Stroke induces histamine accumulation and mast cell degranulation in the neonatal rat brain.
Inflammatory processes are a major cause of hypoxic-ischemic brain damage. The present study focuses on both the cerebral histamine system and mast cells in a model of transient focal ischemia induced by permanent left middle cerebral artery, and homolateral transient common carotid artery occlusion (50 minutes) in the P7 newborn rat. Immunohistochemical analysis revealed that ischemia induces histamine (HA) accumulation in the core of the infarct 6-12 h post-ischemia, and in the penumbra at 24-48 h, although in situ hybridization failed to detect any histidine decarboxylase gene transcripts in these regions. Immunohistochemical co-localization of HA with the MAP2 marker revealed that HA accumulates in neuronal cells before they degenerate, and is accompanied by a very significant increase in the number of mast cells at 12 h and 48 h of reperfusion. In mast cells, histamine immunoreactivity is detected at 2, 6 and 12 h after ischemia, whereas it disappears at 24 h, when a concomitant degranulation of mast cells is observed. Taken together, these data suggest that the recruitment of cerebral mast cells releasing histamine may contribute to ischemia-induced neuronal death in the immature brain.
Biran
V
V
UMR702 Université Pierre et Marie Curie-Paris, and Service de Néonatologie, Hôpital Armand Trousseau, Paris, France.
Cochois
V
V
Karroubi
A
A
Arrang
J M
JM
Charriaut-Marlangue
C
C
Héron
A
A
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D016923:Cell Death; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D006632:Histamine / Q000378:metabolism*; D006636:Histamine Release; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D008407:Mast Cells / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D020521:Stroke / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
D015415:Biomarkers; D008869:Microtubule-Associated Proteins; D006632:Histamine