Extracerebral Vessels Research Articles

Increased visinin-like protein-1, YKL-40, lipocalin-2, and IL-23 levels in patients with migraine

ABSTRACT Background Migraine is a type of primary headache caused by changes in the trigeminal system and has been reported to be associated with neurovascular inflammation of cerebral and extracerebral vessels. Objective It is known that inflammation is an important process in the pathogenesis of migraine. It has been shown that the molecules of visinin-like protein 1 (Vilip-1), YKL-40, lipocalin-2 and interleukin (IL)-23 play a role in the inflammatory process. Our aim is to investigate the role of this molecule in the metabolic pathway of migraine disease. Methods Fifty migraine patients with and without aura in the interictal period were included in the study. Vilip-1, YKL-40, lipocalin-2, and IL-23 levels were measured by ELISA method. Results Serum vilip-1, YKL-40, lipocalin-2, and IL-23 levels were found to be significantly higher in migraine patients compared to the control group. We found that this molecule increased significantly in migraine subgroups compared to the control group (p < 0.001). A positive significant correlation was found between vilip-1 level and YKL-40 and lipocalin-2 levels in migraine patients. In addition, a positive correlation was observed between visual analogue scale score, number of days with pain and vilip-1 level (p < 0.01). The results of our study showed that activation of inflammatory mediators may play a role in the pathogenesis of migraine disease. In addition, our study is valuable in that inflammatory molecules are high in the interictal period and these biomarkers have never been analyzed in migraine patients. However, we still believe that larger studies are needed to explain the role of vilip-1, YKL-40, lipocalin-2, and IL-23 in the molecular mechanism of migraine disease.

The study of serum C-reactive protein, Serum cystatin C, and carbohydrate antigen 125 in patients with acute ischemic stroke.

Stroke is the most common, deadly, and complicating neurological disease. Many studies have shown that the levels of some acute inflammatory reactants in people with ischemic stroke are higher than average. Therefore, in this study, three acute inflammatory reactants, i.e., C-reactive protein, Serum cystatin C, and carbohydrate antigen 125, were evaluated in patients with acute ischemic stroke to consider the association between these serums with intra and extra-cerebral vessels stenosis. In this cross-sectional study, 90 patients with non-embolic ischemic stroke were evaluated. The diagnosis was by physical examination, rejection of emboli, and brain imaging. Blood samples were taken in the first 24 hours of a stroke. ELISA test was used to measure CRP, Serum cystatin C, and CA125. Doppler ultrasound of cerebral arteries was also performed in the first five days. Independent chi-square and t-tests were used to analyze the data. The result of CRP level in patients with stenosis was 7.58±1.33μg/ml and in patients without stenosis was 4.10±1.75μg/ml (p = 0.004). Also, there was a significant relationship between serum CRP level and stenosis (p = 0.003). In patients with abnormal CRP, the internal carotid artery, middle cerebral artery, and anterior cerebral artery were the most involved. In patients with normal CRP, the most involved arteries were the anterior cerebral artery, internal carotid artery, and middle cerebral artery, respectively. There was a significant relationship between serum CRP level and the location of internal carotid artery stenosis (p = 0.015) and middle cerebral artery (p = 0.006). The amount of cystatin C between the normal CRP and abnormal CRP groups was statistically significant so that its concentration in the normal group was less than in the abnormal group (p = 0.04). The results of measuring the serum concentration of carbohydrate antigen 125 showed that the serum level in the normal group was statistically lower than in the abnormal group (P = 0.02). The results showed that stenosis of the internal carotid artery and middle cerebral artery is more common in patients with ischemic stroke with high serum CRP levels. This finding suggests that abnormal CRP may be more associated with narrowing some cerebral arteries.

Predictive value of laboratory parameters in childhood migraine.

Migraine is a neurovascular disease characterized by inflammation of the cerebral and extra cerebral vessels and appears in the form of attacks. Although the pathophysiology of migraine is not fully known, the data obtained because of long-term studies reliably support the presence of a potential relationship between migraine pathogenesis and platelet biology. The aim of this study was to investigate the effect of migraine on MPV and other blood parameters as well as the relationship between the hematologic parameters and characteristics of the headache and whether they possess diagnostic value as inflammation and platelet biology play a fundamental role in the disorder. The study group consisted of 56 patients who were followed up and treated with a diagnosis of migraine and 45 healthy patients. The median creatinine, CRP and TSH values of the children in the migraine group were found to be statistically significantly higher than the healthy control group. Serum iron levels of the migraine group were found to be statistically significantly lower than the control group. No statistically significant difference was found between the two groups in terms of MPV. However, when we examined only the patient group, we found MPV to be statistically significantly higher in girls. Increased MPV and decreased serum iron levels may be related to migraine. More comprehensive studies including a larger population are required to evaluate the specific parameters that may guide the follow-up and treatment of the disorder with simple tests to be used in routine practice and to elucidate the underlying pathophysiology.

Four-dimensional MRI flow examinations in cerebral and extracerebral vessels - ready for clinical routine?

To evaluate the feasibility of 4-dimensional (4D) flow MRI for the clinical assessment of cerebral and extracerebral vascular hemodynamics in patients with neurovascular disease. 4D flow MRI has been applied in multiple studies to qualitatively and quantitatively study intracranial aneurysm blood flow for potential risk stratification and to assess treatment efficacy of various neurovascular lesions, including intraaneurysmal and parent artery blood flow after flow diverter stent placement and staged embolizations of arteriovenous malformations and vein of Galen aneurysmal malformations. Recently, the technique has been utilized to characterize age-related changes of normal cerebral hemodynamics in healthy individuals over a broad age range. 4D flow MRI is a useful tool for the noninvasive, volumetric and quantitative hemodynamic assessment of neurovascular disease without the need for gadolinium contrast agents. Further improvements are warranted to overcome technical limitations before broader clinical implementation. Current developments, such as advanced acceleration techniques (parallel imaging and compressed sensing) for faster data acquisition, dual or multiple velocity encoding strategies for more accurate arterial and venous flow quantification, ultrahigh-field strengths to achieve higher spatial resolution and streamlined postprocessing workflow for more efficient and standardized flow analysis, are promising advancements in 4D flow MRI.

Low fetuin-A level in migraine: a case–control study

Migraine is a type of primary headache which is caused by the alterations in trigeminovascular system. Migraine attacks are associated with neurovascular inflammation of the cerebral and extracerebral vessels, but its pathophysiological mechanisms have not still been fully delineated. Also, migraine has been found to be associated with higher risks for various metabolic disorders. Thus, we aimed to investigate the matrix metalloproteinases (MMP), fetuin-A, ghrelin, and omentin levels which have important roles in metabolic disorders and inflammation, and to examine their relationship with migraine subtypes and attack frequency. Forty-nine migraine patients and 30 age- and sex-matched healthy control subjects were enrolled. Migraine diagnosis was confirmed according to the International Classification of Headache Disorders-II diagnostic criteria. Analyses of MMP9,MMP3, ghrelin, omentin, and fetuin-A were performed by the ELISA method. Fetuin-A, MMP-9, and MMP-3 levels were significantly lower in migraine than controls (p < 0.05). There were no significant differences between groups with respect to omentin and ghrelin (p > 0.05). In migraine patients, serum fetuin-A levels were positively correlated with MMP-9 and negatively correlated with MMP-3. MMP-3, MMP-9, fetuin-A, omentin and ghrelin levels did not correlate with age, disease duration, or frequency of migraine headache (p > 0.05). Migraine patients have lower fetuin-A, MMP-3 and MMP-9 levels than healthy individuals. Migraine patients have low fetuin-A levels, which may be related to the pathogenesis of migraine. The importance and impact of our findings on the pathogenesis, characteristics, and treatment of migraine needs to be investigated in further detailed studies.

High salt intake abolishes AT2-mediated vasodilation of pial arterioles in rats

Angiotensin II (Ang II) induces constriction (AT(1)) and dilation (AT(2) receptors) of cerebral arterioles. High sodium intake induces changes in receptors expression and loss of AT(2)-mediated vasodilation in extracerebral vessels. We investigated whether high salt modifies the AT(2)-mediated response of cerebral arterioles. Three-month-old male Wistar rats received drinking water supplemented or not with 1% NaCl. We measured at day 4 or 30 plasma aldosterone concentration, AT receptors expression (brain microvessels, western blot, RT-qPCR), internal diameter of pial arterioles (cranial window) following suffusion with Ang II (10(-6) mol/l, or 10(-8) mol/l + losartan 10(-5) mol/l), serotonin (5-HT, 10(-6) mol/l), sodium nitroprusside (10(-5) mol/l) and adenosine diphosphate (ADP, 10(-4) mol/l). High salt did not modify arterial pressure, baseline arteriolar diameter, vasoconstriction to Ang II or 5-HT, nor vasodilation to SNP. High salt lowered plasma aldosterone concentration (d4 138 ± 71 not significant vs. control 338 ± 73; d30 150 ± 21 P < 0.05 vs. control 517 ± 79 μmol/l). AT receptors mRNA did not change while protein level of AT(2) receptors decreased at d4 (64 ± 9% of control, P < 0.05). AT(2)-mediated vasodilation (control d4; d30 8 ± 2; 5 ± 2%) was abolished at d4 (-2 ± 2%, P < 0.05) and reversed to vasoconstriction at d30 (-7 ± 2%, P < 0.05). ADP-induced vasodilation is abolished at d30 (2 ± 2, P < 0.05 vs. control 19 ± 4%). High salt specifically abolishes AT(2)-mediated vasodilation, immediately, via decreased level of AT(2) receptor protein, and after 30 days, in association with abolition of endothelial vasodilation. Such loss of AT(2)-mediated vasodilation may be deleterious in case of stroke.

The PACAP Receptor: A Novel Target for Migraine Treatment

The origin of migraine pain has not yet been clarified, but accumulating data point to neuropeptides present in the perivascular space of cranial vessels as important mediators of nociceptive input during migraine attacks. Pituitary adenylate cyclase-activating polypeptide (PACAP) is present in sensory trigeminal neurons and may modulate nociception at different levels of the nervous system. Human experimental studies have shown that PACAP-38 infusion induces marked dilatation of extracerebral vessels and delayed migraine-like attacks in migraine patients. PACAP selectively activates the PAC(1) receptor, which suggests a possible signaling pathway implicated in migraine pain. This review summarizes the current evidence supporting the involvement of PACAP in migraine pathophysiology and the PAC(1) receptor as a possible novel target for migraine treatment.

Stroke in Sickle Cell Anemia After Excellent Response to Hydroxyurea.

Abstract 4622 IntroductionStrokes occur in about 10% of children with sickle cell anemia (SS) less than 10 years old. These strokes are usually ischemic in nature. Stroke due to SS in adults is less common and is usually hemorrhagic in nature. We wish to report an unusual adult patient with SS and excellent response to HU who developed a stroke that was unrelated to SS. Case Report and ResultsA 35-year-old female with sickle cell anemia had mitral valve prolapse and migraine headaches presented 2 days after developing abrupt bilateral blurry vision, left facial numbness and weakness of her left leg. Her SS has been complicated by acute chest syndrome, bilateral hip avascular necrosis and frequent painful crises prior to hydroxyurea (HU) therapy. She was enrolled in the multicenter study of hydroxyurea (MSH) in SS and has been on 2500mg of HU per day for the past 13 years. She had an excellent response to HU with no recurrent acute chest syndrome and decreased need for blood transfusion. After starting HU, the frequency of crises requiring hospital admission decreased from 1 admission every 1 to 2 months to less than 1 admission per year except when hydroxyurea was discontinued for pregnancy. Her fetal hemoglobin increased from 6.1 % before HU to a maximum of 45%. Her MCV increased from 96 fl to a maximum of 132 fl and Hb from 8.0 g/dl to 9.8 g/dl Her exam was remarkable for left lower extremity weakness which was more pronounced proximally. All cranial nerves were intact and there was normal sensation bilaterally. CT scan of the brain showed three foci of hypodensity and MRI of the brain showed increased signal on T2, FLAIR and diffusion weighted images within the frontoparietal deep white matter consistent with infarction in the border zone of the middle cerebral artery (MCA)-anterior cerebral artery (ACA). MR angiography of the intracerebral and extracerebral vessels demonstrated focal narrowing of the right MCA at the trifurcation suggesting an embolic cause. Common causes of stroke were ruled out with routine studies. Her hemoglobin electrophoresis after admission but before blood exchange transfusion showed HbS of 55% and HbF of 45%. She underwent exchange transfusion 2 days after admission and was started on chronic blood exchange transfusions with the assumption that she had ischemic stroke due to SS. Initial transthoracic echocardiogram with contrast injection did not show an atrial shunt. Follow-up transesophageal echocardiogram after discharge showed a secundum atrial septal defect with a defect size of 1.4 cm. Right heart catheterization was performed and the pulmonary flow to systemic flow (Qp/Qs) was 1.7:1. An Amplatzer atrial septal defect (ASD) closure device was deployed with transesophageal echocardiographic guidance and a large thrombus was removed from the right atrium. At the patient's request exchange red cell transfusions were discontinued. The patient has continued treatment with hydroxyurea and aspirin. ConclusionsYoung patients with cryptogenic stroke have a much higher prevalence of atrial shunts and in particular patent foramen ovale than patients with other forms of stroke and therefore a cause-effect association is suggested. Young adults with stroke should be evaluated for common and reversible causes of stroke including paroxysmal emboli. Transesophageal echocardiography is the gold standard for diagnosing atrial shunts. Strokes in patients younger than age 55 are related to paroxysmal emboli and have a risk of recurrence of approximately 30% within one year. High risk features for stroke recurrence with an atrial shunt include hypercoagulable states, large opening and presence of an atrial septal aneurysm. Optimal management of patients with a stroke and an atrial shunt is unknown. Options include surgical closure, percutaneous device closure, anticoagulation and antiplatelet therapy. Patients with sickle cell disease and stroke should receive long term blood transfusions to reduce HbS below 30% if the stroke is felt to be related to sickle cell disease vasculopathy. The patient described with SS had a stroke and had an atrial septal defect that was repaired. The MRI/MRA findings are consistent with paroxysmal emboli. The patient is receiving treatment with hydroxyurea and aspirin having discontinued red cell exchange transfusions and at two years of follow-up has not had a recurrent stroke. Disclosures:No relevant conflicts of interest to declare.

On the mechanism of brain injuries. By Alexander Miles, MD, FRCS. Edin. Syme Surgical Fellow (From the Laboratory of the Royal College of Physicians, Edinburgh) Brain 1892: 15; 153 189; Experimental cerebral concussion. By D. Denny Brown and W. Ritchie Russell (From the Laboratory of Physiology, Oxford) Brain 1941: 64; 93 164

That a bang on the head may prove fatal has been known since Biblical times. Despite the celebrated description by Alexis Littre in 1705 of a condemned criminal who anticipated his executioner by head-banging until dead but without breaking his skull, the nature of fracture-less head injury is not so clear. Although many doubt that this can happen, no less an authority than Mr Jonathan Hutchinson has argued that violence of the shake may itself lead to death. Do uncontrolled brain vibrations follow rapid alteration in shape of the skull (as proposed by Professor Miller of Edinburgh)? Perhaps not, since the brain has some freedom of manoeuvre in the cranium: it is a hollow structure, requiring I atmosphere pressure to cause compression by 1/25 000th of its volume; and the meninges or tentorium must tear in the face of such distortions. Is it due to diffuse petechial haemorrhage and cerebral contusions? Could the explanation lie in focal brain lesions caused by squeezing the intracranial vessels or congesting their venous drainage? Is it all due to reflex changes in brain perfusion dependent on cardiac output and peripheral nerve stimulation? Or is it merely a ‘ fons et origo mali ’? To answer these questions, Dr Miles has experimented on anaesthetized rabbits, struck variously on the head with a force insufficient to cause death, and observed the effects. He notices profound irregularities and slowing of the heart beat, and a reduced respiratory rate. The altered reactivity of blood vessels and poor oxygenation, identical to ‘anaemia of the brain’ observed following ligation of the main extracerebral vessels, depend on efferent discharges in the restiform bodies. Studying anaesthetized experimental animals and pigs with swine fever being slaughtered, Dr Miles concludes that this reflex vasospasm leads to tetanus followed by paralysis and cardio-respiratory collapse. Next, …

Cyanonemertes elegans, new genus, new species, a marine hoplonemertean from Washington state, U.S.A

Cyanonemertes elegans, new genus and species, is described as a member of the order Hoplonemertea, suborder Monostilifera. In general morphology, it appears to be most closely related to the genus Amphiporus (family Amphiporidae). The most important features justifying the new taxon are: 1) cephalic muscle layer with anteriorly divided longitudinal musculature, 2) diagonal muscles of non-fasciated, lattice type, 3) retractor muscles derived from the outer portion of the longitudinal musculature, 4) cephalic blood system with extra-cerebral vessels, 5) rhynchocoel extending almost to posterior end of body, 6) rhynchocoel wall bilayered, 7) neurochord cells absent, 8) rhynchodeum with an outer layer of longitudinal muscle, 9) central stylet-basis complex present, and 10) proboscis sheath with thick muscular plate.

Clinical Diagnosis of Vertebrobasilar Insufficiency: Resident's Case Problem

Resident's case problem. Vertigo and visual disturbances are common symptoms associated with vertebrobasilar insufficiency (VBI), but the physical examination procedures to verify the existence of VBI have not been validated in the literature. The objective of this resident's case problem is to demonstrate how a patient's complaint of vertigo and visual disturbances, combined with positive clinical examination findings, can be a potential medical screening tool for VBI. The patient in this report was initially referred to physical therapy for neck pain. However, the patient's chief concerns identified during the history were (1) vertigo, (2) visual disturbances, (3) headache, and (4) right shoulder region pain. Clinical VBI tests were performed, whereby the patient's vertigo and visual disturbances were reproduced with cervical spine extension. The patient was sent back to the referring physician to be evaluated for possible VBI. Diagnostic imaging tests were ordered. Carotid ultrasound revealed 80% to 90% stenosis in the proximal left internal carotid artery, and magnetic resonance angiography of the extracerebral vessels showed greater than 90% stenosis of the left internal carotid artery. VBI may be present in patients with subjective reports of vertigo and visual disturbances that are reproduced with VBI physical examination procedures.

Ascending Arterial Blood Flow Velocities during Cardiac Diastole in Critical Care Patients - A Characteristic Flow Pattern with a Bad Prognosis

Pulsed Doppler ultrasound is a standard noninvasive investigation to measure the velocity and pulsatility of blood flow within the major intracranial and organ-supplying arteries in critical care patients. The normal arterial flow pattern in organ-supplying vessels is characterised by a systolic-diastolic forward flow which is caused by the aortic "Windkessel" function and the low peripheral resistance of the parenchymatous organs. A variety of well known pathological conditions may cause a change of the vascular characteristics within the perfused organs which are diagnosed by the typical changes of the flow pattern in the supplying arteries. In the cardiac diastole, however, there is always a slow decrease of the flow velocity which is terminated by the onset of the following systole. We report on 11 patients investigated by Doppler ultrasound during their stay in our intensive care unit. All these patients presented a markedly different flow pattern measured in their intra- and/or extracerebral vessels. This very distinctive flow pattern is characterised by a diastolic ascent of the arterial flow velocity and is caused by an excessively increased venous pressure within the draining veins of the affected organs. All patients died due to (multiple) organ failure. It is of major importance to be aware of the rare but very characteristic flow pattern described here because of the poor prognosis associated with it.

Rizatriptan does not change cerebral blood flow velocity during migraine attacks

Rizatriptan represents a major advance in the treatment of migraine attack: inhibition of peripheral trigeminal nerve and constriction of intracranial extracerebral blood vessels have been proposed as its main antimigraine mechanisms of action. Although many studies may suggest that rizatriptan causes highly selective vasoconstriction within intracranial extracerebral vessels (i.e., meningeal arteries), no literature data are available to date on possible cerebral hemodynamic changes in humans after treatment with rizatriptan. The aim of this study was to evaluate the effect of rizatriptan on cerebral blood flow velocity performing transcranial Doppler during spontaneous attacks of migraine without aura. Fourteen patients suffering from migraine without aura were monitored to evaluate mean flow velocity changes on both middle cerebral arteries during migraine attack 30 min before and 120 min after oral administration of rizatriptan 10 mg. Monitoring was repeated for 30 min during the pain-free period. All patients turned out to be drug responders and no significant mean flow velocity changes were observed between the pain-free period and pre-treatment phase; besides no significant difference in mean flow velocity value have been detected between the periods after the drug administration during the attack versus both pre-treatment period and pain-free phase. These findings indicate that the antimigraine action of rizatriptan is not associated with clear intracranial cerebral hemodynamic changes and may support its cerebrovascular safety.

Mechanisms of action of the 5-HT1B/1D receptor agonists.

Recent studies of the pathophysiology of migraine provide evidence that the headache phase is associated with multiple physiologic actions. These actions include the release of vasoactive neuropeptides by the trigeminovascular system, vasodilation of intracranial extracerebral vessels, and increased nociceptive neurotransmission within the central trigeminocervical complex. The 5-HT(1B/1D) receptor agonists, collectively known as triptans, are a major advance in the treatment of migraine. The beneficial effects of the triptans in patients with migraine are related to their multiple mechanisms of action at sites implicated in the pathophysiology of migraine. These mechanisms are mediated by 5-HT(1B/1D) receptors and include vasoconstriction of painfully dilated cerebral blood vessels, inhibition of the release of vasoactive neuropeptides by trigeminal nerves, and inhibition of nociceptive neurotransmission. The high affinity of the triptans for 5-HT(1B/1D) receptors and their favorable pharmacologic properties contribute to the beneficial effects of these drugs, including rapid onset of action, effective relief of headache and associated symptoms, and low incidence of adverse effects.

Stimulation of the middle meningeal artery leads to Fos expression in the trigeminocervical nucleus: a comparative study of monkey and cat

The pain of a migraine attack is often described as unilateral, with a throbbing or pulsating quality. The middle meningeal artery (MMA) is the largest artery supplying the dura mater, is paired, and pain-producing in humans. This artery, or its branches, and other large intracranial extracerebral vessels have been implicated in the pathophysiology of migraine by theories suggesting neurogenic inflammation or cranial vasodilatation, or both, as explanations for the pain of migraine. Having previously studied in detail the distribution of the second order neurons that are involved in the transmission of nociceptive signals from intracranial venous sinuses, we sought to compare the distribution of second order neurons from a pain-producing intracranial artery in both monkey and cat. By electrically stimulating the middle meningeal artery in these species and using immunohistochemical detection of the proto-oncogene Fos as a marker of neuronal activation, we have mapped the sites of the central trigeminal neurons which may be involved in transmission of nociception from intracranial extracerebral arteries. Ten cats and 3 monkeys were anaesthetised with α-chloralose and the middle meningeal artery was isolated following a temporal craniotomy. The animals were maintained under stable anaesthesia for 24 h to allow Fos expression due to the initial surgery to dissipate. Following the rest period, the vessel was carefully lifted onto hook electrodes, and then left alone in control animals (cat n = 3), or stimulated (cat n = 6, monkey n = 3). Stimulation of the left middle meningeal artery evoked Fos expression in the trigeminocervical nucleus, consisting of the dorsal horn of the caudal medulla and upper 2 divisions of the cervical spinal cord, on both the ipsilateral and contralateral sides. Cats had larger amounts of Fos expressed on the ipsilateral than on the contralateral side. Fos expression in the caudal nucleus tractus solitarius and its caudal extension in lamina X of the spinal cord was seen bilaterally in response to middle meningeal artery stimulation. This study demonstrates a comparable anatomical distribution of Fos activation between cat and monkey and, when compared with previous studies, between this arterial structure and the superior sagittal sinus. These data add to the overall picture of the trigeminovascular innervation of the intracranial pain-producing vessels showing marked anatomical overlap which is consistent with the often poorly localised pain of migraine.

Blood flow velocity changes in carotid and vertebral arteries with stellate ganglion block: Measurement by magnetic resonance imaging using a direct bolus tracking method

Background and Objectives. Stellate ganglion block (SGB) leads to vasodilation of the head and neck, as a result of a regional sympathetic blockade. However, in such cases, controversy remains concerning changes in cerebral and extracerebral blood flow in the head. We estimated the effect of SGB on blood flow in the head by measuring the blood flow velocity in cervical vessels, using magnetic resonance imaging and the direct bolus tracking method. This noninvasive method is free from potential artifacts of bones and other connective tissues. Methods. Seven adult patients with acute or chronic pain in the head or neck underwent SGBs, using an anterior paratracheal approach with 6–8 mL of 1% mepivacaine (3 right and 4 left SGBs). Blood flow velocity in common carotid and vertebral arteries (CCA and VA) was measured simultaneously before and after SGB, using the direct bolus tracking method. Results. On the side of SGB, blood flow velocity in CCA significantly increased ( P < .002), whereas velocity in VA was unchanged after SGB. On the side contralateral to the SGB, significant changes in blood flow velocity in CCA and VA were never observed. Conclusions. Blood from the VA flows primarily to cerebral vessels, whereas that from CCA goes to both cerebral and extracerebral vessels. Given the presumed differences in blood flow distribution through the VA and CCA, we assume that the observed CCA blood flow increases, ipsilateral to the SGB, primarily as a result of vasodilation of extracerebral vessels and independent of changes in brain blood flow.

Nitrergic innervation of rat brain vasculature.

Nitric oxide synthase has been located in the brain, in several neuronal populations which appear in close contact either with the microvasculature or the external surface of extracerebral vessels. These data provide structural support to the pharmacological evidences of the nitric oxide participation in the regulation of vascular tone of brain blood vessels.

Differences in contrast enhancement between intra- and extra-axial lesions after two hours of iodine injection.

In order to try to improve discrimination between the brain lesions that produce damage to the brain-blood barrier and those which are irrigated by extracerebral vessels, the behavior of contrast enhancement up to two hours after iodine injection was studied in two groups of patients. Eight patients had extra-axial lesions (7 meningiomas, one acoustic neuroma) and eleven had intra-axial lesions (6 of astrocytic type, 3 metastases, 2 inflammatory). In the first group, mean values of the lesioned areas in HU decreased progressively with time. However, in many cases in the second group the values at the end of the study were equal to or higher than those observed immediately after contrast medium injection. Highly significant differences were observed between the two groups. The contrast medium in the intra-axial lesions conform to the behavior of all other fluids in a damaged barrier, remaining for a very long time in the interstitial space. In the extra-axial lesions, the contrast moved freely and the return from the interstitial to the intravascular space was also unobstructed, since values decayed immediately after injection. For these reasons, the observation of scans after two hours of contrast injection might be useful for differential diagnosis in those cases where doubt exists.

Detection and mapping of endogenous receptors for carrier-immobilized constituents of glycoconjugates (lectins) by labelled (neo)glycoproteins and by affinity chromatography in human adult mesencephalon, pons, medulla oblongata and cerebellum

Different carrier-immobilized carbohydrate moieties were employed as tools to detect respective binding sites glycohistochemically and glycobiochemically. Besides ascertaining their presence the pattern of endogenous sugar receptors (lectins) in different regions of the human central nervous system was mapped to reveal any non-uniform expression. A strong and specific staining with biotinylated neoglycoproteins, exposing different sugar moieties as ligands, indicated the presence of sugar receptors in the nuclei, neuronal pathways and accessory structures such as ependyma cells, plexus chorioideus, intra- and extracerebral vessels and leptomeninges localized in the mesencephalon, in the pons, in the medulla oblongata and in the cerebellum. Significant differences were seen for various neuroanatomical regions like nerve cells in the basal and central regions of the nuclei pontis in the glycohistochemically detected level of expression of endogenous sugar receptors (lectins). The used approach with carbohydrate constituents of cellular glycoconjugates as ligands in search of specific receptors complemented studies on the localization of glycoconjugates with sugar-specific tools like plant lectins. Exemplary glycobiochemical investigations on the medulla oblongata and cerebellum were performed to investigate the molecular nature of sugar receptors detected glycohistochemically. Despite notable overall similarities, carbohydrate-binding proteins of differing molecular weight can be isolated from these two regions of the central nervous system, namely in the case of receptors with specificity to beta-galactoside termini, to N-acetyl-D-galactosamine and N-acetyl-D-glucosamine and to D-xylose. These combined glycohistochemical and glycobiochemical results serve as a guideline for exploring the physiological relevance of the detected regional differences.

Characterization of 5-hydroxytryptamine receptors in the cranial vasculature

The availability of selective compounds has made it possible to subdivide 5-hydroxytryptamine (5-HT) receptors into three distinct types, called 5-HT1-like, 5-HT2 and 5-HT3. The selective agonists at the three receptor types are, respectively, 5-carboxamidotryptamine, alpha-methyl-5-HT and 2-methyl-5-HT. While no selective antagonists are yet available for the 5-HT1-like receptors, some compounds, including ketanserin and MDL 72222, selectively antagonize 5-HT2 and 5-HT3 receptors respectively. Depending upon experimental conditions, 5-HT causes a constriction or dilatation of cerebral and extracerebral cranial vessels. Vascular contraction by 5-HT seems to be mediated primarily via 5-HT2 receptors (located mainly on large conducting vessels), though in several instances (for example, dog and human basilar arteries and porcine arteriovenous anastomoses; AVAs) 5-HT1-like receptors are involved in addition to or in place of 5-HT2 receptors. In the rabbit ear and external carotid arteries 5-HT may act directly on alpha-adrenoceptors. Arteriolar dilatation, leading to increased capillary ("nutrient") blood flow, occurs via 5-HT1-like receptors. However, the 5-HT1-like receptors on the arterioles and AVAs appear to be similar but not identical. Since a reduction of plasma 5-HT and opening of AVAs have been implicated in the pathophysiology of migraine, compounds acting on 5-HT1-like receptors to close the shunt vessels can be expected to have therapeutic activity in migraine.