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Table 6 Overview of efflux routes showing clearance values for substances leaving the brain parenchyma from ISF

From: Elimination of substances from the brain parenchyma: efflux via perivascular pathways and via the blood–brain barrier

Substances Features Clearance/µL g−1 min−1
Passive, non-specific transfer across the blood–brain barrier
 H2Oa, CO b2 , O c2 , NH c3 Very small molecules 1000–7000a, > 6500 largeb
 Methanol, ethanol, antipyrine, isopropanol Highly lipid soluble moleculesd > 100
 Glycerol, ethylene glycol, butyric acid Moderately lipid solubled 100 > CL > 10
Transfer across the blood–brain barrier by specific transporters
 Glucosee Via GLUT1 50–100
 Lactatef Via MCT1 60–100
 Many substratesg Via Slc22 and Slco transporters 11–364
 Amino acidsh Via L, A, ASC, N, y+, EAAT and others Seeh
 K+i Via several routes including the Na+ pump and NKCC1i 11.3
Efflux via blood–brain barrier and perivascular fluxes
 Amyloid-βk Primarily across blood–brain barrier ~10k
 Na+ j, Cl− j mannitoll Via both blood–brain barrier and perivascular routes c. 1–2
Efflux via perivascular routes only
 Sucrose, inulin, albumin, larger dextrans and PEGsm Used as markers for perivascular efflux c. 1
  1. Values substantially greater than ~ 1 µL g−1 min−1 imply that clearance is primarily across the blood–brain barrier rather than via perivascular efflux
  2. aSee Sect. 5.1
  3. bSee Sect. 5.2
  4. cClearance known to be large but difficult to measure
  5. dSee Fig. 8
  6. eSee Sect. 5.3 and Appendix D
  7. fSee Sect. 5.4
  8. gSee Table 1
  9. hNet fluxes at blood–brain barrier 1–20 nmol g−1 min−1, perivascular effluxes (except glutamine) ~ 0.1 nmol g−1 min−1, glutamine ~ 1 nmol g−1 min−1
  10. iSee Appendix E, NKCC1 is the Na+, K+, 2Cl—cotransporter; jsee Appendix E
  11. kSee Sect. 5.7.3
  12. lSee Appendix B
  13. mNegligible blood–brain barrier clearance, see Sect. 3 and Appendix B