A simple saline perfusion system was used to investigate the effects of hyperosmolar solutions of arabinose and mannitol upon the permeability of the blood-brain barrier. The small, polar molecule [14C]mannitol and the larger, visual marker Evans blue were used as indicators of barrier integrity in the perfused energydepleted brain. One-minute perfusion of hyperosmolar solutions consistently opened the barrier suggesting that the mechanism of osmotic barrier opening is independent of energy-producing metabolism. The accumulation of radiolabel in the brain was expressed as the ratio of tissue to perfusate radioactivity (Rt/Rp) and, for cerebrum, this increased from a control value of 0.0022 ± 0.0007 (mean ± SEM; n = 4) to a value of 0.0124 ± 0.0008 (n = 4) following 0.9 M arabinose and to 0.0495 ± 0.0072 (n = 4) following 1.8 M arabinose. There was a significant reduction of water content of hyperosmolar perfused brains. These findings support the hypothesis that osmotic barrier opening is the result of the passive shrinkage of endothelial cells and the surrounding tissue.
BrightmanMWHoriMRapoportSIReeseTSWestergaardE, (1973) Osmotic opening of tight junctions in cerebral endothelium, J Comp Neurol152;317–26
2.
BromanT, (1950) Supravital analysis of disorders in cerebrovascular permeability. III. A critical analysis of the technique and results obtained in experimental animals, Acta Psychiatrics25:19–31
3.
BromanTGrontoftOSteinwallO, (1965) Comparative intravital and postmortem studies on chemically induced blood-brain barrier damage tested with trypan blue. Acta Neurol Scand41:527–38
4.
Cervós-NavarroJArtigasJMrsuljaBJ, (1983) Morphofunctional aspects of the normal and pathological blood-brain barrier. Acta Neuropathol (suppl VIII):1–19
5.
Dorovini-ZisKBowmanPDBetzALGoldsteinGW, (1984) Hyperosmotic arabinose solutions open the tight junctions between brain capillary endothelial cells in tissue culture. Brain Res302:383–86
6.
EidelbergEFishmanJHamsML, (1967) Penetration of sugars across the blood-brain barrier. J Physiol191:47–57
7.
FieschiCLenziGLZanetteEOrziFPasseroS, (1980) Effects on EEG of the osmotic opening of the blood-brain barrier in rats, Life Sci27:239–43
8.
GreenwoodJLuthertPJPrattOELantosPL, (1985) Maintenance of the integrity of the blood-brain barrier in the rat during an in situ saline-based perfusion. Neurosci Lett56:223–27
9.
GreenwoodJLantosPLLuthertPJPrattOE, (1986a) The transport of D-glucose across the blood-brain barrier of the rat in the presence of the metabolic inhibitor 2,4-dinitrophenol. J Physiol372:70P
10.
GreenwoodJLantosPLLuthertPJPrattOE, (1986b) Hyperosmolar opening of the rat blood-brain barrier in the absence of energy-producing metabolism. J Physiol374:19P
11.
GulatiAAgarwalSKShuklaRSrimalRCDhawanBN, (1985) The mechanism of opening of the blood-brain barrier by hypertonic saline, Neuropharmacol24:909–13
12.
HanssonHAJohanssonBB, (1980) Induction of pinocytosis in cerebral vessels by acute hypertension and by hyperosmolar solutions. J Neurosci Res5:183–190
13.
HardeboJE, (1980) A time study in rat on the opening and reclosure of the blood-brain barrier after hypertensive or hypertonic insult. Exp Neurol70:155–66
14.
HardeboJENilssonB, (1980) Hemodynamic changes in brain caused by local infusion of hyperosmolar solutions, in particular relation to blood-brain barrier opening. Brain Res181:49–59
15.
HiesigerEMVoorhiesRMBaslerGALipschutzLEPosnerJBShapiroWR, (1986) Opening the blood-brain and blood-tumor barriers in experimental rat brain tumors: The effect of intracarotid hyperosmolar mannitol on capillary permeability and blood flow. Ann Neurol19:50–9
16.
HossmanK-AOlssonY, (1971) Influence of ischemia on the passage of protein tracers across capillaries in certain blood-brain barrier injuries. Acta Neuropathol (Berl)18:113–22
17.
HouthoffHJGoKGGerritsPO, (1982) The mechanism of blood-brain barrier impairment by hyperosmolar perfusion. Acta Neuropathol (Berl)56:99–112
18.
KuroiwaTTingPMartinezHKlatzoI, (1985) The biphasic opening of the blood-brain barrier to proteins following temporary middle cerebral artery occlusionActa Neuropathol (Berl)68:122–9
19.
LeeJCOlszewskiJ, (1961) Increased cerebrovascular permeability after repeated electroshocks. Neurology11:515–9
20.
LehtosaloJPanulaPLaitinenLA, (1982) The permeability alteration of brain and spinal cord vasculature to horseradish peroxidase during experimental decompression sickness as compared to the alteration in permeability induced by hyperosmolar solution. Acta Neuropathol (Berl)57:179–87
21.
LevinVAWrightDCLandahlHDPatlakCSCsejteyJ, (1980) In situ drug delivery. Br J Cancer (suppl IV) 41:74–8
22.
LorenzoAVBarlowCF, (1967) Effect of strychnine upon entry of 35S-sulphate into the central nervous system. J Pharmacol157:555–64
23.
LuthertPJGreenwoodJPrattOELantosPL, (1987) The effect of a metabolic inhibitor upon the properties of the cerebral vasculature during a whole-head saline perfusion of the rat. Q J Exp Physiol72:129–41
24.
MayhanWGHeistadDD, (1985) Permeability of blood-brain barrier to various sized molecules. Am J Physiol248:H712–8
25.
NagyZPappiusHMMathiesonGHuttnerI, (1979) Opening of tight junctions in cerebral endothelium. I. Effect of hyperosmolar mannitol infused through the internal carotid artery. J Comp Neurol185:569–78
26.
NakagawaHGroothuisDBlasbergRG, (1984) The effect of graded hypertonic intracarotid infusions in drug delivery to experimental RG-2 gliomas. Neurol32:1571–81
27.
NeuweltEABarnettPAGlasbergM, (1983) Successful treatment of primary nervous system lymphomas with chemotherapy after osmotic blood-brain barrier opening. Neurosurg12:662–71
28.
NeuweltEARapoportSI, (1984) Modification of the blood-brain barrier in the chemotherapy of malignant brain tumours. Fed Proc43:214–9
29.
NeuweltEABarrangerJAPagelMAQuirkJMBradyROFrenkelEP, (1984) Delivery of active hexosaminidase across the blood-brain barrier in rats. Neurology34:1012–9
30.
PappiusHMSavakiHEFieschiCRapoportSISokoloffL, (1979) Osmotic opening of the blood-brain barrier and local cerebral glucose utilization. Ann Neurol5:211–9
31.
PickardJDDurityFWelshFALangfittTAHarperAMMacKenzieET, (1977) Osmotic opening of the blood-brain barrier: Value in pharamacological studies on the cerebral circulation. Brain Res122:170–6
32.
RapoportSI, (1970) Effect of concentrated solutions on blood-brain barrier. Am J Physiol219:270–4
33.
RapoportSIFredericksWROhnoKPettigrewKD, (1980) Quantitative aspects of reversible osmotic opening of the blood-brain barrier. Am J Physiol238:R421–31
34.
RapoportSIHoriMKlatzoI, (1972) Testing of a hypothesis for osmotic opening of the blood-brain barrier. Am J Physiol223:323–31
35.
RapoportSIMatthewsKThompsonHKPettigrewKD, (1977) Osmotic opening of the blood-brain barrier in the rhesus monkey without measurable brain edema. Brain Res136:23–9
36.
RapoportSIRobinsonPJ, (1986) Tight-junctional modification as the basis of osmotic opening of the blood-brain barrier. Ann NY Acad Sci481:250–66
37.
ReeseTSKarnovskyMJ, (1967) Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol34:207–17
38.
ThompsonAM, (1970) Hyperosmotic effects on brain uptake of non-electrolytes. In: Capillary permeability (CroneCLassenNA, eds), Copenhagen, Munksgaard, pp 459–67
39.
WestergaardEGoGKlatzoISpatzM, (1976) Increased permeability of cerebral vessels to horseradish peroxidase induced by ischemia in Mongolian gerbils. Acta Neuropathol (Berl)35:307–25
40.
WestergaardEVan DeursBBrondstedHE, (1977) Increased vesicular transfer of horseradish peroxidase across cerebral endothelium, evoked by acute hypertension. Acta Neuropathol (Berl)37:141–152
