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  • Title: Effects of N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine on the blood-brain barrier permeability in the rat.
    Author: Deli MA, Németh L, Falus A, Abrahám CS.
    Journal: Eur J Pharmacol; 2000 Jan 03; 387(1):63-72. PubMed ID: 10633162.
    Abstract:
    Histamine plays a role in the regulation of the blood-brain barrier function. In this study, effects of N, N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine (DPPE), an intracellular histamine binding site antagonist on the cerebrovascular permeability were investigated in control and post-ischemic male Wistar rats. Intravenous administration of DPPE, in a dose of 1 and 5 mg/kg, was not followed by any major clinical change, but 20 mg/kg proved to be toxic. A significantly (P<0.05) increased permeability for sodium fluorescein (MW=376) was seen in hippocampus, striatum, and cerebellum, but not in parietal cortex, of rats 2 h after the injection of 5 mg/kg DPPE, whereas no increase was measured later. There was a more intense (5- to 12-fold) and prolonged elevation in Evan's blue-labeled albumin (MW=67,000) extravasation 2, 4, and 8 h after 5 mg/kg DPPE administration in each brain region. In parietal cortex, a dose-dependent increase in albumin extravasation developed 4 h after intravenous injection of 1, 5, and 20 mg/kg DPPE, but doses applied resulted in no significant change in sodium fluorescein permeability. Cerebral ischemia-reperfusion evoked by four-vessel occlusion caused a significant (P<0.05) increase in the permeability for albumin in each region, but few changes in that of sodium fluorescein. DPPE treatment failed to prevent the ischemia-reperfusion-induced changes in the blood-brain barrier permeability. In conclusion, DPPE induced an increased permeability in the rat, which supports a role for histamine, as an intracellular messenger, in the regulation of the blood-brain barrier characteristics.
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