Blood Flow In Caudate Nucleus Research Articles

Caudate blood flow and volume are reduced in HIV + neurocognitively impaired patients

To evaluate the effects of HIV-associated neurocognitive impairment on caudate blood flow and volume. The authors performed continuous arterial spin labeled MRI on 42 HIV+ patients (23 subsyndromic and 19 HIV neurosymptomatic) on highly active antiretroviral therapy and 17 seronegative controls. They compared caudate blood flow and volume among groups. A stepwise decrease in both caudate blood flow and volume was observed with increasing HIV-associated neurocognitive impairment. Compared with seronegative controls, baseline caudate blood flow was reduced in HIV+ neurosymptomatic patients (p = 0.001) with a similar decreasing trend for subsyndromic HIV+ patients (p = 0.070). Differences in caudate volume were observed only for neurosymptomatic HIV+ patients compared with controls (p = 0.010). A Jonckheere-Terpstra test for trends was significant for both caudate blood flow and volume for each of the three subgroups. Pearson product moment correlation coefficients were not significant between caudate blood flow and volume for each group. Decreasing trends in caudate blood flow and volume were associated with significantly increasing HIV-associated neurocognitive impairment (HNCI), with the greatest decreases observed for more severely impaired patients. However, reductions in caudate blood flow and volume were poorly correlated. Changes in residual caudate blood flow may act as a surrogate biomarker for classifying the degree of HNCI.

A case of spinal cord injury-related pain with baseline rCBF brain SPECT imaging and beneficial response to gabapentin

Central pain following spinal cord injury is poorly understood, and is often resistant to conventional pain therapy regimens. We describe an individual with paraplegia who for many years experienced rapidly fluctuating, severe, unilateral pain below the level of his lesion. Prior to the initiation of pharmacological treatment, regional cerebral blood flow (rCBF) was measured during PAIN and NON-PAIN states using single photon emission computed tomography (SPECT). When experiencing pain, the subject had increased anterior cingulate gyrus blood flow, increased thalamic blood flow bilaterally and increased somatosensory cortex blood flow contralaterally but decreased caudate blood flow bilaterally. The subject's subsequent clinical course included a trial of gabapentin which produced a substantial reduction in frequency and average intensity of his episodic pain and which has been maintained for almost 2 years. This case demonstrates the correspondence between rCBF and pain associated with spinal cord injury and also suggests the potential utility of gabapentin for treatment of this central pain state.

54. Elevated caudate nucleus blood flow in OCD patients with chronic motor tics

Patientswith obsessivecompulsivedisorder(OCD)with and withouta historyof motortics maybe distinguishedbasedontheirclinicalfeatures andcouldconstitutedifferentsubtypesofOCD(McDougle,1993;Zohar, 1997).The presentstudysoughtto identifydifferencesin the regional cerebrrdbIoodflow(rCBF)in OCDpatientswithandwithoutcbmnictic disorder.Twen~-sevenpatientswith OCD,includingsevenwith associatedsimplechronicmotortic disorder,as definedby the DSM-IVand ICD-10,and sixteenage, sex and handednessmatchedhealthycontrols, were studied at rest usirrga high resolutionsingle photon emission computerizedtomography(SPECT)scan and 99mTc-HMPAOas the tracer.The rCBFof 14regionsof interestwas manuallytracedon each individualscan and quantifiedas a percentageof the mean cerebella uptake.SeverityofOCD,anxietyanddepressivesymptomsandpresence of motortics were assessedby the Y-BOCS,HRS-D,HRS-A,MADRS andYale GlobalTics Severi~ Scale.PatientswithOCDandassociated chronictic disordershowedan increasedrf2BFin rightcaudatenucleus comparedto OCD patientswithouttics (C)CDwith tics= 0.96; OCD withouttics= 0.92;p= O.009).OCDpatientswithchronictics sIso had lower severity of obsessive-compulsivesymptoms(global Y-BOCS score),particularlyin the obsessivesymptomssubscale.Thesefindings showingdifferentclinicalfeaturesandrCBFpatternssupportthe notion that OCDwithconcurrentchronictic disordermayconstitutea specific subtypeof OCD.

Intraventricular endothelin-1 uncouples the blood flow: Metabolism relationship in periventricular structures of the rat brain: Involvement of L-type calcium channels

Endothelin-1 (ET) produces contraction of cerebral resistance vessels in vitro and in situ, but also is neuroactive causing increases in tissue energy metabolism as measured by [ 14C]deoxyglucose autoradiography in the intact rat brain. ET may, therefore, disengage the normally tight linkage between cerebral blood flow and tissue metabolism. Using anatomically rigorous autoradiographic and imaging techniques to measure focal blood flow in anesthetized, ventilated rats, we found that intraventricular injection of 9 pmol of ET reduced rates of perfusion by an average of 29% (compared to a saline-injected condition) in 6 individual periventricular structures bordering the injected lateral ventricle. A significant vasoconstrictor effect (41% decrease in blood flow) also occurred in the ipsilateral choroid plexus after ET injection, despite its increased rate of glucose metabolism. We employed a hydrogen clearance method to monitor rates of blood flow serially within the periventricular margin of the caudate nucleus after intraventricular injection of the dihydropyridine calcium-channel antagonist, nimodipine (72 nmol), or 9 pmol ET, alone and in sequence. Nimodipine increased caudate blood flow (by 47%) and prevented the vasoconstriction produced by ET. The results indicate that ET causes vasoconstrictlon in penventricular brain structures and choroid plexus even in the presence of substantial increases in glucose metabolism. The simultaneous stimulation by intraventricular ET of tissue hypermetabolic and vascular constrictor mechanisms, leading to a net reduction of periventricular blood flow, is mediated, at least in part, by dihydropyridine-sensitive calcium L-channels.

Conjugated superoxide dismutase reduces extent of caudate injury after transient focal ischemia in cats.

We tested the efficacy of preischemic and postischemic systemic treatment with 30,000 units polyethylene glycol-conjugated superoxide dismutase in a reperfusion model of focal cerebral ischemia. Forty-one anesthetized cats underwent 2 hours' occlusion of the left middle cerebral artery and both common carotid arteries followed by 4 hours of reperfusion. Cats were blindly assigned to one of three groups: treatment with vehicle (10% polyethylene glycol in saline, n = 17), pretreatment with drug 3 hours before ischemia (n = 12), and posttreatment with drug at the time of reperfusion (n = 12). Size of the ischemic injury was calculated from 2,3,5-triphenyltetrazolium chloride staining. Injury in the caudate nucleus was significantly reduced with pretreatment (28 +/- 6% of ipsilateral caudate volume, mean +/- SEM) compared with the vehicle (56 +/- 8%). Posttreatment did not significantly ameliorate caudate injury (46 +/- 10%). Between the first and second hours of ischemia ipsilateral caudate blood flow determined using microspheres increased significantly from 11 +/- 4 to 16 +/- 5 ml/min/100 g with pretreatment, but blood flow remained constant throughout ischemia with vehicle (8 +/- 2 ml/min/100 g) and posttreatment (10 +/- 3 ml/min/100 g). The size of cortical injury (vehicle, 17 +/- 5%; pretreatment, 11 +/- 3%; posttreatment, 17 +/- 5% of hemispheric volume) did not differ significantly among groups. Somatosensory evoked potential recovery did not differ among groups. We conclude that pretreatment with conjugated superoxide dismutase can ameliorate the extent of injury in an end-artery region, such as the caudate nucleus, in a reperfusion model of focal ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Sympathetic regulation of cerebral blood flow during seizures in newborn lambs

We examined cerebral blood flow (CBF) regulation by the sympathetic nerves in 12 newborn lambs (3-11 days old) during seizures, a potent reflex stimulator of the sympathetic nervous system. CBF was measured with microspheres, and seizures were induced with bicuculline. In six of these lambs, one hemibrain was denervated (D) chronically by interrupting the ipsilateral cervical sympathetic trunk; the other hemibrain remained innervated (I). Before and after 10, 35, and 70 min of seizures, cerebral gray matter blood flow (mean +/- SE ml.min-1.100 g-1) was, respectively, 12 +/- 3 (9%), 71 +/- 12 (21%), 120 +/- 15 (38%), and 54 +/- 5 (14%) greater (P less than 0.05) in the D than in the I hemibrain. In the cerebral white matter, hippocampus, caudate, and thalamus blood flows to the D and I hemibrains were similar before seizures but during seizures they were 10-39% greater (P less than 0.05) in the D than in the I hemibrain. Midbrain, brainstem, and cerebellum D and I blood flows were always similar. In the other six lambs, acute denervation during seizures increased ipsilateral cerebral gray and hippocampus blood flow by 10-31%, but unilateral electrical stimulation decreased ipsilateral cerebral gray, cerebral white, hippocampus, thalamus, and caudate blood flow by 17-27%. The data demonstrate that, during seizures, sympathetic nerve activity modifies regional CBF and the effect is sustained, suggesting a role for the sympathetic nervous system in newborn CBF regulation.

Dynamic cerebral and systemic circulatory effects of adenosine, theophylline and dipyridamole

The effects of intravenous adenosine, dipyridamole and theophylline on local cerebral blood flow were studied in conscious rabbits. Long-term quantitative blood flow measurements were performed in 5 cerebral structures together with tissue pO 2 and pCO 2 measurements by a mass spectrometry technique. In an additional study, the time course of the cerebrovascular changes was determined by thermal clearance. It was found that: firstly, adenosine failed to modify local blood flow except in the caudate nucleus; secondly, dipyridamole increased cerebral blood flow in all 5 structures under study; and lastly, theophylline decreased cerebral blood flow in the same 5 structures. The increase in caudate blood flow induced by adenosine was instantaneous and lasted only for the duration of the infusion, whereas the cerebrovascular changes induced by dipyridamole and theophylline were gradual and persisted after their administration. Theophylline blocked the systemic and cerebrovascular changes caused by adenosine alone and by dipyridamole alone. In anesthetized rabbits, the intracarotid infusion of adenosine showed that the caudate reaction only occurred in the ipsilateral hemisphere. Taken together, our findings suggest that the transport system for adenosine in cerebral vessels is not only species-dependent but also structure-dependent. Furthermore, perivascular adenosine helps to maintain resting cerebrovascular tone and finally, cerebral adenosine may be involved in the control of cerebral blood flow via specific adenosine receptors.

Attenuation of progressive brain hypoperfusion following experimental subarachnoid hemorrhage by large intravenous doses of methylprednisolone

Experimental subarachnoid hemorrhage was produced in chloralose-anesthetized cats by slow injection of 0.5 ml/kg autologous arterial blood into the cisterna magna. As a result, there was an initial (within 5 min) 25.1% decrease in caudate nuclear blood flow as measured by hydrogen clearance. Between 5 min and 3 h postinjection, there was a further and progressive 25.9% decline in caudate blood flow. The hemorrhage also caused a slow increase in intracranial pressure, a decrease in cerebral perfusion pressure, and an increase in caudate vascular resistance. In contrast, the administration of a single 30 mg/kg i.v. dose of methylprednisolone sodium succinate 30 min after the acute hemorrhage resulted in stabilization of caudate blood flow and vascular resistance and some restoration of those parameters toward prehemorrhage values. This effect was not correlated with a decrease in intracranial pressure or an increase in cerebral perfusion pressure. A 15 mg/kg i.v. dose of the drug had only a slight effect on caudate blood flow. A 60 mg/kg i.v. dose, while initially supportive, lost its effect during the later stages of the experiment, indicating a sharp biphasic dose-response relationship for the effect of methylprednisolone on caudate blood flow after subarachnoid hemorrhage. However, of the three doses, only 60 mg/kg significantly decreased the slow posthemorrhage rise in intracranial pressure. The beneficial effect of the 30 mg/kg i.v. dose of the drug on caudate blood flow, separate from an effect on the slow rise in intracranial pressure, suggests that the steroid support of caudate perfusion is due to a direct protective effect of the drug on the microvasculature. Based on previous studies showing an identical dose-response pattern for the ability of methylprednisolone to prevent posttraumatic lipid peroxidation of central nervous system tissue and progressive ischemia development, the possibility of the drug's inhibition of hemorrhage-initiated vasoconstrictor prostanoid action and microvascular lipid peroxidation is proposed.

Influence of chemoreceptors on neurohypophyseal blood flow during hypoxic hypoxia.

Neurohypophyseal blood flow was studied using radiolabelled microspheres in 13 dogs. Hypoxic hypoxia and carbon monoxide hypoxia with similar arterial oxygen contents (CaO2, approximately 8 vol %) were produced. Under conditions of hypoxic hypoxia, 100-200% increases in blood flow in caudate nucleus, white matter, neurohypophysis, and all other brain regions occurred. Similar blood flow responses were observed with carbon monoxide hypoxia in all brain regions except the neurohypophysis. The role of carotid and aortic chemoreceptors in mediating this blood flow response was studied in 6 additional dogs. Similar degrees of hypoxic hypoxia were produced in chemoreceptor-intact and completely denervated animals (CaO2 approximately 8 vol %, PaO2 approximately 33 mm Hg). Hypoxic hypoxia produced a 250% increase in neurohypophyseal blood flow and a concurrent rise in plasma arginine vasopressin from 8 +/- 3 to 52 +/- 8 pg/ml. Chemoreceptor denervation completely inhibited the increase in neurohypophyseal blood flow associated with hypoxic hypoxia. Arginine vasopressin was not increased by hypoxic hypoxia under conditions of complete denervation. A unique role for peripheral chemoreceptors in regulating neurohypophyseal blood flow is postulated.

Systemically administered adenosine increases caudate blood flow in rabbits

Adenosine has been proposed to be a chemical link between cerebral metabolism and blood flow. In the present study, we investigated whether the intravenous or intracarotid administration of adenosine could influence regional cerebral blood flow in anesthetized rabbits. The study was performed with the [ 14C]ethanol tissue sampling technique which enables quantitative, instantaneous, multiregional blood flow measurements. With either mode of adenosine administration, no change in cerebral blood flow was observed, except in the caudate nucleus in which a significant vasodilation took place. These data indicate that, in rabbits exogenous adenosine increases blood flow in highly specific brain areas, by mechanisms that are discussed.

Effect of naloxone on cerebral perfusion and cardiac performance during experimental cerebral ischemia.

Transient global cerebral ischemia (TGI) was induced in awake rats using the "four-vessel" occlusion model of Pulsinelli and Brierley. Blood pressure, arterial blood gases, cerebral blood flow, and cardiac output were measured during the acute (up to 2 hours) and chronic (2 to 72 hours) postischemic time periods. Coincident with the onset of TGI, cardiac output and caudate blood flow were depressed. The former returned to baseline within 30 minutes after the conclusion of TGI, and the latter progressed to hyperemia at 12 hours (81.8 +/- 4.9 vs 68.6 +/- 3.9 ml/min/100 gm tissue (mean +/- standard error of the mean] and oligemia at 72 hours (45.5 +/- 4.8 ml/min/100 gm tissue) post-TGI in the untreated control rats. Arterial blood gases and blood pressure were unchanged. Naloxone (1mg/kg) given at the time of TGI or as late as 60 minutes post-TGI and every 2 hours thereafter for 24 hours or bilateral cervical vagotomy prevented the depression in cardiac output and blocked the hyperemic-oligemic cerebral blood flow pattern that was predictive of stroke in this rat model. Changes in cardiac output after TGI in this model appear to be mediated by parasympathetic pathways to the heart from the brain stem. Opiate receptor blockade probably blocks endogenous opioid peptide stimulation of these brain-stem circulatory centers, which results in inhibition of parasympathetic activity and improvement in cardiac output. The usefulness of naloxone in the treatment of experimental stroke may be a function of its ability to improve cerebral perfusion in pressure-passive cerebrovascular territories. Variations in cardiac output during experimental stroke may explain the dissimilar responses to naloxone treatment reported by other investigators of experimental stroke.

O4C1300) - Nigral-induced decrease in blood flow in caudate nucleus and its modification by some drugs.

O4C1300) - Nigral-induced decrease in blood flow in caudate nucleus and its modification by some drugs.

Changes in brain blood flow associated with deltamethrin-induced choreoathetosis in the rat

Deltamethrin is a pyrethroid insecticide which produces reversible motor symptoms in mammals involving facial movements, progressive incoordination, and choreoathetosis. These symptoms were found to be preceded and accompanied by increases in blood flow in the caudate nucleus and cerebral cortex of conscious rats. Blood flow, measured by the hydrogen polarography method, showed a 2.8-3.8 fold increase in the caudate nucleus and a 1.9-2.6 increase in the cortex after intraperitoneal deltamethrin. The increase in caudate blood flow provided an early and sensitive indicator of the development of motor symptoms, and preceded development of EEG spike discharges. A different pattern of motor symptoms consisting largely of tremor with no choreoathetosis was produced for comparison using another pyrethroid, cismethrin. This, whilst producing a similar increase in cortical flow, did not produce the disproportionate increase in caudate flow characteristic of deltamethrin. Although the actions of deltamethrin were shown not to be restricted to the extrapyramidal system, the selectivity of the blood flow increases, and the nature of the symptoms produced show deltamethrin to be a useful tool for the production of experimental extrapyramidal motor hyperactivity.

Correlation of local blood flow, glucose consumption and probability of necrosis following a middle cerebral artery occlusion in the cat.

At defined coronal sections, the surface area of infarcted tissue was measured 4 days after the occlusion of the middle artery in 11 cats. In groups of cats treated with ifenprodil (5.6 and 16.7 microgram/kg . min over 3 h. 5 min after the occlusion), the infarcted surface was significantly decreased. The topographic localization of the infarction was studied in control and treated cats. This established necrosis was correlated with measures of focal cerebral blood flow and glucose consumption 3.5 h after the middle cerebral artery occlusion. Grey matter blood flow was universally low in untreated cats, but in cats treated with ifenprodil (5.6 microgram/kg . min) cortical and caudate nucleus blood flow was 2-3 times greater, even in those regions that were later infarcted in the treated cats. Glucose consumption was similarly reduced in untreated cats but there was little difference between the control and drug-treated cats except in some areas where drug treatment appeared to further reduce the values for focal glucose consumption. These regions correlated with those in which infarction was later found in the cats treated with ifenprodil. It is hoped that such correlations between pathology. flow and metabolism could help the search for effective pharmacotherapy of cerebrovascular disease.

Parasympathomimetic influence of carbachol on local cerebral blood flow in the rabbit by a direct vasodilator action and an inhibition of the sympathetic-mediated vasoconstriction.

1 Two sorts of effect of carbachol on local cerebral blood flow (caudate nucleus) have been studied: (a) a direct action on the arterial smooth muscle; (b) an interaction with the adrenergic (sympathetic) constrictor system which innervates the vascular system of this nucleus. 2 Continuous measurements of the following variables were performed in lightly anaesthetized rabbits: local blood flow (caudate nucleus), arterial blood pressure, PaO2, PaCO2. 3 After blockade of the nicotinic synapses in the superior cervical sympathetic ganglion by local hexamethonium injection, carbachol was infused into the common carotid artery, thus minimizing systemic effects of this drug. Infusions of 0.6, 1.3 and 2.5 micrograms kg-1 min-1 induced mean increases in caudate blood flow of about 8, 17 and 37% respectively, without notable modifications of other variables measured. 4 The dilator effect of 2.5 micrograms kg-1 min-1 carbachol was reduced to a mean of 12% after intravenous injection of 0.5 mg/kg atropine, and could be totally abolished by higher doses (1 to 1.5 mg/kg). 5 Administration of 2.5 micrograms kg-1 min-1 of carbachol diminished by more than 50% the reduction in caudate blood flow induced by postganglionic stimulation of the cervical sympathetic chain, but did not affect the reduction of flow obtained by intravenous infusion of noradrenaline (2.5 to 5.0 micrograms kg-1 min-1). This inhibition of the adrenergic (sympathetic) system by carbachol was not modified by high doses of atropine (1 mg/kg i.v.). 6 We conclude that: (a) the local cerebral blood flow of a deep structure can be significantly modified by activation of vascular muscarinic receptors; (b) activation of non-muscarinic prejunctional cholinoceptors can cause inhibition of the sympathetic fibres innervating the vascular bed of the same structure.

The effect of alpha-adrenergic innervation on caudate blood flow.

A thermal diffusion probe, with cannulas for intracerebral microinfusion of drugs and an electrode to monitor electroencephalographic (EEG) activity, was used to examine the local effect of vasoactive amines in a 4 to 5 mm sphere of caudate nucleus in cats. The results demonstrated that it is possible to alter local cerebral blood flow (CBF) without causing any change in systemic blood pressure or heart rate, or in CBF and the EEG in the opposite caudate. One-microliter intracerebral injections, containing varying amounts of phenylephrine, increased local CBF in proportion to dose. The effect was blocked by intracerebral infusion of phentolamine. However, local alpha-adrenergic blockade did not inhibit vascular responses to blood pressure elevation or to metabolic influences on local blood flow.

The cholinergic pathway to cerebral blood vessels. II. Physiological studies.

The effect of stimulating the greater superficial petrosal nerve (g.s.p.n.) upon retroglenoid venous blood flow has been tested in anaesthetized, paralysed and artificially ventilated rats. In 11 out of 15 tests, blood flow increased by an average of 25% with a time to peak response of 28 s. This response was abolished with the injection of atropine 0.1 mg kg-1 injected intra-arterially. With both petrosal nerves intact, the administration of 6-7% CO2 in air or 15% O2 in N2 caused average increases in blood flow of 105% and 45% respectively. These responses were not affected by bilateral section of the g.s.p.n. Similar experiments were carried out in 5 anaesthetized, spontaneously breathing rabbits in which, in addition to PaCO2 and PaO2, PO2, PCO2 and blood flow in the caudate nucleus were measured continuously using chronically implanted mass spectrometer catheters and heated thermistors. Caudate nucleus blood flow increased in response to hypoxia and hypercapnia and this response was not significantly affected by section of one or both g.s.p.n., sinus or vagus nerves. With section of sinus and vagus nerves, blood flow changed passively with arterial pressure.

The cholinergic pathway to cerebral blood vessels. I. Morphological studies.

The application of cobalt chloride to the peripheral cut end of the greater superficial petrosal nerve (g.s.p.n.) in rats revealed that only a few fibers in the plexus of nerves on the adventitial surface of the internal carotid artery were in axonal continuity with the g.s.p.n. A similarly small contribution of cholinergic fibers to cerebral blood vessels from this nerve was suggested by the observation that section of the g.s.p.n. resulted in an insignificant reduction in the density of the AChE-staining plexus in the internal carotid and cerebral arteries and in the incidence of at most 2% degenerate terminals of those observed on the middle cerebral artery. Alternative explanations of the results are discussed: that the AChE-staining fibers are postganglionic, that the time course for degeneration is unusually slow and that non-cholinergic fibers stain non-specifically for AChE. It is concluded that a cholinergic dilator pathway is most probably carried by the g.s.p.n. but that it is not unique.

Decrease in neostriatal blood flow after d-amphetamine administration or electrical stimulation of the substantia nigra

Local blood flow was measured in the caudate nuclei and, in some cases, other areas of rat and monkey brain by the hydrogen clearance technique. Resting values for caudate blood flow in the rat were similar to those reported elsewhere, i.e. 69 ± 4 ml/min/100 g in the caudate. Administering d-amphetamine sulfate (0.5 mg/kg, i.p.) to rats reduced caudate flow by a maximum of about 33% after 30 min; this effect could be blocked by pretreatment with haloperidol (5.0 mg/kg, i.p.), a drug that blocks dopamine receptors. d-Amphetamine sulfate (1.5 mg/kg) also reduced caudate but not cortical blood flow in unanesthetized monkeys. Electrical stimulation of the pars compacta of the substantia nigra reduced ipsilateral caudate flow by about 25% without affecting flow in the contralateral caudate. This effect varied with the frequency and intensity of stimulation. These studies suggest that the intraparenchymal release of brain dopamine may modify intraparenchymal (local) blood flow.

Pharmacological evidence in vitro and in vivo for functional beta1 receptors in the cerebral circulation

Blood flow in the caudate nucleus was measured by the thermoclearance technique in non-anesthetized rabbits, accompanied by recording of electrocorticogram, systemic blood pressure, and Pao2 and Paco2 (mass spectrometry). Isoprenaline increased caudate nucleus blood flow and reduced systemic blood pressure. The beta2-receptor agonist, terbutaline, on the other hand, had only peripheral effects. The caudate nucleus flow response was selectively blocked by the beta1-receptor antagonist, practolol, whereas propranolol inhibited all effects of both agonists. Isoprenaline dilated isolated pieces of the tributary artery (middle cerebral) tested in cats, the effect being inhibited not only by propranolol but also by practolol. The results offer further evidence for the view that the beta-receptors in the cerebral vascular bed are of the beta1-type.