ELSEVIER Neuroscience Letters 195 (1995) 25-28 NEUROSCIEHC[ IEITERS The role of cerebral microvessels in the elimination of histamine released during postasphyxial reperfusion in newborn piglets J6zsef Kov~icsa, J6zsef Kaszaki b, P6ter Temesv~iria, Andr~is Czesznak c, Csongor S. Abrah~n~, Ferenc Jo6 c,* aDepartment of Pediatrics, Albert Szent-Gy6rgyi Medical University, P.O. Box 471, H-6701, Szeged, Hungary blnstitate of Experimental Surgery, Albert Szent-GyOrgyi Medical University, P.O. Box 471, H-6701, Szeged, Hungary C Laboratory of Molecular Neurobiology, Institute of Biophysics, Biological Research Center, P.O. Box 521, 11-6701, Szeged, Hungary Received 9 June 1995; accepted 21 June 1995 Abstract Histamine, released from intracerebral sources during hypoxic-ischemic conditions, may take part in the pathogenesis of neonatal brain injuries. In order to elucidate the possible role of cerebral microvessels in the elimination of histamine from the extracellular space, we determined the concentration of histamine using a modified radioenzymatic method in plasma taken from the internal jugular vein, in cerebrospinal fluid, and in capillary-rich fraction of cerebral microvessels prepared from cortex in 12 sham-operated piglets. Then, bilateral pneumothorax was induced in 20 piglets, samples were taken from the same compartments as from the controls before and during asphyxia, as well as 15 and 180 min thereafter, respectively. Plasma histamine level was significantly (P < 0.05) elevated in animals during hypoxic cardiovascular and metabolic failure (13.5 _+ 1.9 nM 1-1) compared to the value measured in the control group (2.2 ± 0.5 nM l-l), preceding any detectable change of histamine concentration in cerebrospinal fluid (5.2 _+ t.9 versus 3.8 ± 1.1 nM l- l, respectively) or in cerebral microvessels (8.4 ± 0.8 versus 7.1 ± 0.6 pM (mg protein)-1). After resuscitation, histamine levels in plasma samples remained high during the early (15 min, 16.2 ± 4.3 nM x 1 -l) and late (180 min, 15.3 + 2.9 nM 1-1) reperfusion period. By contrast, histamine concentration was increased considerably (P<0.05) in cerebrospinal fluid samples obtained 15 min (12.8 _+6.5 nM 1-1), but not 180 min (5.2 ± 1.9 nM 1-1) after resuscitation. Significant (P < 0.05) elevation of histamine concentration was seen only in cerebral microvessels prepared from asphyxiated piglets 180 min after resuscitation (18.6 _+5.3 versus 7.2 _+ 1.6 pM (mg protein)-l). We conclude that cerebral microvessels may take part in the elimination of histamine from the extracellular space during recovery of asphyxia in newborn pigs. Keywords: Histamine; Blood-brain barrier; Neonatal hypoxia-ischemia The presence of histamine in the central nervous sys- tem has long been revealed and its role in the neurohu- moral transmission has been shown [17]. Intracerebral histamine is also a known regulator of cerebral blood flow [9]; it is released under pathological conditions [1,14,15] and plays an important role in brain edema for- mation [9,12]. There are at least three distinct cerebral histamine pools within the brain, such as neuronal ele- ments, perivascular mast cells and cerebral endothelium. Brain capillaries have low activity of the histamine syn- thesizing (L-histidine decarboxylase) and metabolizing * Corresponding author, Tel.: +36 62 432232; Fax: +36 62 433133; E-mail: frici@everx.szbk.u-szeged.hu. (histamine-N-methyltransferase) enzymes [13], histamine receptors (mainly H2-type), however, were supposed to be present on both sides of the blood-brain barrier (BBB) [12]. Indeed, our recent direct in vitro study revealed that cultured primary cerebral endothelial cells have the abil- ity to take up histamine from both luminal and abluminal sides but they released it mainly luminally [10]. This finding suggested that the brain microvessels may use the endothelial polarized transport-system in pathological conditions, providing an important protective mechanism against the increase of cerebral histamine concentration. The aim of the present study was to check the changes of histamine concentrations simultaneously in different compartments (plasma from the internal jugular vein; 0304-3940/95/$09.50 © 1995 Elsevier Science Ireland Ltd. All rights reserved SSDI 0304-3940(95)11770-T