• blood brain: barrier btwn blood & extracell fluid
  • endothelium
• blood csf: barrier btwn blood & csf
  • Epithelium (tight ependyma)
• csf brain: btwn csf & xc fluid
  • epithelium (leaky ependyma)
• neuronal: btwn xc fluid & intracell fluid
  • not diff from most other membranes

• leaky fenestrated, selectively permeable endoth
• Specialized endoth cells
  • NO pinocytotic vesicles, NO fenestration, NO tight jxns
• specialized transport molec,
• subarachnoid space

• Dura mater - bv = fenestrated endoth
• Arachnoid & Pia mater: BV = NO festestrations, No tight jxn
  • component of bbb

• Basil Lamina
  • thin bm supports abluminal surface. surrounds endoth cells & pericytes. astrocytes adjacent ot endoth cells share the basil lamina
  • components: laminin, fibronectin, tenascin, collagen, proteoglycans
  • fxn: cell attachment, migration, barirer to macromolec
• Pericytes
  • regulate endoth cell prolif, survival, migration, differentitation, branching
  • NO alpha actin so NO contraction. gap jxns conncet w/ endoth. PHAGOCYTIC
• Astrocytes
  • envelop 99% of bbb endothelia. intercell adhesion to endoth by both gap jxns & adherens jxn.
  • det bbb fxn, morph, prot expression. guide vessel growth by interacting cap & neurons

• large molecules
• low lipid soluble molec
• high electrically charged molec
• toxins/drugs

• multi component barrier
• physical: tight jxn (nonfenestrated) seal cell to cell contacts btwn adjacent cells
  • high electrical resistance barrier --> low paracellular perm
  • clefts btwn endoth cells so jxnal complex must constrict btwn cap endoth cells
  • diff to get thru elec barrier

• occludin
  • 65kD. brings opposing cell membranes into contact
  • reg prot: alter paracellular perm
• claudins
  • form dimers that bind homtypically to claudins on adjacent endoth cell
  • 22kD
  • 4 transmembrane domains, localized TJ strand
  • from primary seal for tight jxn
• zonula occludens
  • cytoplasmic proteins interact w/ occludin to act as recog prot for tight jxnal placement
  • number of sights for binding to cytoskel kinases & signal transduction prot
• juctional adhesion molcules (jam)
  • localized tight jxns- members
  • members of large Ig superfamily

• protection/reg cns
• Reg NT, ions, GF transfer from plasma to brain
• Reg dietary salt water movement
• barrier to passage of harmful substances
• Specialized features imp for fxn
  • Inc # & vol of mito: req for active transport thru BBB
  • enzymatic barrier: metab drugs & nutrients
  • dec in cap wall thickness: allow dec transport time
  • polarity btwn luminal & abluminal surfaces
    • luminal: Gamma-GT, alk phos, P-glycoprot efflux transporter
    • abluminal: Na-KAtpase, neutral aa transporter, Glut-1-R (3:1 ablum: lum)

• lipid mediation: passive
  • restricted to small lipid soluble products (drugs)
• catalyzed transport:
  
  • carrier mediated: facilitated & active trasport (FAST)
  • receptor mediated transporters: slow, mostly prots
• Transport Mechanisms
  • passive diffusion: most drugs - must be lipid soluble & unionized
  • facilitated: for CHO/AA metab subratres, carrier no ATP
  • active transport: ATP dep, vits ions
  • pinocytosis: brain cap lack sig pinocytotic vesicles, imperm to most macro molec

Blood-csf Barrier

-Choroid plexus

• fenestrated choroidal capillaries & tight jxns btwn choroidal epith
  • form & maintain CSF
  • potential leaky at base
  • small surface area
  • secretory & reabsorption fxn
    • organic acid/base pumps remove metab from csf back to c. plexus for venous drainage
• choroid plexus cells modified ependyma cells
  • line ventricular: keep csf from going back to the brain
• tufts of cap covered by cub epith cells
  • protrude into lumen of ventricles, secrete CSF
• location: lat, third & 4th ventricles

• leaky ependymal wall of ventricles
• allows free exchange btwn csf & brain interstitial fluid down conc graidents
  • interstitial fluid bathes brain proper
  • dense arrangement of neurons in brain limits free diffusion of most drugs from csf to brain approx 1-1.5cm
• circumventricular organs

• brain structures that req contact w/ peripheral blood for monitoring & normal fxn
• surface exposed to blood = fenestrated, surface exposed to brain around the ventricles = tight jxns
• area postrema/chemoreceptor triggor zone, pit gland, pineal gland, parts of hypothalamus
• SIGHTS WHERE BBB IS LACKIN
  • in contact w/ walls of ventricular system & lined w/ choroid plexus
  • fxnal interface btwn nervous & endocrine system
• subfornical organ, lamina terminalis, median eminence,pineal gland, area postrmea (in 4th ventricle)
  • modified cap: fenestrated endoth, free exchange btwn blood & ecf of brain - imp in distribution of hormones in blood

• from eyeballs to tip of spinal cord
• foramen magnum: end cranial dura, begin spinal dura
• Spaces
  • epidural
    • potential space btwn skull & dura
    • real space in spinal cord btwn dura & vertebral periosteum
  • subdural
    • potential space btwn dura & arachnoid
  • subarachnoid
    • csf filled space btwn arachnoid & pia
    • structural spearation by arachnoid trabeculae
• arachnoid = translucent Dura = bery thick, pia mater
  • from skull to brain: dura, arachnoid, pia

• epidural
  • tearing of meningeal artery or venous structure
  • BIG
• subdural
  
  • tearing of cerebral vein as it penetrates arachnoid & enters sinus

• NO cells
• clear & colorless
• lots of chloride, glc, some protein
• fxn
  • protects the cns from trauma
  • provide mechanical buoyancy & support for the brain
  • serves as a reservoir & assists in reg of contents of skull
  • nourish cns
  • removes metab from the cns
  • serves as path for pineal secreatons to reach pit gland

• filled w/ CSF
• Lateral Vent
  • one in each cerebral hemisphere
• third vent
  • midline cavity in diencephalon
  • communicates w/ the lat vent thru interventricular foramina
  • communicates w/ 4th vent thru cerebral aqueduct
• fourth vent
  • btwn cerebellum, pons, medulla

• lat vent --> interventricular foramen--> 3rd--> cerebral aqueduct --> 4th (median aperture) --> lat aperture --> ciserns (pontine & magna)
• cerebellum sits on top of 4th vent
• median aperture open from 4th vent straight to spinal cord so now get flow
• cisterns accum of csf

• villi
  • protrude into sinuses
  • layer of endoth & arachnoid only btwn venous blood
  • major sites of csf reabsorp into venous syst
  • one way flow from subarachnoid space to venous blood
    • csf thru large vacuoles in endoth cells
    • csf movement thru channels btwn cells
• granulations
  • groups of arachnoid villi
  • like grains of sand, csf from subarachnoid space to venous drainage
• one way valve

• constant flow btwn MABP of 60-150 mmHg, rang shifts up in HTN
• Inc Pco2- vasodialtion & inc flow
• Dec Pco2 - vasoconstrict & dec flow
• inc H+ (acidosis, dec neuronal active) vasodilate, inc flow
• Dec PO2 (ischemia): vasodil & inc flow
• INc PO2: vasoconstrict, dec flow
• as artierial PCo2 inc, cerebral blood flow inc

• Normal ICP = 65-150 mm H20 (5-15 mmhg)
• >20 mmHg = inc
• only 37% of pts w/ >40mmGh for 15 min have favorable outcomes
  • when ICP >90 = cerebral circ collapes

• uncus herniation
  • through tentorial notch & pressing on midbrain
  • sever effects = pappilledema
• tonsil herniation
  • through tonsil of cerebellum herniates thru foramen magna
  • compress medulla
• cingulate gyrus herniation
  • subdural hematoma

• CPP = MABP - ICP
  • as icp inc the cpp dec & correspondingly cerebral blood flow
  • vessels collapse when icp >MaBP
• sx inc icp: headache, papilledema, altered mental status, inc bp, dec HR
• cushing reflex
  • sign of inc icp
  • inc systolic bp, inc pulse pressure, & dec HR as ICP inc to fatal levesl

• vasogenic
  • inc perm BB, inc ECF
  • usu responsive to steroids & diuretics
• cytotoxic edema
  • hypoxia, failure of Na/K pump
  • inc intracell fluid/cell swell
  • cell filiure
• interstitial edema
  • inc edema/fluid in white matter around vent
  • usu assoc w/ hyroccephalus

• in head injury
  • hyperventilate via respirator for first 24hrs
• elevate head of bead to 30 degrees w/ pt in midline position
• maintain bp in normotensive range
  • high bp inc icp while low bp compromises cerebral blood flow