RESUMEN
Spatial learning is known to depend on protein synthesis in the hippocampus. Whereas the role of the hippocampus in spatial memory is established, the biochemical and molecular mechanisms underlying this process are poorly understood. To comprehend the complex pattern of protein expression induced by spatial learning, we analyzed alterations in the rat hippocampus proteome after 7 days of spatial learning in the Morris water maze. Forty Wistar rats were randomized into two groups. Animals of group A learned to localize a hidden platform in the water maze. Animals of group B served as controls and spent exactly the same time in the water maze as animals of group A. However, no platform was used in this test and the rats could not learn to localize the target. After the last trial, hydrophilic proteins from the hippocampus were isolated. A proteome-wide study was performed, based on two-dimensional gel electrophoresis and mass spectrometry. Compared with non-learning animals, 53 (70%) proteins were downregulated and 23 (30%) proteins were upregulated after 7 days in rats with spatial learning. The overall changes in protein expression, as quantified by the induction factor, ranged from -1.62 (downregulation to 62%) to 2.10 (upregulation by 110%) compared with controls (100%). Most identified proteins exhibit known functions in vesicle transport, cytoskeletal architecture, and metabolism as well as neurogenesis. These findings indicate that learning in the Morris water maze has a morphological correlate on the proteome level in the hippocampus.
Asunto(s)
Aprendizaje Discriminativo/fisiología , Hipocampo/metabolismo , Aprendizaje por Laberinto/fisiología , Proteínas del Tejido Nervioso/metabolismo , Animales , Regulación hacia Abajo , Perfilación de la Expresión Génica , Masculino , Proteómica , Distribución Aleatoria , Ratas , Ratas Wistar , Percepción Espacial/fisiología , Conducta Espacial/fisiología , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Volatile anesthetics can alter cardiac gene and protein expression. Of those underlying molecular changes in gene and protein expression in the myocardium after exposure to volatile anesthetics that have been identified, some of them have been related to cardioprotection. METHODS: We used two-dimensional gel electrophoresis and mass spectrometry to identify changes in the protein expression of the left ventricle myocardium of anesthesized rats. We maintained anesthesia for 3 h using isoflurane, sevoflurane or desflurane, respectively, at 1.0 minimum alveolar concentration (MAC) and dissected the left ventricular myocardium either immediately or 72 h after the end of anesthesia. RESULTS: We found changes of at least twofold in 106 proteins of the more than 1.600 protein spots discriminated in each gel. These differentially expressed proteins are associated with functions in glycolysis, mitochondrial respiration and stress response. No obvious difference could be observed between the patterns of differential expression of the three volatile anesthetics. CONCLUSION: We provide the first study of post-anesthetic protein expression profiles associated with three common volatile anesthetics. These volatile anesthetics promote a distinct change in the myocardial protein expression profile, whereby changes in the expression pattern still exist 72 h after anesthesia. These proteome changes are closely related to cardioprotection and ischemic preconditioning, indicating a common functional signaling of volatile anesthestics.
Asunto(s)
Anestésicos por Inhalación/farmacología , Miocardio/metabolismo , Proteínas/metabolismo , Animales , Cardiotónicos/farmacología , Desflurano , Electroforesis en Gel Bidimensional , Ventrículos Cardíacos , Isoflurano/análogos & derivados , Isoflurano/farmacología , Masculino , Espectrometría de Masas , Éteres Metílicos/farmacología , Ratas , Ratas Wistar , SevofluranoRESUMEN
The key goal in the treatment of acute ischemic stroke is fast vessel recanalization. Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is efficient in humans but mean time for recanalization is within hours. Ultrasound bio-effects has been shown to facilitate rt-PA mediated thrombolysis in peripheral arteries. We used an embolic stroke model in the rat. In all rats we induced an ischemic stroke by a selective occlusion of the middle cerebral artery with whole blood clots. From an entire collective of 54 rats 47 completed the protocol (n = 7 died early). Four different groups (no treatment n = 6; full dose rt-PA treatment only [10 mg/kg per body weight] n = 14, half dose rt-PA treatment plus ultrasound n = 10, and full dose rt-PA treatment plus ultrasound n = 17) were investigated. We found a significant reduction of absolute as well as relative infarct volume in the full dose rt-PA plus ultrasound group (81+/-72 mm(3); P< 0.05) in comparison to untreated rats (253+/-159 mm(3); P < 0.05) as well as in comparison to rats treated with full dose rt-PA only (167+/-91 mm(3); P < 0.05). There were five intracranial bleedings giving a bleeding rate of 9.3%. In summary: ultrasound treatment in addition to rt-PA is more effective than single rt-PA treatment in reducing infarct volume and safe with regard to bleeding.
Asunto(s)
Hipoxia-Isquemia Encefálica/terapia , Infarto de la Arteria Cerebral Media/terapia , Terapia Trombolítica/métodos , Terapia por Ultrasonido/métodos , Animales , Terapia Combinada , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Hipoxia-Isquemia Encefálica/patología , Hipoxia-Isquemia Encefálica/fisiopatología , Infarto de la Arteria Cerebral Media/patología , Infarto de la Arteria Cerebral Media/fisiopatología , Infarto de la Arteria Cerebral Media/prevención & control , Hemorragia Posoperatoria/prevención & control , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Proteínas Recombinantes de Fusión/farmacología , Terapia Trombolítica/tendencias , Activador de Tejido Plasminógeno/farmacología , Resultado del Tratamiento , Terapia por Ultrasonido/tendenciasRESUMEN
BACKGROUND AND OBJECTIVE: Acute isovolaemic haemodilution increases local and mean cerebral blood flow. It is not known whether a single haemodilution has a short-term effect only or whether it affects cerebral perfusion over a longer time period. In the present study, local and mean cerebral blood flow were determined in conscious rats after a 4, 24 and 48 h period following one-time haemodilution. METHODS: Thirty-six rats were randomized to three untreated sham groups and three groups of haemodilution (4, 24 or 48 h, n = 6 for each group). Isovolaemic haemodilution with albumin 5% aimed to a target haematocrit of 0.2. Local cerebral blood flow was measured in 38 brain regions by the iodo-[14C]antipyrine method in conscious normothermic rats. RESULTS: Isovolaemic haemodilution reduced haematocrit from 0.44 to 0.20. During the following 24 and 48 h periods, haematocrit remained low (0.22 and 0.21). Mean cerebral blood flow was similar in untreated sham groups (88 +/- 12 after 4 h, 92 +/- 11 after 24 h, 96 +/- 10 mL 100 g(-1) min(-1) after 48 h). Haemodilution increased mean cerebral blood flow after 4h (184 +/- 11 mL 100 g(-1) min(-1)), after 24h (153 +/- 13 mL 100 g(-1) min(-1)) and 48h (149 +/- 15 mL 100 g(-1) min(-1)) (P < or = 0.05). Local cerebral blood flow increased in all 38 structures after 4h haemodilution but decreased with time in six of 38 brain structures after 24h and in 15 regions after 48 h (P < or = 0.05). CONCLUSIONS: A single one-time haemodilution increased mean cerebral blood flow for 2 days. However, local adaptation of cerebral blood flow to a chronic low haematocrit occurred but was heterogeneous within the brain.
Asunto(s)
Antipirina/análogos & derivados , Circulación Cerebrovascular/fisiología , Hemodilución/efectos adversos , Animales , Autorradiografía , Glucemia/metabolismo , Presión Sanguínea/fisiología , Volumen Sanguíneo/fisiología , Frecuencia Cardíaca/fisiología , Hematócrito , Concentración de Iones de Hidrógeno , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
The present study addresses the question whether local glucose transport kinetics are correlated with local glucose transporter densities in the brain. In 47 brain structures the local rate constants for 3-O-[(14)C]methylglucose (3-O-MG) transport, K(1) and k(2,) were quantified, and local glucose Glut1 and Glut3 transporter densities were determined by immuno-autoradiographic methods. Statistically significant correlations were found between the rate constants for glucose transport and the transporter densities. The correlations were tighter for Glut1 than for Glut3. Inasmuch as 3-O-MG is transported by the same transporter as glucose, these results indicate that the local densities of glucose transporters determine local glucose transport rates in the brain.
Asunto(s)
3-O-Metilglucosa/farmacocinética , Encéfalo/metabolismo , Proteínas de Transporte de Monosacáridos/metabolismo , Proteínas del Tejido Nervioso , Animales , Autorradiografía , Química Encefálica/fisiología , Transportador de Glucosa de Tipo 1 , Transportador de Glucosa de Tipo 3 , Masculino , Proteínas de Transporte de Monosacáridos/análisis , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: The hypothesis of a compensatory dilation of cerebral vessels to maintain cerebral blood flow at a high blood viscosity was tested during hypercapnia in the study after replacement of blood by hemoglobin solutions of defined viscosities. If compensatory vasodilation exists at normocapnia at a high blood viscosity, vasodilatory mechanisms may be exhausted when hypercapnia is added, resulting in a lack of increase in cerebral blood flow at hypercapnia. METHODS: In conscious rats, blood was replaced by ultrapurified cross-linked hemoglobin solutions that had defined and shear rate-independent low or high viscosities (low- and high-viscosity groups). Blood viscosity differed threefold between both groups (1.2 vs. 3.6 mP x s). Thereafter, rats inhaled either a normal or an increased concentration of carbon dioxide in air. Cerebral blood flow was determined by the iodo[14C]antipyrine method. RESULTS: During normocapnia, global and local cerebral blood flows did not differ between both groups. With increasing degrees of hypercapnia, global and local cerebral blood flows were gradually elevated in the low-viscosity group (2.8 ml x mmHg(-1) CO2 x 100 g(-1) x min(-1)), whereas they remained unchanged in the high-viscosity group. CONCLUSIONS: Changes in blood viscosity do not result in changes of cerebral blood flow as long as cerebral vessels can compensate for these changes by vasodilation or vasoconstriction. However, such vascular compensatory adjustments may be exhausted in their response to further pathophysiologic conditions in blood vessels that have already been dilated or constricted as a result of changes in blood viscosity.
Asunto(s)
Antipirina/análogos & derivados , Viscosidad Sanguínea/fisiología , Circulación Cerebrovascular/fisiología , Recambio Total de Sangre , Hipercapnia/fisiopatología , Animales , Análisis de los Gases de la Sangre , Dióxido de Carbono/sangre , Dióxido de Carbono/metabolismo , Hemodinámica/fisiología , Hemoglobinas/metabolismo , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Glucose, the major fuel in the brain, is transported across the cell membranes by facilitated diffusion mediated by glucose transporter proteins. Essentially two types of glucose transporters are localized in the membranes of brain endothelial cells, astrocytes, and neurons. Their densities are well adjusted to changes in local energy demand.
Asunto(s)
Encéfalo/metabolismo , Metabolismo Energético/fisiología , Glucosa/metabolismo , Proteínas de Transporte de Monosacáridos/metabolismo , Animales , HumanosRESUMEN
We addressed the question to which extent cerebral blood flow (CBF) is maintained when, in addition to a high blood viscosity (Bvis) arterial oxygen content (CaO2) is gradually decreased. CaO2) was decreased by hemodilution to hematocrits (Hct) of 30, 22, 19, and 15% in two groups. One group received blood replacement (BR) only and served as the control. The second group received an additional high viscosity solution of polyvinylpyrrolidone (BR/PVP). Bvis was reduced in the BR group and was doubled in the BR/PVP. Despite different Bvis, CBF did not differ between BR and BR/PVP rats at Hct values of 30 and 22%, indicating a complete vascular compensation of the increased Bvis at decreased CaO2. At an Hct of 19%, local cerebral blood flow (LCBF) in some brain structures was lower in BR/PVP rats than in BR rats. At the lowest Hct of 15%, LCBF of 15 brain structures and mean CBF were reduced in BR/PVP. The resulting decrease in cerebral oxygen delivery in the BR/PVP group indicates a global loss of vascular compensation. We concluded that vasodilating mechanisms compensated for Bvis increases thereby maintaining constant cerebral oxygen delivery. Compensatory mechanisms were exhausted at a Hct of 19% and lower as indicated by the reduction of CBF and cerebral oxygen delivery.
Asunto(s)
Antipirina/análogos & derivados , Viscosidad Sanguínea/fisiología , Encéfalo/irrigación sanguínea , Encéfalo/metabolismo , Arterias Cerebrales/metabolismo , Oxígeno/metabolismo , Povidona/análogos & derivados , Animales , Transporte Biológico/efectos de los fármacos , Transporte Biológico/fisiología , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Velocidad del Flujo Sanguíneo/fisiología , Viscosidad Sanguínea/efectos de los fármacos , Encéfalo/efectos de los fármacos , Circulación Cerebrovascular/efectos de los fármacos , Circulación Cerebrovascular/fisiología , Hematócrito , Masculino , Povidona/farmacología , Ratas , Ratas Sprague-Dawley , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología , VigiliaRESUMEN
BACKGROUND: The effects of xenon inhalation on mean and local cerebral blood flow (CBF) and mean and local cerebral glucose utilization (CGU) were investigated using iodo-[14C]antipyrine and [14C]deoxyglucose autoradiography. METHODS: Rats were randomly assigned to the following groups: conscious controls (n = 12); 30% (n = 12) or 70% xenon (n = 12) for 45 min for the measurement of local CBF and CGU; or 70% xenon for 2 min (n = 6) or 5 min (n = 6) for the measurement of local CBF only. RESULTS: Compared with conscious controls, steady state inhalation of 30 or 70% xenon did not result in changes of either local or mean CBF. However, mean CBF increased by 48 and 37% after 2 and 5 min of 70% xenon short inhalation, which was entirely caused by an increased local CBF in cortical brain regions. Mean CGU determined during steady state 30 or 70% xenon inhalation remained unchanged, although local CGU decreased in 7 (30% xenon) and 18 (70% xenon) of the 40 examined brain regions. The correlation between CBF and CGU in 40 local brain structures was maintained during steady state inhalation of both 30 and 70% xenon inhalation, although at an increased slope at 70% xenon. CONCLUSION: Effects of 70% xenon inhalation on CBF in rats are time-dependent. During steady state xenon inhalation (45 min), mean values of CBF and CGU do not differ from control values, and the relation of regional CBF to CGU is maintained, although reset at a higher level.
Asunto(s)
Anestésicos por Inhalación/farmacología , Circulación Cerebrovascular/efectos de los fármacos , Glucosa/metabolismo , Xenón/farmacología , Animales , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
The endothelial surface layer (glycocalyx) of cerebral capillaries may increase resistance to blood flow. This hypothesis was investigated in mice by intravenous administration of heparinase (2500 IU/kg body weight in saline), which cleaves proteoglycan junctions of the glycocalyx. Morphology was investigated by transmission electron microscopy. Cerebral perfusion velocity was recorded before and during heparinase or saline treatment using laser-Doppler flowmetry. In addition, cerebral blood flow (CBF) was measured 10 minutes after heparinase or saline treatment using the iodo[14C]antipyrine method. Laser-Doppler flowmetry and CBF measurements were performed during normocapnia and severe hypercapnia (PCO2: 120 mm Hg). After heparinase, morphology showed a reduced thickness of the glycocalyx in cortical microvessels by 43% (P < 0.05) compared with saline-treated controls. Under normocapnic conditions, a 15% (P < 0.05) transient increase of cerebral flow velocity occurred 2.5 to 5 minutes after heparinase injection. Laser-Doppler flow and CBF returned to control values ten minutes after the injection. However, during severe hypercapnia, heparinase treatment resulted in a persisting increase in laser-Doppler flow (6%, P < 0.05) and CBF (30%, P < 0.05). These observations indicate the existence of a flow resistance in cerebral capillaries exerted by the glycocalyx. The transient nature of the CBF increase during normocapnia may be explained by a vascular compensation that is exhausted during severe hypercapnia.
Asunto(s)
Circulación Cerebrovascular/fisiología , Endotelio Vascular/fisiología , Glicocálix/fisiología , Adaptación Fisiológica/fisiología , Animales , Antiinflamatorios no Esteroideos/farmacocinética , Antipirina/farmacocinética , Encéfalo/irrigación sanguínea , Encéfalo/fisiología , Capilares/efectos de los fármacos , Capilares/fisiología , Radioisótopos de Carbono , Glicocálix/ultraestructura , Liasa de Heparina/farmacología , Hipercapnia/metabolismo , Hipercapnia/fisiopatología , Flujometría por Láser-Doppler , Ratones , Ratones Endogámicos BALB C , Microscopía ElectrónicaRESUMEN
That cerebral blood flow remains unchanged at an increased blood viscosity, as long as the vascular supply is not compromised, was tested. To induce a reduced blood supply of some parts of the brain and to keep the supply unchanged in others both carotid arteries were occluded in anesthetized, ventilated rats. By this procedure, blood supply to the rostral brain, but not to the brainstem and cerebellum, was compromised. Blood viscosity was increased by intravenous infusion of 20% polyvinylpyrrolidone (high viscosity group) or decreased by infusion of 5% albumin (low viscosity group). Cerebral blood flow was measured by the [14C]iodoantipyrine method in 50 complete coronal sections of the rostral brain and 22 complete coronal sections of the brainstem and cerebellum in each rat. In the high viscosity group, mean cerebral blood flow of the rostral brain was significantly lower (46 +/- 7 mL/100 g(-1) x min(-1)) than in the low viscosity group (82 +/- 18 mL/100 g(-1) x min(-1)). No differences could be observed in brainstem and cerebellum between both groups (162 +/- 29 mL/100 g(-1) x min(-1) vs. 156 +/- 18 mL/100 g(-1) x min(-1)). Local analysis of cerebral blood flow in different brain structures of the coronal sections showed the same identical results; i.e., in 29 of the 31 brain structures analyzed in rostral brain, local cerebral blood flow was lower in the high viscosity group, whereas no differences could be observed in the 11 brain structures analyzed in the brainstem and cerebellum. It is concluded that under normal conditions cerebral blood flow can be maintained at an increased blood viscosity by a compensatory vasodilation. When the capacity for vasodilation is exhausted by occlusion of supplying arteries, an increased blood viscosity results in a decrease of cerebral blood flow.
Asunto(s)
Viscosidad Sanguínea/fisiología , Enfermedades de las Arterias Carótidas/fisiopatología , Circulación Cerebrovascular/fisiología , Bulbo Raquídeo/irrigación sanguínea , Prosencéfalo/irrigación sanguínea , Animales , Arteriopatías Oclusivas/fisiopatología , Autorradiografía , Velocidad del Flujo Sanguíneo/fisiología , Hematócrito , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND AND PURPOSE: The effects of hypothermia on global cerebral blood flow (CBF) and glucose utilization (CGU) have been extensively studied, but less information exists on a local cerebral level. We investigated the effects of normothermic and hypothermic anesthesia on local CBF (LCBF) and local CGU (LCGU). METHODS: Thirty-six rats were anesthetized with isoflurane (1 MAC) and artificially ventilated to maintain normal PaCO(2) (alpha-stat). Pericranial temperature was maintained normothermic (37.5 degrees C, n=12) or was reduced to 35 degrees C (n=12) or 32 degrees C (n=12). Pericranial temperature was maintained constant for 60 min until LCBF and LCGU were measured with autoradiography. Twelve conscious rats served as normothermic control animals. RESULTS: Normothermic anesthesia significantly increased mean CBF compared with conscious control animals (29%, P<0.05). Mean CBF was reduced to control values with mild hypothermia and to 30% below control animals with moderate hypothermia (P<0.05). Normothermic anesthesia reduced mean CGU by 44%. No additional effects were observed during mild hypothermia. Moderate hypothermia resulted in a further reduction in mean CGU (41%, P<0.05). Local analysis showed linear relationships between LCBF and LCGU in normothermic conscious (r=0.93), anesthetized (r=0.92), and both hypothermic groups (35 degrees C r=0. 96, 32 degrees C r=0.96, P<0.05). The LCBF-to-LCGU ratio increased from 1.5 to 2.5 mL/micromol during anesthesia (P<0.05), remained at 2.4 mL/micromol during mild hypothermia, and decreased during moderate hypothermia (2.1 mL/micromol, P<0.05). CONCLUSIONS: Anesthesia and hypothermia induce divergent changes in mean CBF and CGU. However, local analysis demonstrates a well-maintained linear relationship between LCBF and LCGU during normothermic and hypothermic anesthesia.
Asunto(s)
Encéfalo/metabolismo , Circulación Cerebrovascular , Metabolismo Energético , Glucosa/metabolismo , Hipotermia Inducida , Equilibrio Ácido-Base , Anestesia General , Anestesia por Inhalación , Animales , Autorradiografía , Temperatura Corporal , Dióxido de Carbono/sangre , Estado de Conciencia , Isoflurano , Masculino , Oxígeno/sangre , Presión Parcial , Ratas , Ratas Sprague-DawleyAsunto(s)
Apoptosis , Isquemia Encefálica/patología , Isquemia Encefálica/fisiopatología , Animales , Humanos , NecrosisRESUMEN
Whereas acute hyperglycemia has been shown to result in an unchanged local cerebral glucose utilization (LCGU) the changes of LCGU during chronic hyperglycemia are a matter of dispute. The present study had three aims: (1) To compare the effects of acute and chronic hyperglycemia on LCGU and to investigate in vivo the lactate level as a potential indicator of glycolytic flux. (2) To investigate local changes in brain Glut1 and/or Glut3 glucose transporter densities during chronic hyperglycemia. (3) To analyze the relationship between LCGU and local Glut densities during chronic hyperglycemia. To induce chronic hyperglycemia in rats steptozotocin was given i.p. and experiments were performed 3 weeks later. LCGU was measured by the 2-[14C]deoxyglucose method and intraparenchymal lactate concentration by MR-spectroscopy. Local densities of the glucose transport proteins were determined by immunoautoradiographic methods. During chronic hyperglycemia weighted average of LCGU increased by 13.9% whereas it remained unchanged during acute hyperglycemia. The cerebral lactate/choline ratio was increased by 143% during chronic hyperglycemia. The average density of glucose transporters Glut1 decreased by 7.5%. Local densities of Glut1 were decreased in 12 of 28 brain structures. Glut3 remained unchanged. Positive correlations were found between LCGU and local Glut densities during control conditions and during chronic hyperglycemia. It was concluded that (1) Chronic, but not acute hyperglycemia is followed by an increased LCGU. (2) The capacity to transport glucose is decreased during chronic hyperglycemia. (3) Increased LCGU and decreased densities of Glut1 are matched on a local level.
Asunto(s)
Encéfalo/metabolismo , Glucosa/metabolismo , Hiperglucemia/metabolismo , Proteínas de Transporte de Monosacáridos/metabolismo , Proteínas del Tejido Nervioso , Animales , Autorradiografía , Química Encefálica/fisiología , Circulación Cerebrovascular/fisiología , Enfermedad Crónica , Transportador de Glucosa de Tipo 1 , Transportador de Glucosa de Tipo 3 , Espectroscopía de Resonancia Magnética , Masculino , Proteínas de Transporte de Monosacáridos/análisis , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Hypothermia may interfere with the relationship between cerebral blood flow (CBF) and metabolism. Because this conclusion was based on the analysis of global values, the question remains whether hypothermic CBF/metabolism uncoupling exists on a local cerebral level. This study investigated the effects of hypothermic anesthesia on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU). METHODS: Thirty-six rats were anesthetized with isoflurane (1 minimum alveolar concentration) and artificially ventilated to maintain normal arterial carbon dioxide partial pressure (pH-stat). Pericranial temperature was maintained as normothermic (37.5 degrees C, n = 12) or was reduced to 35 degrees C (n = 12) or 32 degrees C (n = 12). Pericranial temperature was maintained constant for 60 min until LCBF or LCGU were measured by autoradiography. Twelve conscious rats served as normothermic controls. RESULTS: Compared with conscious animals, mean CBF remained unchanged during normothermic anesthesia. Mean CBF significantly increased during mild hypothermia but was unchanged during moderate hypothermia. During normothermic anesthesia, mean CGU was 45% lower than in conscious controls (P < 0.05). No further CGU reduction was found during mild hypothermia, whereas CGU further decreased during moderate hypothermia (48%; P < 0.05). Local analysis showed a linear LCBF/LCGU relationship in conscious (r = 0.94) and anesthetized (r = 0.94) normothermic animals, as well as in both hypothermic groups (35 degrees C: r = 0.92; 32 degrees C: r = 0.95; P < 0.05). The LCBF-to-LCGU ratio increased from 1.4 (conscious controls) to 2.4 (normothermic isoflurane) and 3.6 ml/micromol (mild and moderate hypothermia, P < 0.05). CONCLUSIONS: Decrease of mean CGU at unchanged or increased mean CBF during hypothermic anesthesia may not indicate uncoupling. Local analysis shows a maintained linear relationship that is reset to a higher CBF/CGU ratio.
Asunto(s)
Química Encefálica/fisiología , Circulación Cerebrovascular/fisiología , Hipotermia/metabolismo , Hipotermia/fisiopatología , Equilibrio Ácido-Base , Anestesia por Inhalación , Anestésicos por Inhalación , Animales , Autorradiografía , Glucosa/metabolismo , Isoflurano , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: It is not known whether the effects of desflurane on local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) are different from those of other volatile anesthetics. METHODS: Using the autoradiographic iodoantipyrine and deoxyglucose methods, LCGU, LCBF, and their overall means were measured in 60 Sprague-Dawley rats (10 groups, n = 6 each) during desflurane and isoflurane anesthesia and in conscious controls. RESULTS: During anesthesia, mean cerebral glucose utilization was decreased compared with conscious controls: 1 minimum alveolar concentration (MAC) desflurane: -52%; 1 MAC isoflurane: -44%; 2 MAC desflurane: -62%; and 2 MAC isoflurane: -60%. Local analysis showed a reduction of LCGU in the majority of the 40 brain regions analyzed. Mean cerebral blood flow was increased: 1 MAC desflurane: +40%; 1 MAC isoflurane: +43%; 2 MAC desflurane and 2 MAC isoflurane: +70%. LCBF was increased in all brain structures investigated except in the auditory cortex. No significant differences (P < 0.05) could be observed between both anesthetics for mean values of cerebral glucose use and blood flow. Correlation coefficients obtained for the relation between LCGU and LCBF were as follows: controls: 0.95; 1 MAC desflurane: 0.89; 2 MAC desflurane: 0.60; 1 MAC isoflurane: 0.87; and 2 MAC isoflurane: 0.68. CONCLUSION: Differences in the physicochemical properties of desflurane compared with isoflurane are not associated with major differences in the effects of both volatile anesthetics on cerebral glucose utilization, blood flow, and the coupling between LCBF and LCGU.
Asunto(s)
Anestesia por Inhalación , Anestésicos por Inhalación/farmacología , Encéfalo/efectos de los fármacos , Circulación Cerebrovascular/fisiología , Glucosa/metabolismo , Isoflurano/análogos & derivados , Animales , Análisis de los Gases de la Sangre , Presión Sanguínea/efectos de los fármacos , Encéfalo/metabolismo , Desflurano , Isoflurano/farmacología , Masculino , Alveolos Pulmonares/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Nonischemic brain capillaries show a continuous and heterogeneous plasma perfusion. In the current study, plasma perfusion was investigated in rats during 2 to 168 hours of permanent middle cerebral artery occlusion. Perfused capillaries were detected in brain cryosections by fluorescein isothiocyanate (FITC) dextran after 10 minutes of circulation time. Heterogeneity of capillary perfusion was identified by Evans blue (EB), which circulated for 3 seconds. In this setting, the heterogeneity of intracapillary EB concentrations reflects heterogeneities in capillary flow velocities. The CBF was quantified by simultaneous iodo[14C]antipyrine autoradiography. When moving from normal flow to low-flow areas in the ischemic hemisphere, three states of capillary filling could be distinguished: state 1--fast perfusion, filling by FITC dextran and EB (CBF 0.33 mL x g(-1) x min(-1)); state 2--delayed perfusion, only FITC dextran filling (CBF 0.104 mL x g(-1) x min(-1)); state 3--minimal perfusion, no dye filling (CBF 0.056 mL x g(-1) x min(-1)). In tissue of state 1 at the borderline to ischemic tissue, a higher heterogeneity of intracapillary EB concentration (85.7%) was found than in the contralateral nonischemic hemisphere (76.4%) (P < 0.05), indicating a compromised microcirculation. The adjacent ischemic areas were filled by FITC dextran (state 2) 2 to 4 hours after middle cerebral artery occlusion, indicating a maintained, although slow, perfusion at this time. Later, minimal perfused areas (state 3) progressively replaced the delayed perfused areas (state 2). This study shows, for the first time, the evolution of microvascular disturbances in relation to CBF. In the low-flow areas, an early residual plasma perfusion is later followed by a lack of perfusion or minimal perfusion. In areas of higher, although reduced flow at the border between normal and ischemic tissue, an extreme capillary perfusion heterogeneity indicates permanent microcirculatory abnormalities.
Asunto(s)
Encéfalo/irrigación sanguínea , Capilares/fisiopatología , Circulación Cerebrovascular/fisiología , Microcirculación/fisiopatología , Arteria Cerebral Media/lesiones , Animales , Antipirina/farmacocinética , Autorradiografía , Radioisótopos de Carbono , Lateralidad Funcional , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
After 3 days of water deprivation, the following parameters were measured in rats: (i) brain water content (apparent diffusion coefficient); (ii) local cerebral glucose utilization (LCGU) ([14C]deoxyglucose method) and (iii) densities of glucose transporters Glut1 and Glut3 (immunoautoradiography). The results show that brain water content is maintained after water deprivation. Densities of glucose transporters Glut1 and Glut3 increased in parallel to increased LCGU in some of the osmoregulatory structures indicating a long-term local adaptation of glucose transporters to LCGU.
Asunto(s)
Agua Corporal/metabolismo , Encéfalo/metabolismo , Desoxiglucosa/metabolismo , Glucosa/metabolismo , Proteínas de Transporte de Monosacáridos/metabolismo , Proteínas del Tejido Nervioso , Privación de Agua/fisiología , Animales , Autorradiografía , Presión Sanguínea , Transportador de Glucosa de Tipo 1 , Transportador de Glucosa de Tipo 3 , Frecuencia Cardíaca , Imagen por Resonancia Magnética , Masculino , Especificidad de Órganos , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Tritio , Equilibrio HidroelectrolíticoRESUMEN
The predictive value of transcranial Doppler (TCD) cerebral blood flow velocity (CBFV) measurements for cerebral blood flow (CBF) calculations in humans is still controversial, and experimental correlative studies are lacking. The aim of the present study was to validate TCD signals of CBFV during focal cerebral ischemia. Therefore, CBFV determined in the middle cerebral artery (MCA) was compared with values of CBF obtained from autoradiograms of ischemic brain areas. To determine CBFV, a transcranial Doppler ultrasound probe (TCD) adapted to small sample volumes was used in 9 rabbits. CBF was quantified after a final infusion of [14C]-iodoantipyrine in the same animals. For focal cerebral ischemia induction, two threads were flushed upward simultaneously into the internal carotid artery, resulting in a flow reduction in the ipsilateral MCA. After thread occlusion, mean systolic CBFV in the MCA decreased from 49 +/- 9 cm/s to 22 +/- 3 cm/s. CBF in the caudate nucleus was reduced (19 +/- 8 mL/100 g/min) compared to the contralateral nonischemic side (52 +/- 18 mL/100 g/min). The decrease in hemispheric CBF correlated well with the decrease in both mean systolic (r = 0.97) and diastolic (r = 0.94) CBFV in the MCA (p < 0.01). The decrease in CBFV determined by transcranial Doppler ultrasound in the MCA appears to reflect the reduction in CBF in the affected brain hemisphere and can be used as a quantitative in vivo parameter for tissue perfusion.