Determination of rat brain buffering in vivo by 31P-NMR

1988 ◽  
Vol 64 (5) ◽  
pp. 1829-1836 ◽  
Author(s):  
S. Adler ◽  
V. Simplaceanu ◽  
C. Ho

Buffering capacity of most tissues is composed of both rapid and slow phases, the latter presumably due to active acid extrusion. To examine the time course of brain buffering the brain pH of Sprague-Dawley rats was measured using 31P-nuclear magnetic resonance. The effect on brain pH of 30- or 58-min exposures to 20% CO2 followed by 30- or 38-min recovery periods, respectively, was studied. Brain pH reached its lowest value after a 15-min exposure to elevated CO2, thereafter slowly and steadily increasing. During recovery brain pH rose rapidly in the first 5 min exceeding control brain pH by 0.08 pH units. Brain pH fell during the next 30 min despite increases in blood pH and decreases in blood CO2 tension. Calculated intrinsic brain buffering rose steadily threefold during the last 40 min of CO2 exposure and during the final 30 min of recovery. These data show that in rat brain there is a temporally late buffering process, most likely active acid extrusion, requiring greater than 30 min for full activation and at least 30 min for discontinuation.

1991 ◽  
Vol 11 (2) ◽  
pp. 236-241 ◽  
Author(s):  
Stephen C. Jones ◽  
Ender Korfali ◽  
Sam A. Marshall

The indicator fractionation technique using a diffusible indicator as a tracer for the determination of CBF has been used for numerous investigations of the cerebral circulation and its pathophysiology. The diffusible tracer is “trapped” in the brain based on the proper delay between tracer injection and cessation of the cerebral circulation by decapitation before the appearance of the tracer in the cerebral venous circulation. If this delay is too long, the quantitative assumption of the indicator fractionation technique will not be met, and CBF values will be underestimated. In 13 Sprague-Dawley rats anesthetized with pentobarbital, the appearance of [14C]iodoantipyrine at the torcular was assessed as a function of Paco2. An inverse linear relationship between Paco2 (in millimeters of mercury) and cerebral venous appearance, Ta (in seconds), was established with the regression equation Ta = −0.0842 · Paco2 + 12.3 ( R2 = 0.70, slope significantly different from zero, p < 0.001). Ta varied between 5 and 12 s and Paco2 varied between 84 and 18 mm Hg, respectively. Thus, in low-flow states, the decapitation time may be lengthened to 12 s, whereas in high-flow states, the time must be 5 s to eliminate the possibility of backflux of tracer out of the brain.


2015 ◽  
Vol 35 (3) ◽  
pp. 501-511 ◽  
Author(s):  
Jenny-Ann Phan ◽  
Anne M Landau ◽  
Dean F Wong ◽  
Steen Jakobsen ◽  
Adjmal Nahimi ◽  
...  

We quantified the binding potentials ( BPND) of [11C]yohimbine binding in rat brain to alpha-2 adrenoceptors to evaluate [11C]yohimbine as an in vivo marker of noradrenergic neurotransmission and to examine its sensitivity to the level of noradrenaline. Dual [11C]yohimbine dynamic positron emission tomography (PET) recordings were applied to five Sprague Dawley rats at baseline, followed by acute amphetamine administration (2 mg/kg) to induce elevation of the endogenous level of noradrenaline. The volume of distribution ( VT) of [11C]yohimbine was obtained using Logan plot with arterial plasma input. Because alpha-2 adrenoceptors are distributed throughout the brain, the estimation of the BPND is complicated by the absence of an anatomic region of no displaceable binding. We used the Inhibition plot to acquire the reference volume, VND, from which we calculated the BPND. Acute pharmacological challenge with amphetamine induced a significant decline of [11C]yohimbine BPND of ∼38% in all volumes of interest. The BPND was greatest in the thalamus and striatum, followed in descending order by, frontal cortex, pons, and cerebellum. The experimental data demonstrate that [11C]yohimbine binding is sensitive to a challenge known to increase the extracellular level of noradrenaline, which can benefit future PET investigations of pathologic conditions related to disrupted noradrenergic neurotransmission.


2003 ◽  
Vol 284 (6) ◽  
pp. H1942-H1948 ◽  
Author(s):  
M. Ursula Norman ◽  
Rebecca A. Lew ◽  
A. Ian Smith ◽  
Michael J. Hickey

Bradykinin is a vasoactive peptide that has been shown to increase the permeability of the cerebral microvasculature to blood-borne macromolecules. The two zinc metalloendopeptidases EC 3.4.24.15 (EP 24.15) and EC 3.4.24.16 (EP 24.16) degrade bradykinin in vitro and are highly expressed in the brain. However, the role that these enzymes play in bradykinin metabolism in vivo remains unclear. In the present study, we investigated the role of EP 24.15 and EP 24.16 in the regulation of bradykinin-induced alterations in microvascular permeability. Permeability of the cerebral microvasculature was assessed in anesthetized Sprague-Dawley rats by measuring the clearance of 70-kDa FITC dextran from the brain. Inhibition of EP 24.15 and EP 24.16 by the specific inhibitor N-[1-( R, S)-carboxy-3-phenylpropyl]-Ala-Aib-Tyr- p-aminobenzoate (JA-2) resulted in the potentiation of bradykinin-induced increases in cerebral microvessel permeability. The level of potentiation was comparable to that achieved by the inhibition of angiotensin-converting enzyme. These findings provide the first evidence of an in vivo role for EP 24.15/EP 24.16 in brain function, specifically in regulating alterations in microvessel permeability induced by exogenous bradykinin.


1976 ◽  
Vol 68 (2) ◽  
pp. 235-239 ◽  
Author(s):  
J. C. BUTTE ◽  
RYOKO KAKIHANA ◽  
E. P. NOBLE

SUMMARY In the present study the circadian changes which occur in the levels of corticosterone in the brain and plasma in Sprague–Dawley rats are reported. The levels of corticosterone in the brain were found to have a daily trough and crest with timing similar to that observed for the plasma steroid. In addition, the effect of histamine stress on the corticosterone content of the particulate and the soluble fractions at the trough and crest was examined. The levels of both brain fractions were significantly higher 20 min after histamine injection. The time of day at which the stress was applied was not a significant factor in the magnitude of the stress response.


2000 ◽  
Vol 88 (3) ◽  
pp. 1142-1149 ◽  
Author(s):  
Jazmir M. Hernandez ◽  
Mark J. Fedele ◽  
Peter A. Farrell

The temporal pattern for changes in rates of protein synthesis and glucose uptake after resistance exercise, especially relative to each other, is not known. Male Sprague-Dawley rats performed acute resistance exercise ( n = 7) or remained sedentary ( n = 7 per group), and the following were assessed in vivo 1, 3, 6, 12 and 24 h later: rates of protein synthesis, rates of glucose uptake, phosphatidylinositol 3-kinase (PI3-kinase) activity, and p70S6k activity. Rates of protein synthesis in mixed gastrocnemius muscle did not increase until 12 h after exercise (e.g., at 12 h, sedentary = 138 ± 4 vs. exercised = 178 ± 6 nmol phenylalanine incorporated ⋅ g muscle− 1 ⋅ h− 1, mean ± SE, P < 0.05), whereas at 6 h after exercise rates of glucose uptake were significantly elevated (sedentary = 0.18 ± 0.020 vs. exercised = 0.38 ± 0.024 μmol glucose 6-phosphate incorporated ⋅ kg muscle− 1 ⋅ min− 1, P < 0.05). At 24 h after exercise, rates of protein synthesis were still elevated, whereas glucose uptake had returned to basal levels. Arterial insulin concentrations were not different between groups at any time. Non-insulin-stimulated activities of PI3-kinase and p70S6k were higher at 6, 12, and 24 h after exercise ( P < 0.05), and, generally, these occurred when rates of protein synthesis (12 and 24 h) and glucose uptake were elevated (6 and 12 but not 24 h) by exercise. These data suggest that regulators of protein synthesis and glucose uptake may respond to the same contraction-generated signals with different kinetics or that they respond to different intra- or extracellular signals that are generated by exercise.


2012 ◽  
Vol 117 (6) ◽  
pp. 1128-1140 ◽  
Author(s):  
George K. Lewis ◽  
Zachary R. Schulz ◽  
Susan C. Pannullo ◽  
Teresa L. Southard ◽  
William L. Olbricht

Object In convection-enhanced delivery (CED), drugs are infused locally into tissue through a cannula inserted into the brain parenchyma to enhance drug penetration over diffusion strategies. The purpose of this study was to demonstrate the feasibility of ultrasound-assisted CED (UCED) in the rodent brain in vivo using a novel, low-profile transducer cannula assembly (TCA) and portable, pocket-sized ultrasound system. Methods Forty Sprague-Dawley rats (350–450 g) were divided into 2 equal groups (Groups 1 and 2). Each group was divided again into 4 subgroups (n = 5 in each). The caudate of each rodent brain was infused with 0.25 wt% Evans blue dye (EBD) in phosphate-buffered saline at 2 different infusion rates of 0.25 μl/minute (Group 1), and 0.5 μl/minute (Group 2). The infusion rates were increased slowly over 10 minutes from 0.05 to 0.25 μl/minute (Group 1) and from 0.1 to 0.5 μl/minute (Group 2). The final flow rate was maintained for 20 minutes. Rodents in the 4 control subgroups were infused using the TCA without ultrasound and without and with microbubbles added to the infusate (CED and CED + MB, respectively). Rodents in the 4 UCED subgroups were infused without and with microbubbles added to the infusate (UCED and UCED + MB) using the TCA with continuous-wave 1.34-MHz low-intensity ultrasound at a total acoustic power of 0.11 ± 0.005 W and peak spatial intensity at the cannula tip of 49.7 mW/cm2. An additional 4 Sprague-Dawley rats (350–450 g) received UCED at 4 different and higher ultrasound intensities at the cannula tip ranging from 62.0 to 155.0 mW/cm2 for 30 minutes. The 3D infusion distribution was reconstructed using MATLAB analysis. Tissue damage and morphological changes to the brain were assessed using H & E. Results The application of ultrasound during infusion (UCED and UCED + MB) improved the volumetric distribution of EBD in the brain by a factor of 2.24 to 3.25 when there were no microbubbles in the infusate and by a factor of 1.16 to 1.70 when microbubbles were added to the infusate (p < 0.001). On gross and histological examination, no damage to the brain tissue was found for any acoustic exposure applied to the brain. Conclusions The TCA and ultrasound device show promise to improve the distribution of infused compounds during CED. The results suggest further studies are required to optimize infusion and acoustic parameters for small compounds and for larger molecular weight compounds that are representative of promising antitumor agents. In addition, safe levels of ultrasound exposure in chronic experiments must be determined for practical clinical evaluation of UCED. Extension of these experiments to larger animal models is warranted to demonstrate efficacy of this technique.


1987 ◽  
Vol 26 (03) ◽  
pp. 131-134 ◽  
Author(s):  
S. Jinnouchi ◽  
K. Watanabe ◽  
T. Ueda ◽  
K. Kinoshita ◽  
T. Yamaguchi ◽  
...  

The biodistribution of N-isopropyl-p-iodoamphetamine (IMP) was studied in the rat brain.131 l-labelled IMP was injected intravenously in awake animals. Activities in the brain of Sprague-Dawley rats were 2.68–3.22 (% dose/g) in the cortex and 0.59–0.66 (% dose/g) in the white matter at 1 min p. i. Activities in the cortex were slightly increased at 60 min p. i., while activities in the white matter increased markedly at 60 min and 6 h p. i. Therefore, the cerebral cortex-to-white matter ratio decreased from 5 to 1 within 60 min after injection. Autoradiograms of the rat brain at 1–10 min p. i. showed high contrasts. Activities were high in the cortex and low in the white matter, but homogeneous at 60 min – 6 h. IMP seems to be a useful agent for cerebral perfusion imaging in the early phase after injection. Knowledge of biodistribution of this agent is considered to be indispensable for the interpretation of images.


1997 ◽  
Vol 273 (3) ◽  
pp. H1342-H1346 ◽  
Author(s):  
K. Toyoda ◽  
K. Fujii ◽  
S. Ibayashi ◽  
T. Kitazono ◽  
T. Nagao ◽  
...  

The basilar artery and its branch arterioles dilate actively in response to a marked decrease in blood pressure and maintain cerebral blood flow (CBF) to the brain stem. We tested the hypothesis that ATP-sensitive potassium (KATP) channels play a role in the autoregulatory responses of the brain stem circulation in vivo. In anesthetized Sprague-Dawley rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and branch arterioles were measured through a cranial window during stepwise hemorrhagic hypotension. During topical application of 10(-6) and 10(-5) mol/l of glibenclamide, a selective KATP-channel blocker, the lower limit of CBF autoregulation shifted upward to 60-75 from 30-45 mmHg in the vehicle group. Glibenclamide significantly impaired the dilator response of small arterioles (baseline diameter 45 +/- 2 microns) throughout hypotension (P < 0.03) but did not impair the dilatation of the basilar artery (247 +/- 3 microns) or large arterioles (99 +/- 4 microns). Thus KATP channels appear to play an important role in the regulation of CBF to the the brain stem during hypotension by mediating the compensatory dilatation of small arterioles. In contrast, these channels may not be a major regulator of the vascular tone of larger arteries during hypotension.


1984 ◽  
Vol 22 (01) ◽  
pp. 31-34 ◽  
Author(s):  
E. J. Knust ◽  
R. M. Baldwin ◽  
T. Chen ◽  
L. E. Feinendegen ◽  
H.-J. Machulla

SummaryGermanyFor the investigation of brain functions 18F-3-deoxy-3-fluoro-D-glucose (3-FDG) and N-isopropyl-p-123I-iodoamphetamine (IMP) were synthesized and the course of radioactivity measured in several organs of mice. The results can be summarized as follows:1.IMP is rapidly extracted from the blood and reaches a value of less than 1%/g within the first 15 min;2.123I-radioactivity in the lungs shows a maximum of 76%/g as soon as half a minute after injection and decreases with a concomitant increase in the liver and brain;3. The maximum 123I-uptake in the brain of 11%/g is reached after 30 min and levels off at a constant value of 10%/g;4. 30 min after injection the brain/ blood ratio for IMP is about 14;5. The time course of 3-FDG in the brain has a maximum of 4.8%/g as soon as 5 min after injection and decreases to a constant value of 3%/g within 1 hr; and6. Accumulation of 18F-radioactivity in the heart reaches a maximum of 14%/g after 1 hr and is eliminated with a half-life of 300 min. Comparative clinical studies with 3-FDG and 3-0-11C-methyl-D-glucose (ÇMG) have shown that 3-FDG can be considered as a CMG-analogue and thus can be used for the in-vivo determination of local glucose perfusion and transport rates.


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