Summary
Using lanthanum nitrate as a tracer, the permeability of rat cortical blood vessels was investigated during regional hypothermia of the cerebral cortex by electron microscopy. The concentration of K+ ions in the extracellular space of the cortex was determined using an ion-selective micro-electrode. Only at temperatures below about 7°C was an extravasation of tracer observed in a number of cortical capillaries and arterioles, where some of the tight junctions became widened and permeable. In a few cases penetration of the tracer into vacuoles of phagocytosing pericytes or macrophages was found. The extravasation of the tracer could mainly be observed in vessels on and below the cortical surface, less often in deeper cortical parts. At the same degree of hypothermia, the K+ concentration in the extracellular space increased, reaching a maximal value of ca. 6 mmol/l at a depth of about 200 μm. As could be shown in one previous experiment, the K+ concentration reached normal values again after rewarming to 37°C for 15 min, but an extravasation of the tracer was still observed. The role of the endothelial tight junctions and of the astrocytes together with the pericytes (or macrophages) is discussed regarding their importance for the effectiveness of the blood-brain barrier system.
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References
Bakay L, ul Haque I (1964) Morphological and chemical studies in cerebral edema. I. Cold induced edema. J Neuropathol Exp Neurol 23:393–418
Baldwin M (1968) Cerebral argyria after hibernation. Neurology 18:813–816
Baldwin M, Galindo A, Farrier R (1962) Cerebral reaction to sodium fluorescein during profound hypothermia. Neurology 12:193–201
Baldwin M, Farrier R, MacDonald F, Ommaya AK (1963) Cerebral deposition of drugs at low temperatures. J Neurosurg 20:637–646
Beggs JL, Waggener JD (1976) Transendothelial vesicular transport of protein following compression injury to the spinal cord. Biochem Pharmacol 35:2273–2282
Betz AL (1985) Epithelial properties of brain capillary endothelium. Fed Proc 44:2614–2615
Bradbury M (1980) The concept of a blood-brain barrier. Wiley and Sons, Chichester
Bradbury MWB (1985) The blood-brain barrier: transport across the cerebral endothelium. Circ Res 57:213–222
Brendel W, Müller C, Reulen HJ, Messmer K (1966) Elektrolytveränderungen in tiefer Hypothermie. I. Beziehungen zur klinischen und biologischen Überlebenszeit. Pflügers Arch 288:220–239
Brightman MW, Reese TS, Vick NA, Bigner DD (1971) A mechanism underlying the lack of a blood-brain barrier to peroxidase in virally induced brain tumors. J Neuropathol Exp Neurol 30:139–140
Cancilla PA, Baker RN, Pollock PS, Frommes SP (1972) The reaction of pericytes of the central nervous system to exogenous protein. Lab Invest 26:376–383
Cancilla PA, Frommes SP, Kahn LE, De Bault LE (1979) Regeneration of cerebral microvessels. A morphologic and histochemical study after local freeze-injury. Lab Invest 40:74–82
Firth JA (1977) Cytochemical localization of the K+ regulation interface between blood and brain. Experientia 33:1093–1094
Harris JH, Robertson JT (1974) Ultrastructural alterations in the dog brain after profound hypothermia induced by extracoporeal circuit. Stroke 5:487–508
Jeppsson PG (1962) Studies on the blood-brain barrier in hypothermia. An experimental investigation in the rabbit with special reference to the effect of intracarotid injection of iodopyracet on the passage of trypan blue into the brain parenchyma. Acta Neurol Scand [Suppl] 1–229
Kimelberg HK (1986) Occurrence and functional significance of serotonin and catecholamine uptake by astrocytes. Biochem Pharmacol 35:2273–2282
Klatzo I, Piraux A, Laskowski EJ (1958) The relationship between edema, blood-brain-barrier and tissue elements in a local brain injury. J Neuropathol Exp Neurol 17:548–564
Krantis A (1983) Hypothermia-induced reduction in the permeation of radiolabeled tracer substances across the blood-brain barrier. Acta Neuropathol (Berl) 60:61–69
Krisch B, Leonhardt H, Oksche A (1984) Compartments and perivascular arrangements of the meninges covering the cerebral cortex of the rat. Cell Tissue Res 238:459–474
Laskowski EJ, Klatzo I, Baldwin M (1960) Experimental study of the effects of hypothermia on local brain injury. Neurology 10:499–505
Lee JC, Bakay L (1966) Ultrastructural changes in the edematous central nervous system. II. Cold-induced edema. Arch Neurol 14:36–49
Lehmenkühler A, Kersting U, Richter A, Boerrigter P (1986) Relations of bioelectric activity, extracellular ion concentrations and extracellular volume in cortical epileptic foci. In: Speckmann EJ, Schulze H, Walden J (eds) Epilepsy and calcium. Urban and Schwarzenberg, München Berlin Baltimore, pp 227–245
Long DM (1970) Capillary ultrastructure and the blood-brain barrier in human malignant brain tumors. J Neurosurg 32:127–144
Lossinsky AS, Vorbrodt AW, Wisniewski HM, Iwanowski L (1981) Ultracytochemical evidence for endothelial channellysosome connections in mouse brain following blood-brain barrier changes. Acta Neuropathol (Berl) 53:197–202
Lossinsky AS, Vorbrodt AW, Wisniewski HM (1983) Ultracytochemical studies of vesicular and canalicular transport structures in the injured mammalian blood-brain barrier. Acta Neuropathol (Berl) 61:239–245
Lourie H, Weinstein WJ, O'Leary JL (1960) Effect of hypothermia upon vital staining of the brain. A study of the blood-brain barrier. J Nerv Ment Dis 130:1–5
MacKenzie ET, Pickard JD, Hardebo JE (1977) Blood-brain barrier, amines and the cerebral circulation: problems and approaches. In: Owman C, Edvinsson L (eds) Neurogenic control of the brain circulation. Pergamon Press, Oxford, pp 231–243
Miller DR, Hallaba MAS, Steegman AT (1965) Effect of profound hypothermia with circulatory arrest in dogs. Special reference to changes in cerebrovascular permeability. Ann Surgery 161:272–285
Nagy Z, Mathieson G, Hüttner I (1979) Opening of tight junctions in cerebral endothelium. II. Effect of pressurepulse-induced acute arterial hypertension. J Comp Neurol 185:579–586
Newman EA (1986) High potassium conductance in astrocyte endfeet. Science 233:453–455
Petito CK, Schaefer JA, Plum, F (1977) Ultrastructural characteristics of the brain and blood-brain barrier in experimental seizures. Brain Res 127:251–267
Rapoport SI (1983) Passage of proteins from blood to cerebrospinal fluid. Model for transfer by pores and vesicles. In: Wood JH (ed) Neurobiology of cerebrospinal fluid, vol 2. Plenum, New York, pp 233–245
Simionescu N (1983) Cellular aspects of transcapillary exchange. Physiol Rev 63:1536–1579
Stewart PA, Hayakawa K, Kayakawa E, Farrell CL Del Maestro RF (1985) A quantitative study of blood-brain barrier permeability ultrastructure in a new rat glioma model. Acta Neuropathol (Berl) 67:96–102
Van Deurs B (1976) Observations on the blood-brain barrier in hypertensive rats, with particular reference to phagocytic pericytes. J Ultrastruct Res 56:65–77
Wells LA (1972a) Permeability of the blood-brain barrier system to rubidium in euthermia, hibernation and hypothermia. Comp Biochem Physiol 42A:551–557
Wells LA (1972b) The effects of low body temperatures on deposition of tracers in the mammalian brain. Cryobiology 9:367–382
Wells LA (1973) Alterations of the blood-brain barrier system by hypothermia: critical time period vs. critical temperature. Comp Biochem Physiol 44A:293–296
Wilmes FJ, Garcia JH, Conger KA, Chui-Wilmes E (1983) Mechanisms of blood-brain barrier breakdown after microembolization of the cat's brain. J Neuropathol Exp Neurol 42:421–438
Wisniewski HM, Lossinsky AS, Moretz RC, Vorbrodt AW, Lassmann H, Carp RI (1983) Increased blood-brain barrier permeability in scrapie-infected mice. J Neuropathol Exp Neurol 42:615–626
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Schindelmeiser, J., Bergmann, M., Lehmenkühler, A. et al. Tracer permeability of rat cortical blood vessels during regional hypothermia. Acta Neuropathol 73, 349–356 (1987). https://doi.org/10.1007/BF00688258
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DOI: https://doi.org/10.1007/BF00688258