Summary
The blood-brain barrier was opened by intracarotid infusion of 5 mg protamine sulfate in 100 μl 0.9% NaCl over a period of 30 s either alone or followed by infusion of 10 mg L-glutamate in 0.9% NaCl. Glutamate alone was infused in four control rats. Cisternal cerebrospinal fluid (CSF) was withdrawn before protamine administration and before the brains were fixed in situ 1, 24 or 72 h later. The albumin extravasation and glial reactivity was evaluated by immunohistochemistry on paraffin sections. The CSF albumin was significantly increased in both the protamine and protamine/glutamate groups but remained high at 24 and 72 h in the protamine/glutamate group only. Spongiotic lesions with shrunken nerve cells were observed 1 and 24 h after infusion of protamine alone or in combination with glutamate. Whereas such changes were not seen 72 h after protamine infusion, they remained and had progressed at 72 h in the protamine/glutamate group, indicating that glutamate induces delayed cellular damage when given access to the brain through an altered blood-brain barrier.
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Baethmann A, Oettinger W, Rothenfusser W, Kempski O, Unterberg A, Geiger R (1980) Brain edema factors. Current state with particular reference to plasma constituents and glutamate. Adv Neurol 28:171–195
Baethmann A, Maier-Hauff K, Schürer L, Lange M, GuggenbichlerC, Vogt W, Jacob K, Kempski O (1989) Release of glutamate and of free fatty acids in vasogenic brain edema. J Neurosurg 70:578–591
Choi DW (1988) Glutamate neurotoxicity and diseases of the nervous system. Neuron 1:623–634
Choi DW (1990) Methods for antagonizing glutamate neurotoxicity. Cerebrovasc Brain Metab Rev 2:105–147
Fredriksson K, Kalimo H, Nordborg C, Johansson BB, Olsson Y (1988) Nerve cell injury in the brain of stroke-prone spontaneously hypertensive rats. Acta Neuropathol 76:227–237
Hardebo JE, Kåhrström J (1985) Endothelial negative surface charges areas and blood-brain barrier function. Acta Physiol Scand 125:495–499
Johansson BB, Nordborg C, Westergren I (1990) Neuronal injury after a transient opening of the blood-brain barrier: modifying factors. In: Johansson BB, Owman C, Widner H (eds) Pathophysiology of the blood-brain barrier. Elsevier, Amsterdam, pp 145–157
Kempski O, van Andrian U, Schürer L, Baethmann A (1990) Intravenous glutamate enhances edema formation after a freezing lesion. Adv Neurol 52:219–222
Laurell C-B (1966) Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies, Anal Biochem 15:45–52
McBean GJ, Roberts PJ (1984) Chronic infusion of l-glutamate causes neurotoxicity in rat striatum. Brain Res 290:372–375
Mangano RM, Schwarcz R (1983) Chronic infusion of endogenous excitatory amino acids into rat striatum and hippocampus. Brain Res Bull 10:47–51
Nagy Z, Peters H, Huttner I (1983) Charge-related alterations of the cerebral endothelium. Lab Invest 49:662–671
Olney JW, Sharpe LG, Feigin RD (1972) Glutamate-induced brain damage in infant primates. J Neuropathol Exp Neurol 31:464–488
Ranson RW, Stec NL (1988) Cooperative modulation of [3H] MK-801 binding to the N-methyl-d-aspartate receptorion channel complex by l-glutamate, glycine, and polyamines. Neurochem 51:830–836
Rothman SM, Olney JW (1986) Glutamate and the pathophysiology of hypoxic-ischemic brain damage. Ann Neurol 19:105–111
Salahuddin TS, Johansson BB, Kalimo H, Olsson Y (1988) Structural changes in the rat brain after carotid infusions of hyperosmolar solutions: a light microscopic and immunohistochemical study. Neuropathol Appl Neurobiol 14:467–482
Salahuddin TS, Johansson BB, Kalimo H, Olsson Y (1988) Structural changes in the rat brain after carotid infusions of hyperosmolar solutions. An electron microscopic study. Acta Neuropathol 77:5–13
Sokrab TEO, Johansson BB, Kalimo H, Olsson Y (1988) A transient opening of the blood-brain barrier can lead to brain damage. Extravasation of serum proteins and cellular changes in rats subjected to aortic compression. Acta Neuropathol (Berl) 75:557–565
Sokrab TEO, Kalimo H, Johansson BB (1990) Parenchymal changes related to plasma protein extravasation in experimental seizures. Epilepsia 31:1–8
Van Harreveld A, Fifkova E (1971) Light and electron microscopic changes in central nervous tissue after electrophoretic injection of glutamate. Exp Mol Pathol 15:61–81
Westergren I, Johansson BB (1990) Albumin content in brain and CSF after intracarotid infusion of protamine sulphate. A longitudinal study. Exp Neurol 107:192–196
Westergren I, Johansson BB (1991) Changes in physiological parameters of rat cerebrospinal fluid during chronic sampling. Evaluation of two sampling techniques. Brain Res Bull 27:283–286
Westergren I, Johansson BB (1992) NBQX, an AMPA-anta-gonist, reduces glutamate-mediated brain edema. Brain Res 573:324–326
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Supported by grants from the Swedish Medical Research Council (project 14x-4968), from King Gustaf V and Queen Victoria's Foundation, from the Medical Faculty, Lund University, and from 1987 Foundation for Stroke Research.
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Westergren, I., Nordborg, C. & Johansson, B.B. Glutamate enhances brain damage and albumin content in cerebrospinal fluid after intracarotid protamine infusion. Acta Neuropathol 85, 285–290 (1993). https://doi.org/10.1007/BF00227724
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DOI: https://doi.org/10.1007/BF00227724