________.

Answer 27

Junctional adhesion molecule (JAM) is a 40 kDa protein that belongs to the immunoglobulin superfamily (IgSF).

JAM does not itself form a zonula occludens strand but is instead associated with claudins. It is responsible for increasing the electrical resistance of the cell membrane, thereby reducing paracellular permeability.

JAM is involved in the formation of occluding junctions in endothelial cells as well as between endothelial cells and monocytes migrating from the vascular space to the connective tissue.

Overexpression of JAMs in cells that do not normally form tight junctions increases their resistance to the diffusion of soluble tracers, suggesting that JAM functionally contributes to permeability control

PDZ-domain proteins- zonula occludens proteins ZO-1, ZO-2, and ZO-3

Regulatory functions during the formation of the zonula occludens have been suggested for all ZO proteins.

In addition, ZO-1 is a tumor suppressor, and ZO-2 is required in the epidermal growth factor–receptor signaling mechanism.

The ZO-3 protein interacts with ZO-1 and the cytoplasmic domain of occludins.

Question 28

What technique is used to measure paracellular transport?

Answer 28

SUCROSE (C-14)
EVANS BLUE ( HYPEROSMOTIC PERMEABILITY STRATEGIES)

Question 29

______________influence on the brain water content in male and female Sprague Dawley rats

Answer 29

NG291

Question 30

MIGROGLIA

Immune role in _____
Maintain central homeostasis
Combat disease: __________________ role
(microglia>phagocytic macrophages)
________________ (promote axonal growth and migration)
Comprise ___-____% of total glia cells in adult
Contain ________________receptors
Important feature: _______________

M____- resting -> surveillance function + healthy DA-neuron

M_____-Inflammatory marker —> (iNOS) -> pro inflammatory -> neurotoxic function

M_____- Anti-inflammatory marker —–> Arginase I (Arg1)–> anti-inflammatory –> neuroprotective function

Answer 30

Immune role in CNS
Maintain central homeostasis
Combat disease: neuroprotective role
(microglia>phagocytic macrophages)
Development (promote axonal growth and migration)
Comprise 10-20% of total glia cells in adult
Contain neurotransmitter receptors
Important feature: polarization

M0- resting -> surveillance function + healthy DA-neuron

M1-Inflammatory marker —> (iNOS) -> pro inflammatory -> neurotoxic function

M2- Anti-inflammatory marker —–> Arginase I (Arg1)–> anti-inflammatory –> neuroprotective function

Question 31

Caveolae

Present in different type of cells.
They are flask-shaped membrane-bound vesicles having a mean diameter of ~70 nm which can open to both the luminal and abluminal plasm.

Intracerebral cortical vessels contain a mean of 5 caveolae/mm2 in arteriolar and capillary endothelium a membrane through a neck 10–40 nm in diameter.

Cerebral endothelium contains 14-fold fewer vesicles as compared with endothelium of nonneural vessels such as myocardial capillaries.

The decreased number of vesicles in cerebral endothelium implies limited transcellular traffic of solutes in steady states.

In contrast, capillaries in areas where a BBB is absent such as the subfornicial organ and area postrema, are highly permeable and have significantly higher numbers of endothelial caveolae.

Answer 31

Caveolae

Present in different type of cells.

They are _______-shaped membrane-bound vesicles having a mean diameter of ~______ nm which can open to both the luminal and abluminal plasm.

Intracerebral cortical vessels contain a mean of ______ caveolae/mm2 in arteriolar and capillary endothelium a membrane through a neck 10–40 nm in diameter.

Cerebral endothelium contains ______-fold fewer vesicles as compared with endothelium of nonneural vessels such as ______________ capillaries.

The _____________ number of vesicles in cerebral endothelium implies____________ transcellular traffic of solutes in steady states.

In contrast, capillaries in areas where a BBB is absent such as the subfornicial organ and area postrema, are _________ permeable and have significantly ______________numbers of endothelial caveolae.

Question 32

Several lines of research implicate ________________- in the process of vesicular trafficking in
1. transcytosis of proteins
2. endocytosis
3. and potocytosis.

Both endocytosis and transcytosis may be receptor-mediated or fluid phase and require _______ and can be inhibited by _________________(NEM), an inhibitor of membrane fusion.

__________________ regulate a wide variety of signaling molecules.

In addition, caveolae function in the ____________of cell:
1.cholesterol and glycosylphosphatidylinositol (GPI)-linked proteins
2. in cell migration: as docking sites for glycolipids
3. flow sensors.

Endothelial ________________ are involved in endocytosis, a process by which the permeant molecules are internalized within endothelial cells or they may be involved in transfer of molecules from blood across the cell to the interstitial fluid or in the reverse direction, a process termed ___________________.

Answer 32

Several lines of research implicate caveolae in the process of vesicular trafficking in transcytosis of proteins, endocytosis, and potocytosis.

Both endocytosis and transcytosis may be receptor-mediated or fluid phase and require ATP and can be inhibited by N-ethylmaleimide (NEM), an inhibitor of membrane fusion.

Caveolae regulate a wide variety of signaling molecules.

In addition, caveolae function in the regulation of cell cholesterol and glycosylphosphatidylinositol (GPI)-linked proteins, in cell migration, as docking sites for glycolipids and as flow sensors.

Endothelial caveolae are involved in endocytosis, a process by which the permeant molecules are internalized within endothelial cells or they may be involved in transfer of molecules from blood across the cell to the interstitial fluid or in the reverse direction, a process termed transcytosis.

Question 33

It is generally accepted that caveolae is a _____________.

The caveolae _________________is enriched in b-d-galactosyl and b-N-acetylglucosaminyl residues in palmitoleic and stearic acids and in cholesterol and sphingolipids (sphingomyelin and glycosphingolipid).

The sphingolipids are substrates for synthesis of a second intracellular messenger, the __________________.

Cholesterol provides a _____________________ support for caveolae and creates the frame in which many caveolar molecules are inserted.

Located in the _________ of caveolae are the caveolin (Cav) family of proteins, which comprise three members named Cav-____, ______, and _______.

In brain, Cav-______ and ________ are primarily expressed in endothelial cells, while Cav-____ is expressed in astrocytes.

Answer 33

It is generally accepted that caveolae is a lipid raft.

The caveolae membrane is enriched in b-d-galactosyl and b-N-acetylglucosaminyl residues in palmitoleic and stearic acids and in cholesterol and sphingolipids (sphingomyelin and glycosphingolipid).

The sphingolipids are substrates for synthesis of a second intracellular messenger, the ceramides.

Cholesterol provides a structural support for caveolae and creates the frame in which many caveolar molecules are inserted.

Located in the coat of caveolae are the caveolin (Cav) family of proteins, which comprise three members named Cav-1, 2, and 3.

In brain, Cav-1 and 2 are primarily expressed in endothelial cells, while Cav-3 is expressed in astrocytes.

Question 34

Cav-_____, the specific marker and major component of caveolae, is an integral membrane protein (_____–____kDa) having both amino and carboxyl ends exposed on the cytoplasmic aspect of the membrane (30).

The two major isoforms of Cav-_______ are ______(alpha) and _______(beta) and brain cells express predominantly the _______-isoform.

Answer 34

Cav-1, the specific marker and major component of caveolae, is an integral membrane protein (21–24 kDa) having both amino and carboxyl ends exposed on the cytoplasmic aspect of the membrane (30).

The two major isoforms of Cav-1 are alpha (a) and beta (B)and brain cells express predominantly the a -isoform.

Question 35

A segment of arteriolar endothelium from a control rat shows caveolae © in the endothelial and smooth muscle cells. Many of the caveolae show electron-dense deposits representing_______+-________ localization.

Answer 35

A segment of arteriolar endothelium from a control rat shows caveolae © in the endothelial and smooth muscle cells. Many of the caveolae show electron-dense deposits representing Ca2+-ATPase localization. X 84, 000.

Question 35

______________________ is a multistep process that involves:
1. successive caveolae budding and fission from the plasma membrane
2. translocation across the cell
3. followed by docking and fusion with the opposite plasma membrane.

_____________ contain the molecular machinery for these processes:
1. vesicle-associated membrane protein-2 (VAMP-2) 2.monomeric and trimeric GTPases
3.annexins II and IV
4.N-ethyl maleimide (NEF)
5.sensitive fusion factor (NSF) and its attachment protein
6.soluble NSF attachment protein (SNAP)
7. vesicle-associated SNAP receptor (v-SNARE).

Answer 35

Transcytosis is a multistep process that involves:
1. successive caveolae budding and fission from the plasma membrane
2. translocation across the cell
3. followed by docking and fusion with the opposite plasma membrane.

Caveolae contain the molecular machinery for these processes:
1. vesicle-associated membrane protein-2 (VAMP-2) 2.monomeric and trimeric GTPases
3.annexins II and IV
4.N-ethyl maleimide (NEF)
5.sensitive fusion factor (NSF) and its attachment protein
6.soluble NSF attachment protein (SNAP)
7. vesicle-associated SNAP receptor (v-SNARE).

Question 36

Receptors present in ______________membranes are involved in:
receptor-mediated transcytosis of low- and high-density lipoprotein
epidermal growth factor
tumor necrosis factor
albumin
transferrin
melanotransferrin
lactoferrin
ceruloplasmin
transcobalamin
advance glycation
products
leptin
insulin

all of which are essential in maintaining cell and tissue homeostasis and are therefore referred to as the _______ receptors.

Also present are _________ receptors which are involved in cell apoptosis and include receptors for ______ and interleukin-____.

Answer 36

Receptors present in caveolae membranes are involved in:

receptor-mediated transcytosis of low- and high-density lipoprotein
epidermal growth factor
tumor necrosis factor
albumin
transferrin
melanotransferrin
lactoferrin
ceruloplasmin
transcobalamin
advance glycation
products
leptin
insulin

all of which are essential in maintaining cell and tissue homeostasis and are therefore referred to as the LIFE receptors.

Also present are DEATH receptors which are involved in cell apoptosis and include receptors for p75 and interleukin-1.

Question 37

Active __________ transport involves a transporter, which utilizes _____________ to shuttle drugs and other solutes _________ of the brain and ___________ the blood compartment.

___________ transporters ________________ effective drug penetration into brain parenchyma, thus limiting the efficacy of drugs targeted at brain diseases.

Verapamil is a _______________.

Answer 37

Active efflux transport involves a transporter, which utilizes ATP to shuttle drugs and other solutes out of the brain and into the blood compartment.

Efflux transporters minimize effective drug penetration into brain parenchyma, thus limiting the efficacy of
drugs targeted at brain diseases.

Verapamil is a substrate.

Question 38

_______________________lack the BBB.

Structures locate in the ____________ of
the ventricular system.

Participate in biochemical signaling and cell exchange between the ________ and the __________ (ex. hormonal control).

___________________ tight junctions between endothelial cells allow entry of molecules

Answer 38

Circumventricular Organs lack the BBB.

Structures locate in the midline of
the ventricular system.

Participate in biochemical signaling and cell exchange between the brain and the blood (ex. hormonal control).

Discontinuous tight junctions between endothelial cells allow entry of molecules

Question 38

Strategies to Facilitate the Delivery of Therapeutic Agents Across the Barriers

__________________ DIFFUSION

__________________________
- Hyperosmotic agents
-Ultrasound

________________ PATHWAY

Transcytosis of lipid molecules
Transportes mediated pathway
Adsorptive transcytosis
Receptor-mediated pathway
Inhibiton of efflux transporter

__________________
- Lipidization
-Targeting moieties attachment

____________________
-Nanoparticles
-Cells

Answer 38

Strategies to Facilitate the Delivery of Therapeutic Agents Across the Barriers

PARACELLULAR DIFFUSION

Disruption of BBB
- Hyperosmotic agents
-Ultrasound

TRANSCELLULAR PATHWAY

Transcytosis of lipid molecules
Transportes mediated pathway
Adsorptive transcytosis
Receptor-mediated pathway
Inhibiton of efflux transporter

Drug modification
- Lipidization
-Targeting moieties attachment

Carrier-based delivery
-Nanoparticles
-Cells

Question 38

Technique to measure transcytosis?

Answer 38

Albumin (Tc-Albumin)

Question 39

1. ________________ - water soluble agents
2. _________________- lipid-soluble agents (eg. antidepressants, nicoten, alcohol)
   3._________________ -glucose, amino acids, nucleosides, vinca alkaloids, cyclosporine A, gabapentin
   4._______________________ - insulin, transferrin, interleukins
   5._____________________- albumin, other plasma membrane
   6._________________- cetirizine

Answer 39

1. Paracellular transport - water soluble agents
2. Diffusion- lipid-soluble agents (eg. antidepressants, nicoten, alcohol)
   3.Protein Transporters -glucose, amino acids, nucleosides, vinca alkaloids, cyclosporine A, gabapentin
   4.Receptor-mediates transcytosis - insulin, transferrin, interleukins
   5.Adsortive transcytosis- albumin, other plasma membrane
   6.Efflux transporters- cetirizine

Question 40

TMD1- consist of 6 units (1-6)
intracellular has in unit 1 N2H + and unit 6 connected to NBD1 (ATP production)

TMD2 - consists of 6 units (7-12)
intracellular has in unit 7 connected to NBD1 + unit 12 connected to NBD2 (ATP production) with COOH bonded at its terminal.

Answer 40

___________- consist of 6 units (_______)
intracellular has in unit 1 N2H + and unit 6 connected to NBD____ (ATP production)

__________ - consists of 6 units (___________)
intracellular has in unit 7 connected to NBD1 + unit 12 connected to NBD__ (ATP production) with ___________ bonded at its terminal.

Question 41

Strategies for brain delivery

Answer 41

viral vectors

nanoparticles

exosomes

delivery through active
transporters in the BBB

brain permeability enhancer

delivery through the permeable BBB under disease conditions

non-envase techniques to enhance brain drug uptake

alteration of administration routes

Nanoparticles for brain imaging/diagnostics

Question 42

Astrocyte end-feet ________________ blood vessels in the brain and are believed to provide structural integrity to the cerebral vasculature.

Answer 42

Astrocyte end-feet ensheate blood vessels in the brain and are believed to provide structural integrity to the cerebral vasculature.