Lecture 16: Cerebrospinal fluid and Blood Brain Barrier Flashcards
what three structures help stabilize the neurons in the CNS
- BBB
- Choroid plexus
- CSF
___fluid in the brain is continuous with CSF
Interstitial fluid
What is the purpose of meninges
Cover and protect the CNS, protect blood vessels and enclose venous sinuses, contain CSF, source of growth factors
What are the three meninges
- Dura
- Arachnoid
- Pia mater
What is the dura mater
Outermost layer, two fibrous CT layers
What is the arachnoid mater
Middle me I’ve which forms a loose brain covering
What is the subarachnoid space
Space beneath the arachnoid that is filled with CSF and large blood vessels
What is the pia mater
Innermost layer composed of delicate CT that associates tightly to ependymal cells of the brain
Ventricles are filled with ___ and lined with ____ cells
CSF and lined with ependymal cells
What are the 4 ventricles in the brain
2 lateral ventricles, 3rd ventricle, 4th ventricle
Where is the third ventricle located
Level of thalamus
Where is the 4th ventricle located
Brain stem
What connects the ventricles
Aqueducts
What shape are the ependymal cells
Squamous to columnar
What do ependymal cells line
Brain surface, ventricles, and choroid plexus
What are the 3 functions of ependymal cells in the CNS
- Undergo cellular proliferation to serve as a source of stem cells for new neurons and glial cells in the brain
- Help produce CSF from blood plasma
- In ventricles, help form and circulate CSF
Disrupting the movement of __ can affect movement of CSF
Cilia
Describe the circulation of CSF
- Flows through the intraventricular foramina to 3rd ventricle
- 3rd ventricle flows through cerebral aqueduct to 4th ventricle
- CSF exits the 4th ventricle through the lateral and median apertures and enters subarachnoid space
- CSF flows through the subarachnoid space to the arachnoid granulations in the superior Sagittarius sinus where is enters venous circulation
Removal of CSF occurs primarily in the ___
Sagittal sinus
Where is the dorsal sagittal sinus located
Between two hemispheres
CSF is absorbed across the ___ into the venous circulation by drainage into lymphatic vessels
Arachnoid villi
Describe the pressure differences between the CSF and venous system
CSF pressure is greater than venous system and therefore makes a one-way flow of fluid out of the brain
What is hydrocephalus
Increased CSF volume in the skull associated with increased intracranial pressure
What is non-communicating hydrocephalus
Blockage of CSF movement through the cerebral aqueduct or the lateral or medial apertures
Non-communicating hydrocephalus is also known as
Internal hydrocephalus
Where does pressure increase in non-communicating hydrocephalus
Pressure increased internally and ventricles expand
What are some potential causes of non-communicating hydrocephalus
- Secondary to feline infectious peritonitis
- Congenital disorder
What is communicating hydrocephalus
Impairment of absorption into dorsal sagittal sinus
What is communicating hydrocephalus also known as
External hydrocephalus
Where is the blockage in communicating hydrocephalus
Arachnoid villi in the foramen of Luschka
Where does the pressure occur in communicating hydrocephalus
Outside of brain
What is a treatment option for hydrocephalus
Ventriculo-peritoneal shunt
What are some causes of hydrocephalus
- Congenital in brachycephalic toy breeds
- Inflammation of meninges
- Tetrogenic viruses during fetal development
- Brain stem tumors
- Vitamin A deficiency in calves and birds
- Plant toxins from Veracruz californium or astragalus
What are the two locations for a CSF tap
- Cisterns manga- subarachnoid space cranial to C1 and caudal to occipital bone
- Subarachnoid space in lumbar spine
Where do you collect CSF in lumbar spine
L5-6, or L6-7
What are the normal protein levels in cisternal tap
<35 mg/dL
What are the normal protein levels in the lumbar tap
<45-50 mg/dL
What are the glucose levels in the cisternal taps
60-80% BG
What are the glucose levels in lumbar tap
60-80% BG
What is the normal RBC in cisternal and lumbar taps
0 cells/uL
What is the normal WBC in cisternal tap
< 4 cells/uL
What is the normal WBC in lumbar tap
<8-10 cells/uL
Where is CSF located
Ventricles of brain and central canal of spinal cord
Where is CSF formed
Choroid plexus
CSF is absorbed in the sagittal sinus for venous return via the ___
Arachnoid villi
CSF and brain interstitial fluid are formed by…
Selective movement of solutes across the BBB
Compared to blood serum what are the K+ levels like in CSF
CSF has lower K+ levels
Does the CSF have more or less proteins than blood serum
Less
T or F: CSF and blood serum have similar osmolarity
True, otherwise there would be fluid imbalance
Why does the CSF facilitate movement of ions down concentration gradients
To facilitate uptake into the brain
what ions are influxed into the CSF
Na+, HCO3-, Cl-
Na+, HCO3- and Cl- create osmotic gradient by which ___ is taken into CSF
Water
What are the 4 components of the BBB
- Endothelial cells
- Tight junctions, adherence junctions, desmosomes
- Basement membrane
- Glia (astrocytes)
How does exchange occur at the BBB
Transport through endothelial cell channels
BBB is infective against what substances
Lipophilic substances like steroids, water, oxygen, carbon dioxide
Diffuse through plasma membrane
where is the BBB absent and why
Absent in vomiting centers and hypothalamus allowing the ability to monitor the chemical composition of blood and release hormones to the body
Brain capillaries interact with ___ and __ to selectively control movement of materials into the brain
Astrocytes and pericytes
What are the selective entry mechanisms through the BBB
- Diffusion of lipid soluble substances
- Receptor mediated transport
What two things function in BBB to remove or avoid entry of toxic substances
Metabolic barriers ad P-glycoprotein
What is the energy source for the brain during starvation, used in place of glucose
Ketone bodies
CO2 diffuses across the BBB and increases proton concentration, how does the body respond
Chemoreceptors in the brain will increase breathing to combat acidosis
What GLUT receptor is responsible for low level basal glucose uptake. Occurs in endothelial cells and astrocytes
GLUT1
What GLUT receptor is a high affinity isoform that is mainly present in neurons
GLUT3
What does P-gp/ MDR1 do
Removes large lipophilic molecules from the CSF
How does P-gp work
ATP driven efflux transporter pumps substrates out of the cells
Promotes elimination of drugs into bile and urine
What does the drug amitriptyline do
Temporarily inhibit the blood brain barrier
What are macrocylic lactones
Broad antiparasitic against larval nematodes and arthropods
What breed does ivermectin cause neurotoxicity in and why
Collies, mutation in MDR1 mutation so therefore ivermectin crosses BBB and is unable to be removed
Collies given 100-120mg/kg ivermectin will have what symptoms
Mydriasis, ataxia and depression
How does ivermectin work once it passes BBB in collies
Binds GABA gated Cl- channels, impairing GABA signaling