Skip to main content

Hypothermia-induced reduction in the permeation of radiolabelled tracer substances across the blood-brain barrier

Acta Neuropathologica volume 60, pages 61–69 (1983)Cite this article

Summary

The permeability of the rat blood-brain barrier during different levels of hypothermia was examined using a new and more sensitive quantitative radiotracer technique. In contrast to the findings of previous studies, tracer permeation as measured here by the calculated cerebrovascular permeability-area product (PA), did not increase during hypothermia. Rather, rats maintained at specific temperatures between 30–16° C (1h) by contact surface cooling, displayed lowered permeation (PA) of i.v. injected14C-sucrose,125I-bovine serum albumin and3H-α-amino-isobutyric acid in all brain regions examined. This effect was temperature-dependent and reversible on rewarming to normothermic temperature. Elevated plasma tracer concentration vs. time was characteristic of hypothermic rats except those cooled to 30° C. That no elevation in plasma tracer accompanied alterations in tracer permeation at 30° C, indicates hypothermic induced reductions in PA are independent of altered plasma tracer levels. Furthermore, the nature of α-amino-isobutyric acid to rapidly distribute to intracellular vs. extracellular sites suggests the effects of hypothermia seen here are due primarily to the condition of cerebrovascular membranes.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  • Balcalzo LV, Wolfson SK (1971) Preferential cerebral hypothermia. Arch Surg 103:393–397

    Google Scholar 

  • Baldwin M, Falindo A, Farrier R (1962) Cerebral reaction to Na fluorescein during profound hypothermia. Neurology 12:193–201

    Google Scholar 

  • Baldwin M, Farrier R, MacDonald F, Ommaya AK (1963) Cerebral deposition of drugs at low temperature. J Neurol Surg 20:637–646

    Google Scholar 

  • Blasberg RG (1977) Pharmacodynamics and the blood-brain barrier. Natl Cancer Inst Monogr 46:19–27

    Google Scholar 

  • Blasberg RG, Gazendam J, Patlack CS, Shapiro WS, Fenstermacher JD (1981) Changes in blood-brain transfer parameters induced by hyperosmolar intracarotid infusion and by metastatic tumor growth. In: Eisenberg HM, Suddith RL (eds) The cerebral microvasculature. Advances in experimental medicine and biology, vol 131, Plenum Press, New York, pp 307–319

    Google Scholar 

  • Bradbury MWB (1979) The concept of a blood-brain barrier. Wiley, Chichester

    Google Scholar 

  • Brendel W, Müller Ch, Reulen HJ, Messmer K (1966) Elektrolytveränderungen in tiefer Hypothermie. Pflügers Arch 288:220–239

    Google Scholar 

  • Brightman MW (1968) The intracerebral movement of proteins injected into blood and cerebrospinal fluid of mice. In Lajtha A, Ford DH (eds) Progress in brain research, vol 29. Elsevier, Amsterdam London New York, pp 19–40

    Google Scholar 

  • Chapman D, Cornell BA, Quinn PJ (1977) Phase transitions, protein aggregation and a new method for modulating membrane fluidity. In: Semenza G, Carafoli E (eds) Proceedings in life sciences. Biochemistry of membrane transport. Springer, Berlin Heidelberg New York, pp 72–85

    Google Scholar 

  • Collewijn H, Schadé JP (1962) Cerebral impedance changes in hypothermia. Arch Intern Physiol Biochem 70:200–210

    Google Scholar 

  • Collewijn H, Schadé JP (1964) Conductivity of the cerebral cortex after circulatory arrest from 37° C to 18° C. Arch Intern Physiol Biochem 72:181–193

    Google Scholar 

  • Connolly JE, Boyd RJ, Calvin JW (1962) The protective effect of hypothermia in cerebral ischemia: Experimental and clinical applications by selective brain cocling in the human. Surgery 52:15–24

    Google Scholar 

  • Davson H (1965) The extracellular space of the brain. In: De Robertis EDP, Carrea R (eds) Biology of neuroglia. Progress in brain research, vol. 12. Elsevier, Amsterdam London New York, pp 124–234

    Google Scholar 

  • Davson H (1976) The blood-brain barrier. J Physiol (Lond) 225:1–28

    Google Scholar 

  • Davson H, Spaziani E (1962) Effect of hypothermia on certain aspects of the cerebrospinal fluid. Exp Neurol 6:118–128

    Google Scholar 

  • Deterling RA, Nelson E, Bhonslau, S, Howland L (1955) Study of basic physiologic changes associated with hypothermia. Arch Surg 70:87–94

    Google Scholar 

  • Farrand RL, Horvath SM (1959) Body fluid shifts in the dog during hypothermia. Am J Physiol 197:499–501

    Google Scholar 

  • Ferguson RK, Woodbury DM (1969) Penetration of14C-inulin and14C-sucrose into brain, cerebrospinal fluid, and skeletal muscle of developing rats. Exp Brain Res 7:181–194

    Google Scholar 

  • Fenstermacher JD, Blasberg RG, Patlak CS (1981) Methods for quantifying the transport of drugs across brain barrier systems. Pharmacol Therap 14:217–248

    Google Scholar 

  • Fleming R (1954) Acid-base balance of the blood in dogs at reduced temperature. Arch Surg 68:145–152

    Google Scholar 

  • Haneda K, Sands MP, Thomas R, Merrick SH, Hessel II, EA, Dillard DH (1982) Circulatory dynamics during surface-induced hypothermia under halothane-ether azeotrope anaesthesia. Ann Thorac Surg 33:258–266

    Google Scholar 

  • Harris JH, Robertson JT, (1974) Ultrastructural alterations in the dog brain after profound hypothermia induced by extracorporeal circuit. Stroke 5:487–508

    Google Scholar 

  • Hearse DJ, Brainbridge MV, Jynge P (ed) (1981) Protection of the ischemic myocardium: Cardioplegia. Raven Press, New York

    Google Scholar 

  • Hervonen H, Steinwall O, Spatz M, Klatzo I (1981) Behaviour of the blood-brain barrier toward biogenic amines in experimental ischemia. In: Eisenberg HM, Suddith RL (eds) The cerebral microvasculature. Advances in experimental medical biology, vol 131. Plenum Press, New York, 295–306

    Google Scholar 

  • Jeppsson PG (1962) Studies on the blood-brain barrier in hypothermia. Acta Neurol Scand [Suppl 160] 38:1–229

    Google Scholar 

  • Johnstone M, Evans V, Murphy PV (1961) The halothane-ether azeotrope: an illogical mixture. Can Anaesthesiol Soc J 8:53–63

    Google Scholar 

  • Klatzo I, Choh Luh LI, Long DM, Bak AF, Mossakowski MJ, Parker LO, Rasmussen LE (1968) The effect of hypothermia on electric impedance and penetration of substances from the CSF into the periventricular brain tissue. In: Lajtha A, Ford DH (eds) Brain barrier systems. Progress in brain research, vol 29. Elsevier, Amsterdam London New York, pp 385–400

    Google Scholar 

  • Klatzo I, Miguel J, Ferris PJ, Prokop JO, Smith DE (1964) Observations on the passage of fluorescein labeled serum proteins from the cerebrospinal fluid. J Neuropathol Exp Neurol 23:18–35

    Google Scholar 

  • Kuttner R, Sims JA, Sordon MW (1961) The uptake of a metabolically inert amino acid by brain and other organs. J Neurochem 6:311–317

    Google Scholar 

  • Leaf A (1973) Cell swelling. A factor in ischemic tissue injury. Circulation 48:455–458

    Google Scholar 

  • Lewis, FJ, Ring DM, Alden JF (1956) A technique for total body cooling of the febrile, gravely ill patient. Surgery 40:465–470

    Google Scholar 

  • Li CL (1955) Action and resting potentials of cortical neurones. J Physiol 130:96–108

    Google Scholar 

  • Li CL (1958) Effect of cooling on neuromuscular transmission in the rat. Am J Physiol 194:200–206

    Google Scholar 

  • Li CL (1959) Cortical intracellular potentials and their response to strychnine. J Neurophysiol 22:436–450

    Google Scholar 

  • Li CL, Gouras P (1958) Effect of cooling on neuromuscular transmission in the frog. Am J Physiol 192:464–470

    Google Scholar 

  • Li CL, McIIwain H (1957) Maintenance of resting membrane potentials in slices of mammalian cerebral cortex and other tissues in vitro. J Physiol 139:178–190

    Google Scholar 

  • Lougheed WM, Sweet WH, White JC, Brewster WR (1955) Use of hypothermia in surgical treatment of cerebral vascular lesions; preliminary report. J Neurosurg 12:240–255

    Google Scholar 

  • Lourie H, Weinstein WJ, O'Leary JC (1960) Effect of hypothermia upon vital staining of the brain. J Nerv Ment Dis 130:1–5

    Google Scholar 

  • MacKnight AC, Leaf A (1977) Regulation of cellular volume. Physiol Rev 57:510–573

    Google Scholar 

  • McMurchie EJ, Raison JK, Cairncross KD (1973) Temperature-induced phase changes in membranes of heart: A contrast between the thermal response of poikilotherms and homeotherms. Comp Biochem Physiol 44B:1017–1026

    Google Scholar 

  • Negrin, J, Jr (1961) Selective local hypothermia in neurosurgery. NY J Med 61:2951–2965

    Google Scholar 

  • Ohno K, Pettigrew KD, Rapoport SI (1978) Lower limits of cerebrovascular permeability to nonelectrolytes in the conscious rat. Am J Physiol 235:299–307

    Google Scholar 

  • Pardridge WM, Oldendorf WH (1977) Transport of metabolic substrate through the blood-brain barrier. J Neurochemist 28:5–12

    Google Scholar 

  • Popovic V, Popovic P (1974) Hypothermia in biology and in medicine. Grune and Stratton, New York

    Google Scholar 

  • Preston E (1982) Failure of hyperthermia to open rat blood-brain barrier. Acta Neuropathol (Berl) 57:255–262

    Google Scholar 

  • Preston E, Haas N (1982) Test of a 2-compartment model for the assessment of blood-brain barrier permeability. Proc Can Fed Biol Soc 25:101P

    Google Scholar 

  • Prusiner S, Wolfson SK (1968) Hypothermic protection against cerebral edema of ischemia. Arch Neurol 19:623–627

    Google Scholar 

  • Rapoport SI (1976) Blood-brain barrier in physiology and medicine Raven Press, New York

    Google Scholar 

  • Rapoport SI, Ohno K, Fredericks WR, Pettigrew KD (1973) Regional cerebrovascular permeability to14C-sucrose after osmotic opening of the blood-brain barrier. Brain Res 150:653–657

    Google Scholar 

  • Reed DJ, Woodbury DM (1963) Kinetics of movement of iodide, inulin, sucrose, and radio-iodinated serum albumin in the central nervous system and cerebrospinal fluid of the rat. J Physiol 169:816–850

    Google Scholar 

  • Reulen HJ, Aigner P, Brendel W, Messner K (1966) Elektrolytveränderungen in tiefer Hypothermie. I. Die Wirkung akuter Auskühlung bis 0°C und Wiedererwärmung. Pflügers Arch 228:197–219

    Google Scholar 

  • Rodbard S, Saiki H, Malin A, Young C (1951) Significance of changes in plasma and extracellular volumes in induced hyperthermia and hypothermia. Am J Physiol 167:485–498

    Google Scholar 

  • Rosomoff HL (1959) Protective effects of hypothermia against pathological processes of the nervous system. Ann NY Acad Sci 80:475–486

    Google Scholar 

  • Rosomoff HL, Gilbert R (1955) Brain volume and cerebrospinal fluid pressure during hypothermia. Am J Physiol 183:19–22

    Google Scholar 

  • Rosomoff HL, Holaday DA (1954) Cerebral blood flow and cerebral oxygen consumption during hypothermia. Am J Physiol 179:85–88

    Google Scholar 

  • Scholfield PG, Clayman S (1968) Mechanisms of metabolite transport in various tissues. In: Lajtha A, Ford DM (eds) Brain barrier systems. Progress in brain research, vol 29. Elsevier, Amsterdam London New York, pp 173–184

    Google Scholar 

  • Segadal L, Svanes K, Romslo I (1979) Blood flow distribution and microcirculation under profound hypothermia and extreme hemodilution. Microvasc Res 17:207

    Google Scholar 

  • Swan H (1974) Thermoregulation and bioenergetics. American Elsevier, New York

    Google Scholar 

  • Tabaddor K, Caroner TJ, Walker AE (1972) Cerebral circulation and metabolism at hypothermia. Neurology 22:1065–1070

    Google Scholar 

  • Togashi T (1962) Experimental studies on hypothermia from the neurosurgical point of view. Sapporo Med J 21:273–296

    Google Scholar 

  • Van Gelder NM, Elliott KAC (1958) Disposition of α-aminobutyric acid administered to mammals. J Neurochem 3:139–143

    Google Scholar 

  • Venugopal P, Olszowka J, Wagner H, Lambert E, Subramanian S (1973) Early correction of congenital heart disease with surface-induced deep hypothermia and circulatory arrest. J Thorac Cardiovasc Surg 66:375–386

    Google Scholar 

  • Volkert WA, Tempel GE, Musacchia XJ (1976) Renal function in hypothermic hamsters. In: Jansky, L, Musachia XJ (eds) Regulation of depressed metabolism and thermogenesis. Thomas, Springfield, Ill pp 158–173

    Google Scholar 

  • Wells LA (1972) Permeability of the blood-brain barrier system to rubidium in enthermia hibernation and hypothermia. Comp Biochem Physiol 42A:551–557

    Google Scholar 

  • Wells LA (1973) Alteration of the blood brain barrier system by hypothermia critical time period vs critical To. Comp Biochem Physiol A 44:293–296

    Google Scholar 

  • Woodhall B, Sealy WC, Hall KD, Floyd WL (1960) Craniotomy under conditions of guinidine-protected carcioplegia and profound hypothermia. Ann Surg 152:37–44

    Google Scholar 

  • Wyler F (1974) Effect of general anaesthesia on distribution of cardiac output and organ blood flow in the rabbit: halothane and chloraloseurethane. J Surg Res 17:381–386

    Google Scholar 

  • Zarins CK, Skinner DB (1973) Circulation in profound hypothermia. J Surg Res 14:97–104

    Google Scholar 

Download references

Author information

Affiliations

  1. Division of Biological Sciences, National Research Council of Canada, K1A 0R6, Ottawa, Canada

    A. Krantis

Authors
  1. A. Krantis
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

N.R.C.C. No. 21110

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Krantis, A. Hypothermia-induced reduction in the permeation of radiolabelled tracer substances across the blood-brain barrier. Acta Neuropathol 60, 61–69 (1983). https://doi.org/10.1007/BF00685348

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00685348

Key words

  • Blood-brain barrier
  • Hypothermia
  • Radiotracer
  • Rats