The influence of nicotine on local cerebral blood flow in rats.

Local cerebral blood flow (LCBF) was measured in conscious rats during an acute nicotine infusion. LCBF was measured using the autoradiographic iodoantipyrine method. LCBF was unchanged in most brain structures during nicotine infusion compared to controls. Significant (P less than 0.05) increases were found in 3 structures (lateral geniculate body, superior colliculus, anteroventral nucleus of the thalamus). These structures have already shown increases in local glucose utilization in a previous study [2]. The observed increases in LCBF are interpreted to be secondary to metabolic activation by nicotine indicating the lack of a direct action of nicotine on cerebral blood vessels.     

Endothelial injury following experimental subarachnoid hemorrhage in rats: Effects on brain blood flow

Background: The leading cause of death and disability in patients suffering from aneurysmal subarachnoid hemorrhage (SAH) is cerebral vasospasm, a persistent, progressive, and often irreversible constriction of cerebral arteries. A wide array of pathological changes occur in cerebral arteries following SAH, with endothelial injury being the earliest and most consistent one. Since intact endothelium modulates many reflexes that influence vascular tone, damage to them may represent a significant contributor to cerebral vasospasm. Methods: Changes in local cerebellar blood flow (LCBF) and pathological alterations in major cerebral arteries were studied and compared in rats at various time intervals following SAH. SAH induced by the subarachnoid injection of 0.3 ml of whole blood. Sham rats received a subarachnoid injection of 0.3 ml of isotonic saline. Results: Except for an immediate but transient decrease, LCBF remained unchanged over a 3 day period following saline injection. Likewise, there were no pathological alterations in cerebral arteries of saline-injected rats. In contrast, the subarachnoid injection of whole blood produced significant changes in both LCBF and cerebral arteries. Within 30 minutes postblood injection, LCBF became significantly decreased and remained so for 4 hours. However, within 24 hours, LCBF had returned to control levels where it remained for 3 days. Endothelial injury was observed in the basilar and middle cerebral arteries from 30 minutes through 4 hours, the same periods in which LCBF was significantly reduced. Within 24 hours, the time period in which LCBF had rebounded to control ranges, cerebral arteries showed no evidence of endothelial damage and resembled control cells. Conclusion: The results indicate a direct correlation between changes in LCBF and the structural integrity of endothelial cells in the early stages following SAH. The lack of chronically depressed LCBF (after 1 day) may be related to the quick structural repair of endothelium. © 1994 Wiley-Liss, Inc.     

Stress and local cerebral blood flow: studies on restrained and unrestrained rats

Summary The degree of stress has been compared between two protocols used for the measurement of local cerebral blood flow (LCBF) in conscious rats. The first method involved acute surgical procedures (cannulation of both femoral veins and arteries) under halothane anesthesia. It was followed by a recovery period (2–3 h) during which the rat was before LCBF measurement. The second method employed chronic cannulation of the abdominal aorta and vena cava, allowing the LCBF assays to be performed on freely moving rats. Plasma corticosterone and a glucose tolerance tests showed that the freely moving rats were less stressed than the gently restrained ones. The LCBF of the two groups were not significantly different except in the frontal and parietal cortex, where it was more elevated in the freely moving rats. LCBF may be sensitive to the environmental conditions in freely moving rats whereas these vascular effects may be reduced after 2–3 h of gentle restraint. The two protocols tested in this study could be considered as good methods for studying LCBF in conscious rats, although some stress remained in gently restrained rats. Freely moving rats can be used for behavioural studies providing that the time lag of the arterial samples is taken into account. Since the basal LCBF values of gently restrained rats are minimally affected by the stress inherent in the preparation, this convenient protocol could be considered as useful for numerous investigations.     

Overall open-loop gain of rapidly acting arterial pressure control system in rabbits

Norepinephrine was infused intravenously in two groups of normal, awake rats. In one group local cerebral glucose utilization (LCGU) was measured by the deoxyglucose method (Sokoloff et al. 1977b); in the other group local cerebral blood flow (LCBF) was determined by the iodoantipyrine method (Sakurada et al. 1978). The experiments were performed during a stable state in which the heart rate was reduced between 36% (LCGU experiments) and 27% (LCBF experiments). Norepinephrine infusion reduced LCGU in all 39 structures measured between - 18 and - 37% from control values obtained in a group of normal non-infused rats. The decrease in LCGU was significant (P less than 0.05) in 38 of the 39 structures tested. LCBF was increased but not statistically significantly in most of the structures examined. When the LCGU values of the various structures during norepinephrine infusion were correlated with their corresponding LCBF values, a tight correlation (r = 0.94) was found indicating a close coupling between LCGU and LCBF during norepinephrine infusion. When compared to the relationship between LCGU and LCBF in a normal, non-infused control group, the slope of the regression line was increased significantly (P less than 0.01) by the norepinephrine infusion, indicating a resetting of the coupling mechanism. This means that, at a given metabolic rate, a higher blood flow is needed to perfuse a brain structure during norepinephrine infusion than during control conditions.     

Cerebral blood flow and histopathological changes following permanent bilateral carotid artery ligation in Wistar rats

Summary Cerebral blood flow and histopathological changes after bilateral carotid artery ligation (BCAL) in Wistar rats were studied. Eight of the 38 rats (21%) died within one week. In the 30 survivors, the incidence of histopathological change was 90% in the caudate nucleus, 23% in the cortex, 30% in the hippocampus, and 0% in the other structures. Local cerebral blood flow (LCBF) was measured using the quantitative autoradiographic ¹⁴C-iodoantipyrine technique in 24 anatomically discrete regions of the brain. BCAL induced ischemia in the entire forebrain. The percent reduction of LCBF was between 25–94% of the control at 2.5 h after BCAL. LCBF tended to recover 1 week after BCAL except for the regions of neuronal damage. These results suggest that neuronal damage does not correlate with the flow rate. In the present study, selective neuronal damage was also observed in rats with chronic cerebral ischemia.     

Local cerebral glucose utilisation following acute and chronic bilateral carotid artery ligation in Wistar rats: relation to changes in local cerebral blood flow

The effects on local cerebral blood flow (LCBF) and glucose utilisation (LCGU) of permanent, bilateral carotid artery ligation (BCAL) were studied in conscious Wistar rats. LCBF and LCGU were measured using quantitative autoradiographic ¹⁴C-iodoantipyrine and the ¹⁴C-2-deoxyglucose (¹⁴C-DG) techniques in 24 anatomically discrete regions of the brain. LCBF in the cerebral hemispheres 2.5 h (acute) after BCAL significantly decreased to 25–87% of the sham control, with the exception of the mammillary body. After acute BCAL, there was a heterogeneous accumulation of ¹⁴C-DG in the caudate nucleus and cerebral cortices. Only in the lateral geniculate body did LCGU significantly decrease after BCAL. One week (chronic) later, LCBF was significantly decreased in 15 (containing the caudate nucleus and all the cerebral cortices) of 24 structures. LCGU in ten (containing the caudate nucleus and all the cerebral cortices) of 24 structures after chronic BCAL significantly decreased to 66–77% of the sham control, except for regions with neuronal damage in which there was a heterogeneous uptake of ¹⁴C-DG. The ratio of LCBF/ LCGU in chronic BCAL was unchanged in comparison with values in the corresponding sham-operated group. This model of acute and chronic cerebral ischaemia, with impairment in cerebral circulation and/or glucose metabolism, is expected to become a pertinent tool for the neurophysiologist.     

Local cerebral blood flow velocity in newborn rats in normocapnia and hypercapnia

The local cerebral blood flow (LCBF) in the caudate nucleus was investigated in experiments on unanesthetized newborn rats by determing the rate of hydrogen saturation of the brain tissue and the cerebral blood volume was studied by plethysmography. LCBF in newborn animals was found to be considerably lower than in adults. Inhalation of CO₂ by newborn, unlike by adult rats, did not cause an increase in LCBF and the cerebral blood volume also remained unchanged.Laboratory of Brain Development, Scientific-Research Institute of Pediatrics, Academy of Medical Sciences of the USSR. (Presented by Academician M. Ya. Studenikin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 8, pp. 139–141, August, 1977.     

Stimulus frequency dependence of the linear relationship between local cerebral blood flow and field potential evoked by activation of rat somatosensory cortex

We investigated the relationship between evoked local cerebral blood flow (LCBF) and the field potential induced by somatosensory activation. The specific aim of the present study was to examine the correlation between variations of evoked LCBF and field potential when the stimulus duration was changed, and the dependency of the correlation on stimulus frequency. Evoked LCBF was measured using laser-Doppler flowmetry and the field potential was observed using a tungsten electrode inserted into the cortex alpha-chloralose-anesthetized rats. The cortex was activated by electrical stimulation of the hind paw with a 1.5 mA pulse (0.1 ms) applied at frequencies of 0.5, 1, 5 and 10 Hz for durations of 2, 5, 8, 10 or 15s. We extended our previous finding [Neurosci. Res. 40 (2001) 281-290], that both the magnitude of evoked LCBF (integrated LCBF) and the summed field potential (SigmaFP) exhibited a maximum at a stimulus frequency of 5 Hz to five different stimulus durations. Moreover, although variations of integrated LCBF and SigmaFP induced by changes in the stimulus duration were linearly correlated, the slope of the regression line depended on the stimulus frequency. This stimulus frequency dependence of the integrated LCBF-SigmaFP linear relationship may be because the vessel response is frequency dependent.     

The effects of HA1077, a novel protein kinase inhibitor,on reductions of cerebral blood flow and glucose metabolism following acute and/or chronic bilateral carotid artery ligation in Wistar rats

The effects of HA1077, a novel protein kinase inhibitor on local cerebral blood flow (LCBF) 2.5 h (acute) after permanent bilateral carotid artery ligation (BCAL) and on LCBF and local cerebral glucose utilisation (LCGU) one week (chronic) after BCAL were studied in conscious Wistar rats. Use was made of quantitative autoradiographic ¹⁴C-iodoantipyrine and the ¹⁴C-2-deoxyglucose techniques and 24 anatomically discrete regions of the brain. HA1077 (1 or 3 mg/kg) or saline was infused i.v. over a 30 min period. HA1077 significantly increased LCBF after acute BCAL in one of the 23 decreased regions in rats given 1 mg/kg, and in 14 of 23 decreased regions in rats given 3 mg/kg, compared to findings in the saline-treated group. Significant increases in LCBF and LCGU after chronic BCAL were noted in seven of the 13 decreased regions and in four of the 11 decreased regions in rats given 3 mg/kg, as compared to observations in the corresponding saline-treated group, respectively. The LCBF and LCGU reductions in forebrain regions with global ischaemia after acute and/or chronic BCAL were overcome by HA1077. These results suggest that HA1077 may be considered for treatment of subjects with acute and chronic cerebral ischaemia, with impairment in cerebral circulation and/or glucose metabolism.     

Changes in red blood cell behavior during cerebral blood flow increase in the rat somatosensory cortex: a study of laser-Doppler flowmetry

The purpose of this study was to investigate red blood cell (RBC) behavior during an increase in local cerebral blood flow (LCBF). We measured changes in RBC behavior by using laser-Doppler flowmetry (LDF) in alpha-chloralose-anesthetized rats. An increase in LCBF was carried out by approximately 2.5 and 4.0% CO(2) inhalation and activation of the somatosensory cortex. The activation of the cortex was induced by electrical stimulation of the hind paw with 1.5-mA pulses (0.1 ms) applied at frequencies of 0.2, 1, 5, and 10 Hz for a 5 s duration. The increases in LCBF and RBC velocity during both CO(2) inhalations were larger than that in RBC concentration (p < 0.05). LCBF and RBC velocity during 4.0% CO(2) inhalation were larger than those during 2.5% CO(2) inhalation (p < 0.05), though there was no significant difference in RBC concentration between the two conditions, suggesting a limitation of capillary volume. During somatosensory stimulation, the evoked LCBF increased with increasing stimulus frequency up to 5 Hz and decreased at 10 Hz. The responses of RBC concentration at 0.2 and 10 Hz were greater than those of RBC velocity (p < 0.05), but no significant differences in response magnitude were found at 1 and 5 Hz between RBC concentration and RBC velocity. These results suggest that the increase in LCBF during neuronal activity is different from that of controlling the LCBF as induced by CO(2), and that the regulation of RBC concentration and RBC velocity is controlled by independent mechanisms.     

Frequency dependence of local cerebral blood flow induced by somatosensory hind paw stimulation in rat under normo- and hypercapnia

We measured the field potential and the changes in local cerebral blood flow (LCBF) response during somatosensory activation (evoked LCBF) in alpha-chloralose--anesthetized rats by laser-Doppler flowmetry under normocapnia (PaCO(2)=34.3+/-3.8 mmHg) and hypercapnia (PaCO(2)=70.1+/-9.8 mmHg). Somatosensory activation was induced by electrical stimulation (0.2, 1, and 5 Hz with 1.5 mA for 5 s) of the hind paw. The neuronal activity of the somatosensory area of the hind paw was linear to the stimulus frequency, and there was no significant difference in the neuronal activity between hypercapnia and normocapnia. The baseline level of LCBF under hypercapnia was about 72.2% higher than that under normocapnia (p<0.01). The absolute response magnitude under hypercapnia was greater than that under normocapnia (p<0.05). The evoked LCBF under both conditions showed a frequency-dependent increase in the 0.2 to 5 Hz range, and the difference in the absolute response magnitude at the same stimulus frequency between normocapnia and hypercapnia became large with increasing stimulus frequency (p<0.05). On the other hand, after normalization to each baseline level there was no significant difference in the response magnitude of the normalized evoked LCBF between normocapnia and hypercapnia, indicating that the normalized evoked LCBF reflects neuronal activity even when the baseline LCBF was changed by the PaCO(2) level. The peak time and termination time of LCBF response curves with respect to the graded neuronal activity at 1 and 5 Hz stimulation increased significantly under hypercapnia, compared with those under normocapnia (p<0.05), although the rise time of 0.5 s was nearly constant. In conclusion, the results suggest a synergistic effect of the combined application of graded neuronal stimuli and hypercapnia on the LCBF response.     

Nanomolar concentrations of propranolol inhibit GABA-stimulated benzodiazepine binding to rat cerebral cortex

The influence of propranolol on GABA-stimulated [3H]diazepam binding in the rat cerebral cortex was investigated. Maximum potentiation of GABA-stimulated binding (20.6 +/- 4.5%, P less than 0.05) was observed at 100 microM propranolol, whilst maximum inhibition (32.5 +/- 2.5%, P less than 0.01) was observed at 1 nM propranolol. Low concentrations (1 nM) of (+)-propranolol were observed to be equipotent with (+/-)-propranolol in shifting the dose-response curve of GABA-stimulated [3H]diazepam binding by approximately 1/2 log unit. The phenomenon does not therefore show the stereospecificity observed towards either beta-adrenergic receptors or 5-hydroxytryptamine receptors.     

Nonlinear correlation between field potential and local cerebral blood flow in rat somatosensory cortex evoked by changing the stimulus current

The relationship between local cerebral blood flow (LCBF) and field potential (FP) evoked by hindpaw stimulation in rat somatosensory cortex has been investigated while changing stimulus current. The change in LCBF was measured using laser-Doppler flowmetry and the field potential was acquired using a tungsten electrode inserted into the cortex of alpha-chloralose-anesthetized rats. The cortex was activated by electrical stimulation of the hind paw with 5 Hz pulses (0.1 ms) applied at currents of 1.0, 1.5, 2.0 and 2.5 mA for 5 s. It was found that the summed FP is nonlinear with respect to stimulus current, whereas the integrated LCBF response is linear across the range of currents used in the experiment. This means that the relationship between the summed FP and integrated LCBF is nonlinear as a function of stimulus current.     

Neuroprotective effects of the novel brain-penetrating antioxidant U-101033E and the spin-trapping agent α-phenyl-N-tert-butyl nitrone (PBN)

Literature on the therapeutic efficacy of free radical scavengers suggests that drugs that are able to cross the blood-brain barrier are more effective in protecting the brain from ischemic damage. However, the exact mechanisms by which brain-penetrating antioxidants act have yet not been delineated. We compared the neuroprotective potential of the newly discovered pyrrolopyrimidine U-101033E with that of α-phenyl-N-tert-butyl nitrone (PBN) and investigated their influence on cerebral blood flow. Thirty male Sprague-Dawley rats were subjected to 90 min of middle cerebral artery (MCA) occlusion by an intraluminal filament. Local cerebral blood flow (LCBF) was bilaterally recorded by laser Doppler flowmetry. Neurological deficits were quantified daily. Infarct volume was assessed after 7 days. MCA occlusion reduced ipsilateral LCBF to 20–30% of baseline. After reperfusion, postischemic hyperemia was followed by a decrease in LCBF to about 70% of baseline. There was no difference in LCBF among groups. U-101033E improved neurological function and reduced infarct volume by 52% (P<0.05). Improvement of neurological function and reduction of infarct volume (–25%) in animals treated with PBN was not significant. We conclude that U-101033E has superior neuroprotective properties compared with PBN. Neither drug improves blood flow during ischemia and 1 h of reperfusion. The mechanisms by which these brain-penetrating antioxidants act remain to be clarified. Received: 17 March 1999 / Accepted: 12 July 1999     

Regional cerebral blood flow in acute hypertension induced by adrenaline, noradrenaline and phenylephrine in the conscious rat

Hypertension was induced in conscious rats by intravenous infusion of phenylephrine (3, 6 or 12 micrograms kg-1 min-1), noradrenaline (3 micrograms min-1) or adrenaline (3 micrograms kg-1 min-1). Local cerebral blood flow was measured autoradiographically in 24 defined brain structures using [14C]iodoantipyrine as the diffusible tracer. The mean arterial pressure induced by adrenaline, noradrenaline and the two higher doses of phenylephrine was 158-168 mmHg with no significant differences between the groups. Only adrenaline significantly increased local cerebral blood flow in nine of the 24 structures studied. The smaller capacity for autoregulation after adrenaline compared with other drugs might be related to a beta-adrenoreceptor-stimulating effect.     

The Effects of Fentanyl and Morphine on Local Blood Flow and Oxygen Tension in the Frontoparietal Cortex and Nucleus Accumbens of the Brain in White Rats

Studies on white rats showed that intraperitoneal administration of small doses of fentanyl (0.005 mg/kg) and morphine (1 mg/kg) decreased local blood flow and increased partial pressure of oxygen (pO2) in the frontoparietal area of the cerebral cortex but had the opposite effects in the nucleus accumbens--where there was a significant increase in local blood flow and just as significant a decrease in pO2. Analysis of the data led to the conclusion that these changes must result from significant changes in functional-metabolic activity in these structures, induced by intraperitoneal administration of fentanyl or morphine.     

GABA_A受体与地西泮的缺血后脑保护作用有关

研究GABAA受体是否参与地西泮的缺血后脑保护作用。SD雄性大鼠24只,用光化学法制作脑梗死模型。根据给药的不同将动物随机分为4组,每组6只。地西泮组腹腔注射地西泮10mg/kg;地西泮+bicuculline组腹腔注射地西泮10mg/kg和bicuculline2.1mg/kg;bicuculline组腹腔单独注射bicuculline2.1mg/kg;对照组腹腔注射等量的生理盐水。从术前24h开始注射,每8h一次,直至处死。术后动物存活24h,然后在深麻下灌流固定、取脑、切片。在Nissl染色的切片上计算最大脑梗死面积,用TUNEL染色计数梗死区凋亡细胞数。地西泮组最大脑梗死面积和TUNEL阳性细胞数明显少于其它三组(P<0.01)。地西泮的脑保护作用可被GABAA受体拮抗剂bicuculline部分抵消,因而地西泮可能部分通过GABAA受体发挥脑保护作用。     

Nitric oxide and the cerebral-blood-flow response to somatosensory activation following deafferentation

The single-vibrissa stimulation model in the rat was utilized to study the microvascular coupling between functional activation and local cerebral blood flow (LCBF) in both normal cortex and in cortex that had been peripherally deafferented. In addition, the role of chronic nitric oxide synthase (NOS) inhibition on the LCBF response to vibrissa stimulation was examined. One-day-old rats underwent deafferentation of all vibrissae on one side of the face, sparing C3, and received daily administration of either saline or N^ω-nitro-l-arginine (l-NA). After seven weeks of treatment, LCBF was measured autoradiographically in conscious rats with [¹⁴C]N-isopropyl-p-iodoamphetamine while C3 was stimulated bilaterally. Stimulation produced a greater increase in LCBF in the deafferented cortex of both the saline (30.4%) and l-NA treated (25.7%) animals than in the intact cortex (19.9% and 16%, respectively). The area of activation of LCBF (0.176 mm²) was comparable to the area metabolically activated (0.149 mm²), and the increase in area of LCBF activation following deafferentation (169%) was smaller than the increase in area that was metabolically activated (287%). Chronic inhibition of NOS did not alter the spatial extent of the blood-flow response. Received: 24 November 1998 / Accepted: 26 June 1999     

Modulation of evoked cerebral blood flow under excessive blood supply and hyperoxic conditions

We measured the field potential and local cerebral blood flow (LCBF) using laser-Doppler flowmetry in alpha-chloralose anesthetized rats during activation of the somatosensory cortex by electrical stimulation of the hind paw under independent administration of additional carbon dioxide and oxygen. The aim of this study was to test the hypothesis that the increase in LCBF during activation of the cortex (evoked LCBF) is not directed toward supplying oxygen for oxidative metabolism. Under the hypercapnic condition (PaCO(2) = 74. 9 +/- 14.3 mmHg), the baseline LCBF was about 46.5% higher than that under the normocapnic condition (PaCO(2) = 35.7 +/- 2.1 mmHg) (p < 0. 001), but after normalization for each baseline (divided by the prestimulus level), there was no significant difference in the peak value and the rise time of normalized evoked LCBF. On the other hand, the baseline level of LCBF under the hyperoxic condition (PaO(2) = 479.4 +/- 77.2 mmHg) was about 5.0% lower than that under the normoxic condition (PaO(2) = 105.5 +/- 7.8 mmHg) (p < 0.01), suggesting mild vasoconstriction under the condition of hyperoxia at rest. The peak value of normalized evoked LCBF under the hyperoxic condition was about 6.5% higher than that under the normoxic condition (p < 0.05). In addition, the rise time of evoked LCBF was earlier under the hyperoxic condition (0.37 +/- 0.16 s) than that under the normoxic condition (0.52 +/- 0.12 s) (p < 0.01). The field potential measured during stimulation under hypercapnic and hyperoxic conditions was not significantly different when compared with that under normal gas conditions. These results support our hypothesis and suggest that the excess oxygen is involved in the mechanism underlying the regulation of LCBF.