Summary
The possibility that 5-HT is involved in the pathophysiology of the blood-brain barrier (BBB) and subsequent brain damage via a receptor mediated mechanism was examined in a rat model of heat stress. Exposure of young rats (age 8–9 weeks) to heat at 38° C in a biological oxygen demand (BOD) incubator for 4 h resulted in a marked increase in the permeability of the blood-brain barrier (BBB) to Evans blue, 131I-sodium and lanthanum in the cerebral cortex, cerebellum, hippocampus, thalamus, hypothalamus and brain stem. These brain regions exhibited 3–4% increase in brain water content and 30–40% reduction in the cerebral blood flow (CBF). Morphological examinations showed upregulation of heat shock protein (HSP) 72 kD immunostaining along with distorted neurones, glial cells, perivascular edema, and myelin disruption. Pretreatment with 5-HT2 receptor antagonists cyproheptadine and ketanserin markedly reduced the BBB breakdown and brain edema formation. The CBF restored to normal values. Occurrence of HSP response and cell reactions were much less evident. This suggests that 5-HT participates in the pathophysiology of BBB breakdown and resulting brain damage in heat stress via 5-HT2 receptors.
Résumé
L’implication possible de la 5-HT, médiée par un récepteur spécifique, dans la pathophysiologie de la BHE conduisant à des lésions cérébrales a été étudiée dans le modèle animal de stress à la chaleur chez le rat. L’exposition de jeunes rats (8–9 semaines) à une température de 38° C pendant 4 heures dans un incubateur régulant le taux d’oxygène physiologique conduit à un accroissement de la perméablité de la BHE pour le bleu Evans, l’iode 125 et le lanthane dans le cortex cérébral, l’hippocampe, le thalamus, l’hypothalamus et le bulbe cervical.Ces différentes régions présentent une augmentation de 3 a 4% de la teneur en eau du parenchyme cérébral et une diminution de 30 a 40% du flux sanguin cérébral. Des examens histologiques montrent une surexpression de la protéine heat shock (HSP) de 72 kD révelée par immunomarquage ainsi que des modifications morphologiques des neurones et des cellules gliales, ainsiqu’un oedème périvasculaire et des ruptures de la myeline. le prétraitement des animaux avec des antagonistes du récepteurs de la 5-HT2 tels que la cyproheptadine et la kétansérine réduit les phénomènes de rupture de la BHE, de formation d’oedème et d’augmentation du flux sanguin cérébral. Ces prétraitements ne semblent par contre pas modifier l’expression de la HSP ou les lésions cellulaires d’une manière aussi nette. Ces résultats suggèrent que la 5-HT, via les récepteurs 5-HT2 des cellules endothéliales cérébrales, est impliquée dans la pathophysiologie de rupture de la BHE conduisant à des lésions cérébrales dans ce modèle de stress a la chaleur.
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Sharma, H.S., Westman, J., Cervós-Navarro, J., Nyberg, F. (1996). A 5-HT2 Receptor-Mediated Breakdown of the Blood-Brain Barrier Permeability and Brain Pathology in Heat Stress. In: Couraud, PO., Scherman, D. (eds) Biology and Physiology of the Blood-Brain Barrier. Advances in Behavioral Biology, vol 46. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9489-2_20
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DOI: https://doi.org/10.1007/978-1-4757-9489-2_20
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