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

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

Substances	Features	Clearance/µL g⁻¹ min⁻¹
Passive, non-specific transfer across the blood–brain barrier
H₂O^a, CO ^b₂ , O ^c₂ , NH ^c₃	Very small molecules	1000–7000^a, > 6500 large^b
Methanol, ethanol, antipyrine, isopropanol	Highly lipid soluble molecules^d	> 100
Glycerol, ethylene glycol, butyric acid	Moderately lipid soluble^d	100 > CL > 10
Transfer across the blood–brain barrier by specific transporters
Glucose^e	Via GLUT1	50–100
Lactate^f	Via MCT1	60–100
Many substrates^g	Via Slc22 and Slco transporters	11–364
Amino acids^h	Via L, A, ASC, N, y⁺, EAAT and others	See^h
K⁺ⁱ	Via several routes including the Na⁺ pump and NKCC1ⁱ	11.3
Efflux via blood–brain barrier and perivascular fluxes
Amyloid-β^k	Primarily across blood–brain barrier	~10^k
Na^{+ j}, Cl^{− j} mannitol^l	Via both blood–brain barrier and perivascular routes	c. 1–2
Efflux via perivascular routes only
Sucrose, inulin, albumin, larger dextrans and PEGs^m	Used as markers for perivascular efflux	c. 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
^aSee Sect. 5.1
^bSee Sect. 5.2
^cClearance known to be large but difficult to measure
^dSee Fig. 8
^eSee Sect. 5.3 and Appendix D
^fSee Sect. 5.4
^gSee Table 1
^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
ⁱSee Appendix E, NKCC1 is the Na⁺, K⁺, 2Cl⁻—cotransporter; ^jsee Appendix E
^kSee Sect. 5.7.3
^lSee Appendix B
^mNegligible blood–brain barrier clearance, see Sect. 3 and Appendix B

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