The influence of nimodipine on cerebral blood flow autoregulation and blood-brain barrier

1988 ◽  
Vol 69 (6) ◽  
pp. 919-922 ◽  
Author(s):  
Hans-Georg Höllerhage ◽  
Michael R. Gaab ◽  
Matthias Zumkeller ◽  
Gerhard F. Walter

✓ Twenty anesthetized rats were randomly assigned to a nimodipine-treated group or a control group of 10 rats each. Local cerebral blood flow (lCBF) was measured by means of a surface electrode using the hydrogen clearance technique. Systemic arterial pressure (SAP) was varied with administration of norfenefrine or by hemorrhage in order to obtain SAP/cerebral blood flow (CBF) curves under different conditions. In the control group, a typical autoregulation curve was obtained with an lCBF plateau between 70 and 120 mm Hg SAP. The nimodipine-treated animals, however, showed only a slight diminution in the slope of the curve but no real plateau, indicating impairment of CBF autoregulation. In another series, 20 anesthetized rats were randomly assigned to a treatment group or a control group of 10 animals each. Intravenous Evans blue dye was used as a tracer for blood-brain barrier (BBB) function. In both groups, SAP was raised to a level of 180 mm Hg with administration of norfenefrine for 6 minutes. Extravasation of significantly more Evans blue dye was observed in the nimodipine group than in the control group, indicating impairment of the BBB. It is concluded that nimodipine may impair CBF autoregulation, allowing damage to the BBB under hypertensive conditions.

1985 ◽  
Vol 5 (2) ◽  
pp. 275-281 ◽  
Author(s):  
William M. Pardridge ◽  
Gary Fierer

The literature regarding the blood–brain barrier (BBB) transport of butanol is conflicting as studies report both incomplete and complete extraction of butanol by the brain. In this work the BBB transport of both [14C]butanol and [3H]water was studied using the carotid injection technique in conscious and in ketamine- or pentobarbital-anesthetized rats employing N-isopropyl- p-[125I]iodoamphetamine ([125I]IMP) as the internal reference and as a fluid microsphere. The three isotopes (3H, 125I, 14C) were conveniently counted simultaneously in a liquid scintillation spectrometer. IMP is essentially completely sequestered by the brain for at least 1 min in conscious rats and for 2 min in anesthetized animals. Butanol extraction by rat forebrain is not flow limited but ranges between 77 ± 1 and 87 ± 1% for the three conditions. The incomplete extraction of butanol by the forebrain is due to diffusion restriction of butanol clearance in some regions (frontal cortex, colliculi) but not in others (caudate, hippocampus, olfactory bulb). The permeability-surface area product/cerebral blood flow ratio of butanol and water in rat forebrain remains relatively constant, 1.7 ± 0.2 and 1.0 ± 0.1, respectively, despite a twofold increase in cerebral blood flow in conscious relative to pentobarbital-anesthetized rats. The absence of an inverse relationship between flow and butanol or water extraction is consistent with capillary recruitment being the principal mechanism underlying changes in cerebral blood flow in anesthesia. The diffusion restriction of BBB transport of butanol in some regions, but not in others, necessitates a careful regional analysis of BBB permeability to butanol prior to usage of this compound as a cerebral blood flow marker.


1984 ◽  
Vol 4 (1) ◽  
pp. 96-102 ◽  
Author(s):  
R. Suzuki ◽  
C. Nitsch ◽  
K. Fujiwara ◽  
I. Klatzo

Interrelationship between the breakdown of the blood–brain barrier (BBB) to Evans blue and elevations in the regional cerebral blood flow (rCBF) was studied in rabbits subjected to adrenaline- or metaraminol-induced systemic hypertension and also in bicuculline-induced seizures. The rCBF was assessed in small samples from various regions of the brain with the use of [3H]nicotine, and the permeability of the BBB was evaluated with an Evans blue tracer. In acute hypertension, Evans blue extravasations were observed in the occipital cortex and sometimes in the superior colliculus, i.e., the regions which also showed the highest elevations in rCBF. The breakdown of the BBB in acute hypertension was clearly related to the rate of mean arterial blood pressure rise, being much less pronounced in the metaraminol group, which showed a much slower blood pressure elevation rate. In bicuculline-induced seizures, there was no evident correlation between the amplitude of rCBF elevations and Evans blue extravasations. Preservation of BBB integrity was observed in areas showing high elevations in the rCBF.


2019 ◽  
Vol 126 (1) ◽  
Author(s):  
Mariana Pereira de Souza Goldim ◽  
Amanda Della Giustina ◽  
Fabricia Petronilho

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Rong Pan ◽  
Kewei Yu ◽  
Theodore Weatherwax1 ◽  
Handong Zheng ◽  
Yirong Yang ◽  
...  

Background and Purpose: Fear of symptomatic intracerebral hemorrhage (ICH) has been the primary reason for withholding tPA thrombolysis from acute ischemic stroke patients. Early blood brain barrier (BBB) damage is appreciated to be closely associated with post-thrombolysis ICH, while it remains a technical challenge for rapid assessment of BBB damage before tPA administration. Our recent data showed that cerebral ischemia induced rapid degradation of tight junction protein occludin in ischemic cerebromicrovessels. This study further investigates whether the cleaved occludin is released into the blood stream and how blood occludin levels correlate to the extent of ischemic BBB damage. Methods: Male Sprague Dawley rats were subjected to 1.5, 3, 4.5, 12 and 24 hours of middle cerebral artery occlusion (MCAO), followed by 5-min reperfusion. Blood samples were taken before and after MCAO. Blood occludin was assessed by ELISA. BBB permeability was measured by Evans blue dye leakage. Occludin cleavage was identified on immunoblots. Results: MCAO induced Evans blue dye leakage and blood occludin increase in a duration-dependent manner. Blood occludin increase concurrently occurred with the loss of occludin from ischemic cerebral microvessels. Western blot analysis identified two cleaved occludin fragments (31- and 55- kDa) in the blood. Lastly, blood occludin levels remained significantly higher than its basal level within the first 24 hours after MCAO onset. Conclusions: Our results indicate that blood occludin levels correlate well with the extents of BBB damage and thus may serve as a potential biomarker for evaluating the risk of hemorrhagic transformation before tPA administration.


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