Ventricles, CSF, Cerebral blood flow, and BBB

Anencephaly

-*Failure of Anterior Neuropore to Close* >Leaking CSF due to open system -Anencephaly leads to FAILURE of forebrain development -Result is stillbirth or death within 24 hours after birth. -Seen in ultrasound *Open neuropore*

Congenital Hydrocephalus

Present at Birth -EXCESS CSF production and over- dilation of ventricles -One of the most common birth defects (1/500 births) -Severely disrupts neurogenesis and brain development

Physiological regulation of CSF Formation

REDUCTION by: -Sympathetic innervation -Certain neurotransmitters

Communicating Hydrocephalus

Occurs when flow of CSF is BLOCKED after it exits the ventricles -CSF can still flow between ventricles, hence the name "Communicating"

Choroid Epithelium: Apical Membrane

*Extrusion of Na+ into CSF is the primary step* -*Na/K-ATPase* actively PUMPS sodium into the ventricles (Active transporter) >Inhibited by *Ouabain* ->Na+ would increased inside of the cell and concentration gradient would decrease -Na+/K+/2Cl- Cotransporter translocates Cl- down electrochemical gradient. >Reversible Transporter >Inhibited by *bumetanide or furosemide* -K+-Cl- cotransport, K+-channels, and Cl-channels also contribute to net directional ion fluxes.

CSF

*Cerebrospinal Fluid* -Cell free fluid that fills ventricular system of the CNS produced by choroid plexus -Flows from areas of 3rd/4th ventricles to the spinal cord -Drains through *arachnoid granulations/villi* into *Superior Sagittal Sinus* -CSF volume in an adults is 150mL

Choroid Blood Supply

Lateral ventricles: -Anterior Choroidal Artery (Branch of MCA from internal carotid artery) -Posterior choroidal artery (Branch of PCA) 3rd ventricles: Posterior cerebral artery 4th ventricles: Cerebellar arteries

Circle of Willis (Pathway)

Major Arteries of the brain arise from the Circle of Willis. -Anterior Cerebral Artery -Middle Cerebral Artery -Posterior Cerebral Artery -Anastomosis of internal carotid and vertebral arteries forms the Circle of Willis.

CSF formation: Neurotransmitters

May act DIRECTLY on epithelial cells to REDUCE CSF secretion -May also CONSTRICT *choroidal blood arterioles* thereby DECREASING capillary pressure and INDIRECTLY affecting the rate of CSF production

CSF Pressure

Measured directly by *lumbar puncture*: Needle to get to fluid space -10-15 mmHg in prone position -CSF Pressure varies with: >Systolic pulse wave >Respiratory cycle >Abdominal pressure >Jugular venous pressure >State of arousal >Physical activity >Posture

Embryonic development of ventricles

Neural plate develops and *completes neurulation* to form neural tube (4th Week) -Ends of neural tube, neuropores, close >Brain: Anterior Portion >Spinal Cord: Posterior Portion -Segmentation, Bending and Expansion result in >Forebrain (F): Splits into two Lateral Ventricles and the Third Ventricle >Midbrain (M): Becomes Cerebral Aqueduct >Hindbrain (H): Becomes Fourth Ventricle which is the first to develop/secrete CSF

Normal Pressure Hydrocephalus

Occurs in patients ≥60 years old -Gradual onset of some occlusion and constant OUTFLOW of CSF -Ventricles slowly expand: Pressure rise but not as high >Not typical symptoms like other hydrocephalus conditions -Complains: Shuffle when walk, legs give up, memory loss, high urine flow, etc -Neuronal death is occurring and usually misdiagnosed as Alzheimer's disease >Hard to treat due to loss in nervous system.

Schematic representation of the microvascular unit of the cerebral circulation

Pial arteries are seen

Astrocyte Neuron-Lactate Shuttle (Pathway)

Picture: Transport of glucose across the blood brain barrier and lactate production by the astrocyte. --- Glutamate formed in presynaptic terminal from glutamine-> presynaptic terminal -> effect on postsynaptic -Excess glutamate is degraded or majority will leak out of the synaptic cleft going away from receptors and be taken up by the astrocyte-> that glutamate is metabolized to glutamine-> goes back to pre-synaptic terminus -Astrocytes provide a route where they provide substrate for metabolism (lactate) which is important for energy production >Important role of removing excess glutamate and moving it way from the cleft and then later re-make glutamate -Some glucose goes across the IF which can be used by the neurons

Choroid Plexuses of the brain

*4 choroid plexuses of the brain* Area of BVs covered by epithelial cell layer -Locations -Temporal horn of each Lateral Ventricle (2) -Posterior portion of Third Ventricle (1) -Roof of Fourth Ventricle (1)

Increased shear stress on endothelial surface causes

*Activation of TRP channel and Calcium mobilization* SMALL conductance K+ channels (SK) and intermediate conductance (IK) K+ channels are ACTIVATED on the endothelial cell allowing K+ efflux from endothelial cells -Arachidonic acid metabolites are also released from the endothelial cells -K+ activation HYPERPOLARIZES the endothelial cell -Hyperpolarization wave spread from endothelial cell to smooth muscle cell via myendothelial gap junctions (MEGJ). -Smooth muscle *relaxation and dilation of blood vessel*

Excess CO2 and H+ Result in...

*INCREASED cerebral blood flow* -Blood Flow (Q) through the Internal Carotid and Vertebral Arteries INCREASES as the arterial CO2 content of the blood INCREASES -Mechanism of dilation appears to be mediated through *H+* *Vasodilation rises in proportion to [H+] up to maximum flow limit* CO2 + H2O (Carbonic Anhydrase)-> H2CO3-> H+ + HCO3

Third Ventricle

*In diencephalon*

Astrocytes and Endothelial cells in cerebral blood flow

*Involved in regulation of cerebral blood flow* -*Glutaminergic Neurons* ACTIVATE receptors on astrocytes that lead to INCREASED intracellular calcium -Ca2+ leads to opening of potassium channels on astrocyte foot process through direct and indirect via *arachinonic acid (AA) metabolites* (Prostaglandins, prostacyclins, etc) -*BK channels* open allowing K+ efflux from astrocyte -Vascular smooth muscle potassium channels (Kir) open -*Hyperpolarization* of the vascular smooth muscle cell leads to DECREASED VSM cytosolic Ca2+ -Smooth muscle RELAXATION, and DILATION of the blood vessel

Non-Communicating Hydrocephalus

*Obstructive hydrocephalus* -Occurs when the flow of CSF is blocked along one or more of the narrow passages connecting the ventricles -*Aquaductal Stenosis*: NARROWING of Aquaduct of Sylvius >MRI: Dilated 3rd and 4th ventricle; 4th ventricle will look normal/smaller -Can do surgery and put a shunt there preventing expansion of ventricles which may press on brain tissue and cause swelling. >Flow goes to abdomen (peritoneal cavity) so can be absorbed to systemic circulation

Circulation of CSF

*Produced by Choroid Plexus* -Lateral Ventricle CSF flows to Third Ventricle via *Foramen of Monro* -CSF from Third Ventricle enters Fourth Ventricle via *Cerebral Aqueduct* (Aqueduct of Sylvius) -CSF from Fourth Ventricle enters *Subarachnoid Space* via several foramina (*foramen of Magendie*) -CSF fills *subarachoid space* around the brain and spinal cord (contains most of the CSF) -CSF enters *Superior Sagittal Sinus* via *Arachnoid Villi/Granulations* -Fluid in Superior Sagittal Sinus returns to the *Venous Circulation*

Cerebral Blood Flow Autoregulation

*Protects Against Arterial Pressure Fluctuations* -Brain blood flow remains relatively CONSTANT over a wide range of arterial pressures *60-140 mmHg* >Under 60mmHg, will see big drop in flow -Autoreguated vascular bed -Sympathetic nerves only play a minor role

Schizencephaly

*Slit or cleft in brain tissue* allows CSF to LEAK OUT of the ventricular system -Results in NUMEROUS neurological problems Seizures >Developmental delays >Language difficulties >Motor deficit >Death -Gap in anterior region leading to CSF leakage *Open brain ventricle*

CSF Formation: Sympathetic innervation

*Sympathetic Innervation of Choroid Plexus from Superior Cervical Ganglion* -Norepinephrine DECREASES CSF formation -Most likely due to decreased Na+/K+ ATPase activity

Cushing Response

*Systemic Pressor Response to rising intracranial pressure that occurs in an effort to maintain cerebral blood flow.*

Choroid Epithelium: Basolateral Membrane

*Uptake of Na+ and Cl- is the primary step* -Na+-H+ exchanger transfers Na+ INTO choroid cell (passive antiporter) >Inhibited by *Amiloride* ->Drug would causes intracellular Na+ to deplete as the apical membrane would pump Na+ out -Cl-HCO3- >Sodium DEPENDENT process-> uses energy from Na+/H+ exchange >With amiloride effect, then this pump is indirectly affected

CSF Turnover Rate

- CSF renewed 4-5 times/day in young adults -CSF turnover is ~3 times/day in geriatric patients (≥80 yrs old). -Aging is associated with REDUCTION in brain parenchyma and EXPANSION of CSF compartment. >Expansion of ventricles occur but reduction of cerebral mass-> choroid still makes CSF but turnover decreases

Brain Blood Supply

-Blood supply is via *internal carotid and vertebral arteries.* -ICA and VA become tortuous which creates TURBULENT flow conditions -Internal Carotid and vertebral arteries anastomose to form Circle of Willis -Main intracerebral arteries branch off of the Circle of Willis. -Cerebral arteries are very sensitive to changes in blood gases and richly INNERVATED by branches of the cranial nerves. -The microvascular unit begins on the *pial surface* -Arteriolar diameter is sensitive to changes in perfusion pressure (CPP), arterial Oxygen (PaO2) and Carbon Dioxide (PaCO2), oxygen content (CaO2) and Hydrogen ion concentration -Venous drainage is via the sinuses which drain into the internal jugular and vertebral veins.

Cushioning of the Brain by CSF

-Brain and CSF have approximate equal specific gravities >Brain has slight higher specific gravity than H2) -Brain essentially FLOATS in CSF -Brain gets injured via penetrating wound or non penetrating traumatic injury >Increasing ICP could produce hernia-> brain thru foramen magnum

Fluid compartments of the brain (Diagram)

-CSF (blue arrows) is primarily produced by the *choroid plexus*. -The Blood CSF Barrier (BCSFB) is comprised of the *fenestrated capillaries* of the choroid circulation and the choroid plexus epithelial cells. -CSF returns to the circulation via the *arachnoid granulations* of the superior saggital sinus (SSS). -The Blood Brain Barrier (BBB) separates the continuous capillaries that supply the brain from the interstitial spaces.

Cerebral Blood flow during mild to moderate exercise

-Cerebral Blood flow INCREASES are primarily reflective of cortical activation and a SMALL increase in arterial CO2 -*Metabolic demand overrides pressure autoregulation*

Arachnoid Granulations

-Choroid plexus produces more CSF than body needs -Arachnoid granulations will help drain the CSF into venous circulation via superior sagittal sinus (SSS). -Lymph nodes can also help with CSF removal

Brain edema/swelling: Hydrocephalus

-Communicating -Non-Communicating -Idiopathic Normal Pressure Hydrocephalus

Blood Brain Barrier

-Continuous Capillaries of the brain restrict exchange of macromolecules across the capillary wall. >*Tight junctions* account for the restrictive nature -*Astrocyte foot process* surround the capillary endothelium: Come in contact/close proximity to endothelial cell of the capillary -Macromolecular exchange across the cerebral capillary wall

eCSF

-Differs in composition from adult CSF in that it *eCSF is protein rich* -eCSF important in mediating neuroepithelial *growth, proliferation, and neurogenesis* -eCSF secretion promotes *distention and expansion* by increasing pressure in the in the developing ventricular system.

Embryonic events: CSF formation

-Embryonic events leading to normal CSF formation of cerebral ventricles -Brain ventricle abnormalities resulting from disruption of normal processes. (Panel B).

Mechanism of CSF Formation

-Formation of CSF involves the net transfer of Na+, K+, Cl-, HCO3-, and water from plasma to the lumen of the cerebral ventricles. -Electrochemical gradients on the basolateral membrane of the choroidal epithelium favor Na+ entry into the epithelial cytoplasm and extrusion of HCO3-, K+, and Cl- into the CSF (DOWNHILL electrochemical gradients for the ions) -Net movement of flux and electrochemical gradient driving ions and water movement occurs ACROSS the choroid epithelial cell to the CSF

Astrocyte Neuron-Lactate Shuttle

-Glucose transported across capillary wall into the interstitial space >Taken up by Astrocyte and presynaptic neuron -Glucose metabolized by astrocyte >*Lactate* exits astrocyte and taken up by presynaptic neuron -Glucose and Lactate metabolism in presynaptic neuron results in *ATP formation* -Glutamine taken up by presynaptic terminus used in glutamate synthesis >*Glutamate* released as neurotransmitter -Residual *Glutamate* in synaptic cleft taken up by astrocyte >Metabolized to glutamine

Brain swelling (symptoms)

-Headache -Neck pain or stiffness -Nausea or vomiting -Dizziness -Irregular breathing -Vision loss or changes -Memory loss -Motor impairment -Speech impairment -Stupor -Seizures

Cushing Response (Triad of signs)

-Hypertension -Bradycardia -Apnea

Choroid Epithelium: Carbonic Anhydrase

-Not a transporter -Catalyzes formation of bicarbonate (HCO3-) from CO2 and H2O -HCO3- important in ion transport processes *Inhibited by acetazolamide*

BCSFB (Electron micrograph)

-Note that the capillaries are surrounded by an epithelial cell layer that SEPARATES the ventricular lumen from the interstitial spaces. -Fenestrated capillaries allow some material to move through >Fluid into ventricular lumen is not passive movement

Acquired hydrocephalus

-Occurs AFTER birth once the brain tissue has formed: normal brain/ventricle development -Possible Causes: >CSF OVERproduction >REDUCED CSF Absorption >ABNORMAL brain shape

Clinical Management Goal is to Preserve Blood Flow and Tissue Oxygenation

-Oxygen Therapy -Hyper-Oncotic IV Fluids -Hypothermia -Phamacological Management -Ventriculostomy -Surgery

Pathways Across the Blood Brain Barrier

-Paracellular: Small water soluble agents can potentially pass thru; remember tight junctions are present-> won't find a lot of movement thru this route b.) Transcellular (lipophilic): Molecules move by diffusing THRU lipid bilayer and diffuse thru endothelial layer thru IF surrounding the brain cells c.) Transport proteins: Their is actual receptors that bind and allow it to enter (glucose, alkaloids, AZT, cyclopsporins, etc) d.) Receptor mediated transcytosis: Receptor complex is endocytosed and then transferred to the other membrane where it enter IF (transport process) e.) Adsorptive transcytosis: Albumin, etc -BBB deals with molecules that have to move thru endothelial cells-> NOT rapid movement of most substances across cerebral vasculature

Pial arteries and microvasculature of brain

-Pial arteries course along the surface of the and give rise to penetrating arteries and arterioles. -*Virchow -Robin Space*: an extension of the subarachnoid space surrounds the penetrating vessels. -Capillaries arise from *intracerebral arterioles* -*Astrocytes* surround capillaries and form connections with other astrocytes as well as neurons (provides supporting role).

Cerebrospinal Fluid Formation

-Primarily secreted by *Choroid Plexus* >Total Volume in brain is ~150 ml >Total Volume Secreted per Day is ~500 ml

CSF (Functions)

-Protection of brain >Brain floats in "CSF pool" -Nutrient, drug, etc transport -Waste REMOVAL

Adult CSF

-Secreted primarily by choroid epithelial cells. -Contains only TRACE amounts of protein

CSF vs serum composition

-Sodium: About the same -Potassium: Lower in CSF -Chloride: Higher in CSF (wants to flow out of cell) -Calcium: Lower -Magnesium: Higher -pH: Similar -Protein: LOWER >Ventricular: Lowest as not much protein present in adult CSF and diluted with CSF >Higher in lumbar region: Less CSF and will be more concentrated with protein -Glucose: Lower

Common Causes of Brain Edema and Swelling

-Traumatic Brain Injury (TBI): Ischemic Strokes -Intracerebral Hemorrhage -Infections -Subdural Empyema -Tumors -High Altitude -Hydrocephalus >Communicating >Non-Communicating >Idiopathic Normal Pressure

Cerebral Blood Flow

-Two Pairs of Large Arteries -Internal Carotid Arteries > ~70% of total cerebral blood supply -Vertebral Arteries >~30% of total cerebral blood supply -Venules and CSF drain into sinuses which return blood back to the systemic circulation primarily via the *internal jugular vein*

Brain Edema and swelling (types)

-Vasogenic edema -Cytotoxic edema -Hydrocephalus

Lateral Ventricles

2: 1 Left and 1 right -Fluid leaves from the lateral ventricles through a paired interventricular foramina called *foramina of Monro* into the third ventricle -In the *cerebrum/telencephalon*

Hydrocephalus

A condition in which fluid accumulates in the brain, typically in young children, ENLARGING the head and sometimes causing brain damage -Too much made or cannot be excreted leading to disruption in brain development or function -Congenital -Acquired -Normal pressure hydrocephalus -Communicating or non-communicating

Cerebral Aqueduct

AKA Aqueduct of Sylvius Connects *Third Ventricle with Fourth Ventricle*. From the *mesencephalon*

Cerebral Blood Flow Regulation

Approximately 15% of the Cardiac Output is directed to the Brain -50-900 ml/min >50-65 ml/min/100g tissue Amount of blood flow to brain is tightly coupled with *metabolic activity* -Metabolic factors: >Carbon dioxide concentration >Hydrogen ion concentration >Oxygen concentration >Substances released by astrocytes

BBB (Cellular basis)

Astrocytes get to close proximity to endothelial cells -Arrangement allows movement of molecules across the capillary wall->Astrocyte has contact with neurons without creating huge big changes in IF concentration

Effects of Brain Activity on Regional Blood Flow (Graph)

Blood flow to the occipital lobe increases when light is shined into the eyes of a cat

Brain Blood Flow (Summary)

Brain blood flow as a function of exercise intensity -The cerebral blood flow response to exercise results from the integration of neurovascular coupling, cerebral vasoreactivity, and cerebral autoregulation

Vasogenic Edema

Caused by *breakdown of Blood Brain Barrier* >Examples include traumatic brain injury, tumors, abscesses, etc.

Cytotoxic Edema

Caused by metabolic poisoning, hypoxia or anoxia, and ischemia Capillaries becoming leakier-> swelling of CNS cells -> damage and death of neurons -Rarely responsive to hyperoncotic therapy -Neuronal processes impacted because you are in hypoxic situation

Cerebral blood flow during intense (heavy) exercise

Cerebral Blood flow RETURNS towards baseline because ventilation REDUCES arterial CO2 -*Autoregulation* becomes a predominate regulator. -Brain oxygenation is compromised as a result of normalization of blood flow during intense exercise -REDUCED cerebral oxygenation contributes to FATIGUE

Brain fluid compartments

Cerebrospinal Fluid -Separated from vascular compartment by *Blood CSF Barrier (BCSFB)* Interstitial Fluid >Separated from vascular compartment by *Blood Brain Barrier (BBB)*

Adult brain ventricles

Choroid plexus is showed in red

Non-penetrating traumatic brain injury

Coup vs noncoup injury -Sudden *deceleration* caused by the forehead hitting a fixed object can result in the frontal regions of the brain striking the skull (*Coup Injury*). >Head stops from it, brain floats and runs into the anterior cranial space -Subsequent bouncing back of the brain results in injury to posterior region of the brain (*Contrecoup Injury*) >Bounces back to occipital portion *A coup (same side) injury occurs under the site of impact with an object, and a contrecoup injury occurs on the side opposite the area that was hit*

Brain edema consequences

Cranial Vault limits outward swelling and results in compression of brain and associated vasculature-> Vascular compression decreases blood flow and causes brain ischemia-> Ischemia causes arteriolar dilation-> Arteriolar dilation produces further increases in capillary pressure-> Capillary filtration increases-> Edema WORSENS Cranial Vault limits outward swelling and results in compression of brain and associated vasculature-> Hypoxia increases capillary permeability and turns off neuronal sodium pumps-> Increases capillary filtration-> Neuronal cell swelling

Hydrocephalus (General)

Enlarged cranium as a result of *increased CSF pressure* -CSF overproduced or inadequately removed

Arachnoid Granulations (Absorption)

Finger-like endothelium lined protrusions of *arachnoid outer layer* into the lumen of the cranial venous sinuses -Function as *ONE way valves*: CSF removed by pressure gradient -CSF Pressure is 3-5 mmHg HIGHER than Superior Saggital Sinus (SSS) Pressure >SSS drains into the venous system. -In man, spinal arachnoid villi in the lumbosacral region of the spinal column account for a SMALL amount of CSF reabsorption. >CSF absorbed by the spinal arachnoid villi is returned to the circulation via the lymphatic system. -A very small amount of CSF is absorbed by the *olfactory mucosa* and cranial nerve sheaths of *Cranial nerve II, V, VII and VIII*. >CSF absorbed by this route enters the lymphatic system (minor). Picture: Cranial arachnoid granulations

Oil-Water Partition Coefficient Correlates with Brain Uptake of Many Compounds

Generally, compounds with higher coefficients (high oil/low water) have GREATER uptake. -Agents that bind to plasma proteins (e.g., *phenytoin and phenobarbital*) have LOWER uptake than predicted from partition coefficient alone.

Areas not covered by BBB

HIGHLY vascularized region without the BBB --- *Circumventriculate Organs* -Area Postrema: "Chemotatic Trigger Zone", "Vomiting Center" >Detects Toxins in Blood (vomit reflex) -Subfornical Organ and Organum Vasculosum >Osmoreceptors -Posterior Pituitary >Oxytocin >Antidiuretic Hormone (Vasopressin) -Pineal Body >Melatonin >Neuroactive Peptides -Median Eminence >Neurohormones

Other transporters located on the choroid epithelium

IMPORTANT for exchange of essential substances for cells in the CNS including: -Glucose -Amino Acids -Vitamins -Trace metals -Hormones -LOW concentrations of these substances contribute very LITTLE to the osmotic pressure of the CSF and exert LITTLE influence on the rate of CSF formation -Gap junctions help get into cell. -Specific transport processes are involved in the movement of a variety of other substances into the CSF.

MRI example

Images obtained from subjects showing ACTIVATION of discrete areas of the brain in response to *specific activity* -Shows what is happening at specific regions of the brain -Visual-> stimulates the occipital lobe

Fourth Ventricle

In the Brainstem -Lies between pons and cerebellum

Ventricular Systems of the brain

Interconnected fluid filled spaces (CSF) that lie in the core of the forebrain and brainstem -Lateral ventricles -Third ventricle -Fourth ventricle

Brain and oxygen tension

Reductions in Oxygen Tension INCREASES Cerebral Blood Flow -Decreases in brain PO2 *below 30 mmHg* INCREASES blood flow. -Protective mechanism since neuronal function disrupted at low PO2 (such as ≤20 mmHg-> hypoxia)

Increase in PaCO2 and brain flow rate (Graph)

Relationship between arterial CO2 content and blood flow in the major arteries supplying the brain *CO2 elevates, then flow in brain increases*

Oil-Water Partition Coefficient Graph

Relationship between oil-water partitition coefficient and brain uptake of compounds -Small water soluble molecules (low oil/water coefficient) have LOWER uptake rates than highly lipid soluble substances (Low extraction) -Small lipid soluble molecules (high oil/water coefficient) generally have HIGHER uptake rates (High extraction) -Binding of highly lipid soluble substances to *plasma proteins* can IMPAIR extraction. Outliers: -Glucose: Water soluble but has higher extraction rate as it contains *protein transporters* that allow it to cross BBB. -Phenytoin/Phenobarbital: High oil/water partition but relative extraction is LOW >Deviated from the line-> binds to albumin which impairs extraction

Steps of early embryonic brain morphogenesis (Steps)

Representation of early brain development. -Closing of the neuropores, segmentation, and secretion of CSF results in *increased pressure* that facilitates RAPID EXPANSION of the ventricles -CSF secretions begins when neuropores close

Choroid Plexus

SECRETES most of the cerebrospinal fluid into the ventricles -Secretes about 500mL CSF/day

Early embryonic brain ventricles vs adult brain ventricles.

Schematic comparison of embryonic and adult brain ventricles. -Lateral and third ventricles develop from forebrain regions. -Cerebral aqueduct develops from midbrain region -Fourth ventricle develops from hindbrain region.

CSF Formation (Picture)

Schematic depiction of the CSF formation, circulation, and absorption processes.

Choroid plexus (lateral ventricle slide)

Schematic representation of choroid plexus of lateral ventricle -Tight junctions between the epithelial cells

Cerebrospinal Fluid Absorption

The majority of CSF is absorbed by *cranial arachnoid granulations* and enters the *internal jugular system*

BCSFB and Brain-CSF interface

Top Panel: Capillaries in the *Choroid Plexus* are fenestrated capillaries that allow macromolecular exchange between the plasma and interstitial fluid. -Tight Junctions between epithelial cells PREVENT macromolecular diffusion into the CSF Bottom Panel: Epithelial cells of the ependymal layer have gap junctions between them. -The ependymal lining is permits relatively FREE DIFFUSION of solutes betweent the CSF and Brain interstitial fluid. >Allows bacteria, toxins, cancerous cells, etc to pass through >Epyndmal cells: Epithelial cells linking the ventricular system.

Blood supply of the spinal cord

Vertebral arteries give off branches that merge into the anterior spinal artery -Segmental arteries join the anterior spinal artery along its course-> also known as medullary arteries -Vertebral arteries/PICA give rise to paired posterior spinal arteries that run along the dorsal surface of the spinal cord.

Functional magnetic resonance imaging

fMRI method of INDIRECTLY assessing cerebral activity based on the principal that blood flow increases as brain activity INCREASES -Based on observation that oxyhemoglobin and deoxyhemoglobin behave differently in a magnetic field. -*Oxyhemoglobin* is REPELLED by magnetic field (*diamagnetic*) -*Deoxyhemoglobin* is ATTRACTED by a magnetic field (*paramagnetic*). *Indirectly assessing the cerebral activity*