Effect of up-regulation of NMDA receptors on cerebral O2 consumption and blood flow in rat

We tested the hypothesis that cerebrocortical blood flow and O₂ consumption would be proportional to an up-regulated number of functional N-methyl- -aspartate (NMDA) receptors. Previous work had shown a relationship between cerebral metabolism and NMDA receptor activity. We increased the specific binding to NMDA receptors in the cerebral cortex, from 2.2 ± 0.9 to 4.5 ± 0.8 (density units) in male Long-Evans rats by daily giving two intraperitoneal injections (30 mg/kg) of CGS-19755, an NMDA receptor inhibitor, for 7 consecutive days (discontinued for 20 h before experiment). Twelve up-regulated (CGS treated) and 12 control rats were used in this study. Under isoflurane anesthesia and after topical stimulation of the right cerebral cortex with 10⁻² M NMDA, the blood flow (¹⁴C-iodoantipyrine method) increased from 98 ± 11 ml/min/100 g in the unstimulated cortex of the control rats to 161 ± 37 ml/min/100 g in the stimulated cortex. The unstimulated value for blood flow (95 ± 7 ml/min/100 g) did not change in the upregulated group but it doubled (194 ± 69 ml/min/100 g) in the stimulated, upregulated cortex. Similarly, O₂ consumption (cryomicrospectrophotometrically determined) in normal rats increased 46%, from 9.3 ± 1 ml/min/100 g to 13.6 ± 4 after NMDA stimulation. While in the upregulated animals, O₂ consumption increased 103% from 7.9 ± 0.6 to 16 ± 6.5 after NMDA stimulation. In conclusion, NMDA receptor upregulation does not alter basal cerebrocortical blood flow or O₂ consumption but in the NMDA-stimulated cortex, the blood flow and O₂ consumption increase is dependent on the number of NMDA receptors present.     

Effect of nitroprusside on regional cerebral cyclic GMP, blood flow and O2 consumption in rat

This investigation was conducted to test whether topical nitroprusside (NP), a cytosolic guanylate cyclase activator, would increase the level of cyclic GMP and alter O₂ consumption or blood flow in the cerebral cortex of rats. Male Long-Evans rats were used in a control (n = 9), low dose NP (n = 13, 10⁻³ M) or high dose NP (n = 12, 10⁻² M) group. Nitroprusside or saline was topically applied to the right side of the cerebral cortex and the left side was used as a control. The cyclic GMP level was determined in five rats in each group using a radioimmunoassay. In the o ther rats in each group, regional cerebral blood flow was measured by [¹⁴C]iodoantipyrine and regional arterial and venous O₂ saturations were determined microspectrophotometrically. Nitroprusside significantly increased the cyclic GMP level from 21.4 ± 12.0 pmol/g (contralateral cortex) to 52.2 ± 36.7 pmol/g (NP treated cortex) in low dose nitroprusside group and from 19.9 ± 22.6 pmol/g (contralateral cortex) to 58.5 ± 15.1 pmol/g (NP treated cortex) in high dose nitroprusside group. High dose nitroprusside significantly increased cerebral blood flow from 80 ± 11 ml · min⁻¹ · 100 g (contralateral cortex) to 114 ± 11 ml · min⁻¹ · 100 g (NP treated cortex). However, there was no significant difference in O₂ extraction and O₂ consumption between the NP treated cortex and contralateral cortex in either the low or the high dose NP groups. In the high dose NP group, the O₂ extraction was 8.0 ± 1.3 ml O₂ · 100 ml⁻¹ in the treated cortex and 8.8 ± 1.5 ml O₂ · 100 ml⁻¹ in the contralateral cortex, while the O₂ consumptions in the NP treated cortex and contralateral cortex were 8.1 ± 1.3 ml O₂ · min⁻¹ · 100 g⁻¹ and 7.3 ± 1.2, respectively. Thus, NP increased the cyclic GMP level without a significant change in O₂ consumption in the cerebral cortex. Our data suggested that O₂ consumption in the cerebral cortex was not affected by the increased level of cyclic GMP.     

Global reduction in cerebral blood flow and metabolism elicited from intrinsic neurons of fastigial nucleus

We sought to determine whether the global increase in regional cerebral blood flow (rCBF) produced by electrical stimulation of the rostral cerebellar fastigial nucleus (FN) is a consequence of excitation of intrinsic neurons of the FN or of axons of fibers passing through or projecting into it. Studies were conducted in rats anesthetized with chloralose, paralyzed and ventilated. rCBF was measured with [¹⁴C]iodoantipyrine as tracer and regional cerebral glucose utilization (rCGU) by [¹⁴C]2-deoxyglucose in homogenates of 11 brain regions. Neuronal perikarya in FN were excited chemically by local microinjection of the glutamate analogue kainic acid (KA) (5 nmol in 100 nl). KA elicited a transient and significant fall of arterial pressure and heart rate, the fastigial depressor response (FDR). Associated was a significant and symmetrical reduction in rCBF, to 44% of control in all regions except medulla. The response was site- and agent-specific and unrelated to the hypotension. KA also significantly and proportionally reduced, to 52% of control, rCGU in the same 10 areas of brain. In all regions the magnitudes of the reductions in rCBF and rCGU elicited by KA were linearly related. Intrinsic neurons of FN were chronically destroyed by local microinjection of the excitotoxin ibotenic acid (IBO) (10 μg/μl in 0.4 μl). Destruction of intrinsic FN neurons had no effect on resting rCBF nor on the global cerebrovascular vasodilation elicited by electrical stimulation of the FN. We conclude that: (a) excitation of intrinsic neurons of FN elicits a widespread reduction of cerebral metabolism and, secondarily, blood flow; (b) FN neurons do not exert a long-term tonic influence on brain blood flow nor metabolism; (c) the global increase in rCBF elicited by electrical stimulation of the FN is a consequence of excitation of axons projecting into or through the nucleus.     

Effects of mild hypothermia on cerebral blood flow-independent changes in cortical extracellular levels of amino acids following contusion trauma in the rat

The mechanism of hypothermic cerebroprotection after traumatic brain injury (TBI) is unknown. The present study was conducted to investigate the effects of mild hypothermia on the changes in cortical extracellular amino acids and cerebral blood flow (CBF) caused by cerebral contusion created in the rat parietal cortex by a weight-drop method. CBF in both normothermia (37°C) and hypothermia (32°C) groups, which was monitored using the hydrogen clearance technique, decreased significantly after contusion, but never fell below the threshold for ischemia. Cortical levels of glutamate, aspartate, glycine and taurine, which were measured by intracerebral microdialysis, were significantly increased after contusion in each group. However, these increases were greater in the hypothermic than in the normothermic rats. Normal plasma amino acid levels were high, and autoradiography following intravenous injection of ¹⁴C-labeled glutamate revealed marked extravasation of [¹⁴C]glutamate at the site of cortical impact. These results suggest that the post-traumatic increase in extracellular amino acids occurs independently of CBF reduction, and that extravasation of amino acids from the vascular compartment partly contributes to this increase. Hypothermic cerebroprotection in TBI is thus likely to occur through a mechanism other than reduction in interstitial excitatory amino acids. In TBI, it is postulated that the postsynaptic effects of hypothermia may be more important than the presynaptic effects, when CBF is kept above the ischemic threshold.     

Regional cerebral blood flow and cerebrospinal fluid glutamate in leukoaraiosis

Cerebral blood flow and cerebrospinal fluid amino acids were investigated in patients with leukoaraiosis on magnetic resonance imaging. Ten patients with leukoaraiosis and without significant cerebral infarction and ten age-matched controls without abnormality on magnetic resonance imaging were studied. The regional cerebral blood flow was measured using the stable xenon computed tomography method. The blood flow was significantly lower in the leukoaraiosis area in the leukoaraiosis group than in the same area in the control group. The cerebrospinal fluid glutamate concentration was significantly higher in the leukoaraiosis group than in the control group. There was a significant negative correlation between the blood flow in the leukoaraiosis area and the cerebrospinal fluid glutamate concentration. The high concentration of cerebrospinal fluid glutamate in patients with leukoaraiosis is considered to be related to ischaemia. Received: 17 December 1997 Received in revised form: 14 April 1998 Accepted: 26 April 1998     

Cerebral O2 consumption in young Eker rats, effects of GABA blockade: implications for autism

Since there is a strong correlation between tuberous sclerosis and autism, we used a tuberous sclerosis model (Eker rat) to test the hypothesis that the increased regional cerebral O₂ consumption in the Eker rat might be associated with autism. We also examined whether this increased cerebral O₂ consumption was related to changes in the activity of the gamma-aminobutyric acid (GABA) inhibitory system. Young (4 weeks) male control Long Evans (n = 14) and Eker (n = 14) rats (70–100 g) were divided into control and bicuculline (1 mg/kg/min for 2 min then 0.1 mg/kg/min for 13 min, GABA_A receptor antagonist) treated animals. Cerebral regional blood flow (¹⁴C-iodoantipyrine) and O₂ consumption (cryomicrospectrophotometry) were determined in isoflurane anesthetized rats. We found significantly increased basal O₂ consumption in the cortex (6.3 ± 0.7 ml O₂/min/100 g Eker vs. 5.1 ± 0.2 ml O₂/min/100 g control), hippocampus and cerebellum, but not the pons. Regional cerebral blood flow was also elevated in the cortex and hippocampus in Eker rats at baseline, but cerebral O₂ extractions were similar. Bicuculline significantly increased O₂ consumption in the cortex (6.5 ± 0.3) and all other regions of the control rats, but had no effect on cortex (5.9 ± 1.5) or other regions of the Eker rats. Cerebral blood flow followed a similar pattern. In conclusion, Eker rats had significantly elevated cerebral O₂ consumption and blood flow, but this was not affected by GABA receptor blockade. This suggested a reduced activity of the GABA_A receptor in the brains of Eker rats. This may have important implications in the treatment of autism.     

AMPA receptors shape Ca2+ responses in cortical oligodendrocyte progenitors and CG-4 cells

Intracellular calcium signals triggered by glutamate receptor activation were studied in primary cortical oligodendrocyte lineage cells and in the oligodendrocyte cell line CG-4. Glutamate, kainate, and AMPA (30-300 μM) increased [Ca ²⁺]_i in both types of cells at the stage of oligodendrocyte progenitors (O-2A; GD3⁺) or pro-oligodendroblasts (04⁺). The peak amplitude of Ca²⁺ responses to glutamate receptor agonists was significantly larger in cortical cells. In CG-4 and in cortical cells, the majority (more than 90%) of bipolar GD3⁺ or multipolar 04⁺ cells responded to kamate. In all the cells analyzed, kainate was more efficacious than AMPA and glutamate. The percentage of bipolar or multipolar cells responding to glutamate was significantly lower in the CG-4 cell line than in primary cultures. Cellular responses typical of metabotropic glutamate receptor activation were observed in 20% of the cortical O-2A progenitors, but in none of the CG-4 cells. The AMPA-selective antagonist GYKI 52466 blocked kainate-induced Ca²⁺ responses in cortical O-2A cells. The selective AMPA receptor modulator cyclothiazide (30 μM) greatly potentiated the effects of AMPA (30-100 μM) on [Ca ²⁺]_i in cortical and CG-4 cells. Our findings indicate that Ca²⁺ responses in cells of the oligodendrocyte lineage are primarily shaped by functional AMPA receptors. © 1995 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

尼麦角林对偏头痛患者脑血流的影响

目的研究尼麦角林对成人偏头痛患者脑血流动力学的影响。方法156例偏头痛患者随机分为试验组（76例）和对照组（80例）,同时选择60例健康体检者作为健康对照组,试验组应用尼麦角林治疗,而对照组应用布洛芬治疗,应用经颅多普勒超声（TCD）技术检测试验组和对照组治疗前后及健康对照组双侧大脑中动脉、大脑前动脉、大脑后动脉的收缩期峰值血流变化。结果（1）156例偏头痛患者服药前头痛侧与非头痛侧比较,大脑中动脉、大脑前动脉、大脑后动脉的收缩期峰值血流速度（Vs）有显著差异;两组头痛侧之间及非头痛侧之间无显著性差异。治疗后比较,对照组差异明显,试验组无明显差异;两组头痛侧比较有显著性差异;（2）156倒患者服药前头痛侧大脑中动脉、大脑前动脉、大脑后动脉的收缩期峰值血流速度与健康对照组比较增快。治疗后：对照组变化不明显;试验组头痛侧大脑中动脉、大脑前动脉、大脑后动脉的收缩期峰值血流速度降低,且与健康对照组差异不明显。结论尼麦角林可明显改善偏头痛患者的脑血流,防止偏头痛的发作。     

Effects of brain stem stimulation on cortical NADH fluorescence, blood flow, and O2 consumption in the cat

A causal relationship has been suggested between the altered electrical cortical activity and the increases in both cortical metabolism and blood flow which follow experimental reticulocortical activation. To further study this hypothesis, cortical O₂ consumption, NADH fluorescence, and blood flow were monitored simultaneously with aortic blood pressure and ECoG after the electrical stimulation of the pontomesencephalic reticular formation (MRF) in anesthetized cats. Reversible increases in blood pressure, cortical blood flow, and O₂ consumption, and decreases in NADH fluorescence were induced by MRF stimulation. All these changes were linearly related to each other as a function of stimulus intensity; they were often but not always associated with an increase in the ECoG frequency. MRF stimulation after ganglionic suppression with hexamethonium chloride revealed a dissociation of the resulting changes in the ECoG from the changes in cortical blood flow and metabolism. In addition, pharmacologically induced acute elevations of blood pressure caused changes in the experimental parameters similar to those which followed MRF stimulation but without a significant effect on the ECoG. We conclude that (i) acute increases in cortical blood flow and oxidative metabolism after electrical MRF stimulation may be more related to the simultaneous elevations of blood pressure than to changes in the ECoG; and (ii) an acute increase in cortical blood flow may by itself stimulate cortical oxidative metabolism in the anesthetized cat.     

Influence of nimodipine on cerebral blood flow in human cerebral ischaemia

Summary Cerebral blood flow (CBF) was measured by xenon-133 inhalation and single photon emission computerized tomography (SPECT) in 7 patients with acute cerebral ischaemia prior to and 30 min after intravenous infusion of nimodipine (1 mg). Neurological examination, CT and CBF study were performed no later than 6 h after the onset of symptoms. Regional perfusion abnormalities were seen in all patients when the CT scan was still normal. Follow-up CT revealed low-density areas roughly corresponding to the core of the perfusion defect. Nimodipine infusion significantly decreased the mean arterial blood pressure (P<0.01), while PaCO₂ and clinical symptoms remained unchanged. A significant CBF improvement (P<0.05) after nimodipine was seen in the border zone of the ischaemic infarct but not in the core of the lesion or in the unaffected contralateral hemisphere.     

应激对大鼠海马谷氨酸、天冬氨酸和γ-氨基丁酸含量的影响

目的　探讨应激对大鼠海马谷氨酸、天冬氨酸和γ 氨基丁酸 (GABA)含量的动态影响。方法　将 72只健康雄性大鼠随机分为 5个应激暴露不同时间组和对照组 ,每组 12只。利用高效液相色谱仪 紫外检测法 ,分别于应激第 1,3,7,14和 2 8天观察应激对大鼠海马谷氨酸、天冬氨酸及GABA含量的影响。结果　应激第 1天组大鼠海马谷氨酸和天冬氨酸含量与对照组相比 ,差异无显著性 ;但GABA含量 [(2 74 7± 0 339) μmol/g]低于对照组 [(3 719± 0 5 2 8) μmol/g;P <0 0 5 ]。应激第 3,7,14和 2 8天组谷氨酸含量 [分别为 (7 818± 0 799) μmol/g ,(9 0 0 7± 0 5 2 0 ) μmol/g,(8 0 4 9± 0 733) μmol/g和 (8 12 9± 1 5 5 6 ) μmol/g]高于对照组 [(6 4 11± 0 6 38) μmol/g];天冬氨酸含量 [分别为 (2 717± 0 2 5 8)μmol/g,(2 6 96± 0 317) μmol/g,(2 82 8± 0 4 6 8) μmol/g和 (4 6 4 9± 0 6 37) μmol/g]也高于对照组 [(2 0 0 3± 0 2 71) μmol/g];均P <0 0 1。应激第 14天组和 2 8天组GABA含量 [分别为 (4 4 6 2± 0 883) μmol/g和(4 4 97± 0 85 7) μmol/g]高于对照组 (P <0 0 5～0 .0 0 1) ,应激第 3天组和 7天组的GABA含量与对照组间的差异无显著性。结论　应激第 3天开始     

血液光量子疗法对局灶性脑缺血大鼠大脑皮层局部血流量和脑水肿的影响

本文动态观测了光量子疗法治疗血栓栓塞性脑缺血大鼠,大脑皮层局部血流量(rCBF)及脑水肿的变化。结果:缺血6小时经光量子血液治疗2小时后,rCBF于注后30min明显增加,达19.78％(P<0.01),以后各点维持在一定水平,2小时增加到19.30(P<0.05)。脑组织比重:缺血中心区未见明显改善(P>0.1)而半暗区组织比重非常明显增加(P<0.001),可见水肿明显减轻。说明光量子疗法增加rCBF,减轻半暗区水肿。     

Kappa-Opioid and NMDA glutamate receptors are differentially targeted within rat medial prefrontal cortex

Activation of kappa-opioid receptors (KOR) in the medial prefrontal cortex (mPFC) modulates excitatory transmission, which may involve interactions with N-methyl-D-aspartate (NMDA) glutamate receptors. We investigated possible anatomical correlates of this modulation by using dual labeling electron microscopy to examine the cellular distributions of antibodies raised against KOR and the R1 subunit of the NMDA receptor (NR1). KOR immunoreactivity primarily was localized to plasma and vesicular membranes of axons and axon terminals that were morphologically heterogeneous. A small proportion of KOR immunoreactivity was associated with cytosolic compartments of dendrites and membranes of glial processes. NR1 labeling was mainly postsynaptic, associated most often with membranes of cytoplasmic organelles in cell bodies and large dendrites and plasmalemmal surfaces of distal dendrites. The remaining NR1-labeled profiles were axonal profiles and glial processes. Of all cellular associations between labeled profiles, the majority were KOR-labeled axons that contacted NR1-immunoreactive dendrites or cell bodies. Occasionally the two antigens were colocalized in axon terminals that formed either asymmetric synapses or displayed varicose morphology. KOR and NR1 also were colocalized within dendrites, and rarely were observed in the same cell bodies. Occasionally glial processes coursing adjacent to axo-spinous appositions expressed both KOR and NR1 immunoreactivity. These results indicate that ligand activation of KOR or NMDA receptors differentially modulates excitatory transmission in the mPFC through pre- and postsynaptic mechanisms, respectively. The data also suggest more minor roles for colocalized KOR and NMDA receptors in shared regulation of presynaptic transmitter release, postsynaptic responsivity, and glial function.     

Effect of drinking on angiotensin-II-induced shifts in regional cerebral blood flow in the rat

A map of brain regions affected by central administration of the octapeptide angiotensin II (AII) and that would further reflect the consequences of AII's well-known dipsogenic action was developed. Regional cerebral blood flow (rCBF) as an indicator of neuronal activity was measured in conscious rats shortly after an ICV bolus injection of 100 ng AII or saline vehicle (VEH). AII-treated animals were further subdivided into two groups that were either permitted to drink [AII (W+)] or whose water was removed when drinking was attempted [AII (W-)]. When compared to VEH condition, blood flow increased significantly within 1 min after AII treatment in 33 of 53 regions sampled in those rats not given an opportunity to drink. In 11 of these 33 regions, ingestion of a small amount of water was associated with a reversal of AII-induced elevation in blood flow [i.e., AII (W+) less than AII (W-)]; these regions included the organum vasculosum lamina terminalis, rostral lateral hypothalamus, supraoptic nuclei, rostral zona incerta, and median eminence. A group of similarly treated rats exhibited a significant elevation of mean arterial blood pressure following AII treatment without significant shifts in arterial blood gases, pH, or bicarbonate. These data are consistent with prominent involvement of the anteroventral third ventricular region of the rat brain. The results further indicate that rCBF may be a sensitive measure for the identification of central sites of action of AII as a dipsogenic agent and may reveal distinctions between regions associated primarily with initiation of drinking and those reflecting the results of subsequent behavioral events.     

Neuroprotective effects of the glutamate release inhibitor 619C89 in temporary middle cerebral artery occlusion

619C89 is a use-dependent Na⁺ channel antagonist that decreases the release of glutamate during ischemia. The efficacy of this drug in reducing infarction volume 72 h after occlusion of the middle cerebral artery (MCA) for 2 h in rats (n = 93) was determined by analysis of TTC-stained coronal section of the brain. Doses of 10, 20, 30 and 50 mg/kg of study drug given i.v. prior to MCA occlusion significantly (P < 0.05−0.01) reduced infarction volume in cortex compared to vehicle controls. Only the 50 mg/kg dose reduced infarction volume in the striatum (P < 0.05). Administration of 50 mg/kg of 619C89 30 and 60 min after the onset of ischemia reduced cortical infarction volume (P < 0.05), but there was no effect when the drug was given 5 min after reperfusion. No post-treatment regimen reduced striatal infarction volume. These results confirm the neuroprotective effects of 619C89 in temporary focal ischemia.     

Endorphinergic mechanisms in cerebral blood flow autoregulation

The influence of naturally occurring opioid peptides (Met-enkephalin (Met-Enk), dynorphin (DYN), β-endorphin (β-EP)) as well as morphine and the opiate antagonist naloxone and specific antisera on cerebral blood flow autoregulation was studied in anesthetized, artificially ventillated rats. Local hypothalamic blood flow (CBF, H₂-gas clearance technique) and total cerebral blood volume (CBV, photoelectric method) were simultaneously recorded. Autoregulation was tested by determining CBF and CBV during consecutive stepwise lowering of the systemic mean arterial pressure to 80, 60 and 40 mm Hg, by hemorrhage. Resting CBF decreased following Met-Enk, DYN, β-EP or morphine administration without simultaneous changes in CBV. Naloxone administration, on the contrary, increased CBV without affecting local CBF. Autoregulation of cerebral blood flow was maintained until 80 mm Hg, but not completely at 60 and 40 mm Hg arterial pressure in the control group. General opiate receptor blockade by 1 mg/kg s.c. naloxone abolished autoregulation at all levels, since CBF and CBV passively followed the arterial pressure changes. Intracerebroventricularly injected naloxone (1 μg/kg) as well as a specific antiserum against β-EP, but not against Met-Enk or DYN, resulted in the very same effect as peripherally injected naloxone. The present findings suggest that central, periventricular β-endorphinergic mechanisms might play a major role in CBF autoregulation.     

Effect of nitro- -arginine on cerebral blood flow and monoamine metabolism during ischemia/reperfusion in the mongolian gerbil

Inhibition of nitric oxide synthase with nitro- -arginine (i.p., 40 mg/kg body weight) in contrast to -arginine (300 mg/kg body weight) delayed the initial recovery of cerebral blood flow (CBF) and altered dopamine (DA) metabolism in brain ischemia/reperfusion of Mongolian gerbils. Similar changes but more severe were observed with pargyline (monoamine oxidase inhibitor). Data suggest nitric oxide involvement in postischemic CBF recovery and modulation of DA metabolism due to nitro- -arginine-induced CBF reduction.     

Local blood flow and glucose consumption in the rat brain during sustained bicuculline-induced seizures

The present study addresses the problem of whether brain structures which have been shown to develop neuronal cell damage in recurrent or prolonged epileptic seizures have higher metabolic rates and/or less pronounced increases in blood flow rates than others during sustained seizures. To that end, local cerebral blood flow (CBF) and glucose utilization (CMRgl) were measured autoradiographically in ventilated rats, in which seizures of 20, 60, or 120 min duration were induced by i.v. bicuculline.
After 20 and 60 min of seizure activity, local CBF increased 2- to 4-fold in most of the 21 structures analysed. However, there was a marked heterogeneity with CBF values varying between 150% (caudoputamen) and 500% (globus pallidus) of control. After 120 min, CBF in several structures, notably cortical and limbic regions, fell in spite of unchanged blood pressure and continued seizure activity.
Changes in local CMR_gl were equally heterogenous, and correlated poorly with blood flow rates. Some structures (the cerebral cortices and 3 limbic areas) showed a sustained 2-4 fold increase in CMR_gl. In these, metabolic rate and blood flow wereinititially matched but CBF subsequently fell to yield a pattern of relative hypoperfusion. Other structures showed no, or only modrate, increases in CMR_gl. In spite of this, CBF increased markedly to yield a pattern of relative hyperemia. It is concluded that bicucullineinduced seizures represent a condition in which structures, observed to be prone to develop cell damage, show grossly enhanced metabolic rate and develop relative underperfusion. Furthermore, the results suggest that structures with a large increase of the metabolic rate during seizures, develop a striking mismatch between local metabolic rate and blood flow.     

Caffeine-induced cerebral blood flow changes in schizophrenia

Summary Cerebral blood flow (CBF) measurements and mental status examinations were performed before and 30 min after oral administration of 250 mg of caffeine or a placebo given under double-blind conditions, in two groups of patients with schizophrenia. Caffeine produced significant CBF reductions but no changes in the patient's clinical condition.     

Activation of 5-HT1C/2 receptors depresses polysynaptic reflexes and excitatory amino acid-induced motoneuron responses in frog spinal cord

Sucrose gap recordings from the ventral roots of isolated, hemisected frog spinal cords were used to evaluate the effects of high concentrations of serotonin (5-HT) and alpha-methyl-5-HT (alpha-Me-5-HT) on the changes in motoneuron potential produced by dorsal root stimulation and by excitatory amino acids and agonists. Bath application of 5-HT in concentrations of 10 microM or greater produced a concentration-dependent motoneuron depolarization. Polysynaptic ventral root potentials evoked by dorsal root stimuli were reduced in both amplitude and area by 5-HT or alpha-Me-5-HT (both 100 microM). This may result from a reduction of the postsynaptic sensitivity of motoneurons to excitatory amino acid transmitters because 5-HT significantly depressed motoneuron depolarizations produced by addition of L-glutamate and L-aspartate to the superfusate. Similarly, 5-HT reduced depolarizations produced by the excitatory amino acid agonists N-methyl-D-aspartate (NMDA), quisqualate, alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA), and kainate. alpha-Me-5-HT reduced NMDA depolarizations. Tetrodotoxin (TTX) did not affect the ability of 5-HT to attenuate NMDA or kainate depolarizations, but did eliminate the 5-HT-induced attenuation of quisqualate and AMPA depolarizations. The glycine receptor site associated with the NMDA receptor did not appear to be affected by 5-HT because saturation of the site by excess glycine did not alter the 5-HT-induced depression of NMDA responses. The 5-HT1C/2 antagonist ketanserin and the 5-HT1A/2 antagonist spiperone significantly attenuated the 5-HT-induced depression of NMDA-depolarizations.(ABSTRACT TRUNCATED AT 250 WORDS)