Major Brain Arteries Research Articles

Abstract WP68: National Database Demonstrates Substantial Delays Between Non-Contrast CT and CT Angiography in Suspected Stroke Patients in 2023

Background: Prompt identification of large vessel occlusions (LVOs) leads to shorter door to thrombectomy times and better outcomes. In most stroke centers, both a non-contrast CT (CT) and CT angiography (CTA) are ordered simultaneously in patients suspected to have acute stroke. In some centers, a CT is performed first, and CTA is subsequently obtained if vessel imaging is deemed necessary. Methods : Data on 23,925 patients from 717 hospitals who underwent both CT and CTA imaging processed with Rapid software in the United States from Jan 1, 2023 to June 30, 2023 were queried to determine the time delay between CT and CTA. Rapid software is typically used to evaluate suspected stroke patients for occlusions of major brain arteries and salvageable tissue. Results : A delay greater than 15 minutes between CT and CTA occurred in 4,365 patients (18%). Among the 717 hospitals, 595 (83%) had a median delay of less than 15 minutes, 77 (11%) had 15-30 minute delays and 45 (6%) had greater than 30 minute median delays. Among the 595 high performing hospitals, 57% had greater than 15 minute delays in 10% or fewer patients, 33% of the hospitals had 11-33% of their patients with greater than 15 minute delays, and 10% had 34-50% of patients with greater than 15 minute delays. Conclusion : Nearly 20% of patients have a delay greater than 15 minutes between CT and CTA. Seventeen percent of hospitals had a median delay of greater than 15 minutes and 6% had more than a 30 minute median delay. Even among high performing hospitals, a substantial number of patients had more than 15 minutes delay suggesting these patients were moved off the scanner between scans. Education on reducing CT to CTA time in suspected stroke patients should be targeted to hospitals with substantial delays. Software to identify LVOs on non-contrast CT could significantly reduce the door to diagnosis time for LVOs.

Variation in blood viscosity based on the potential cause of stroke of undetermined etiology

Background: This study investigated potential differences in blood viscosity (BV) among patients with stroke of undetermined etiology, negative evaluation (SUDn), specifically those with potential atherothrombosis (SUDn-AT) and those with possible embolism (SUDn-E).Methods: This single-center study employed a retrospective observational design. The participants were patients over 20 years old with the SUDn stroke subtype who were admitted within 5 days of symptom onset. These patients were categorized as SUDn-AT or SUDn-E. Patients in the SUDn-AT group had nonsignificant stenosis (<50%) of a major brain artery relevant to their symptoms and exhibited one or more signs of systemic atherosclerosis, including atherosclerosis of at least one major brain artery other than those clinically relevant, coronary artery disease, and/or peripheral artery disease. For the SUDn-E group, the SUDn criteria from the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification system were strictly applied.Results: The final analysis included 153 patients, with 104 (68%) classified as SUDn-E and the remaining 32% as SUDn-AT. Patients in the SUDn-AT group had a higher systolic BV (P=0.012) and diastolic BV (P=0.020) than those in the SUDn-E group. Multivariable logistic regression analysis revealed that age (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.03–1.13; P=0.003), systolic BV (OR, 3.11; 95% CI, 1.41–6.85; P=0.005), and diastolic BV (OR, 1.08; 95% CI, 1.02–1.14; P=0.009) were associated with SUDn-AT.Conclusions: Within the TOAST system, two SUDn entities may be distinguishable, with potentially different underlying etiologies: atherothrombosis and embolic stroke of undetermined source.

Factors Associated With the Dilation of Perivascular Space in Healthy Elderly Subjects.

Background: The dilation of perivascular space (PVS) has been widely used to reflect brain degeneration in clinical brain imaging studies. However, PVS characteristics exhibit large differences in healthy subjects. Such variations need to be better addressed before PVS can be used to reflect pathological changes. In the present study, we aim to investigate the potential influence of several related factors on PVS dilation in healthy elderly subjects.Methods: One-hundred and three subjects (mean age = 59.5) were retrospectively included from a prospectively collected community cohort. Multi-modal high-resolution magnetic resonance imaging and cognitive assessments were performed on each subject. Machine-learning based segmentation methods were employed to quantify PVS volume and white matter hyperintensity (WMH) volume. Multiple regression analysis was performed to reveal the influence of demographic factors, vascular risk factors, intracranial volume (ICV), major brain artery diameters, and brain atrophy on PVS dilation.Results: Multiple regression analysis showed that age was positively associated with the basal ganglia (BG) (standardized beta = 0.227, p = 0.027) and deep white matter (standardized beta = 0.220, p = 0.029) PVS volume. Hypertension was positively associated with deep white matter PVS volume (standardized beta = 0.234, p = 0.017). Furthermore, we found that ICV was strongly associated with the deep white matter PVS volume (standardized beta = 0.354, p < 0.001) while the intracranial artery diameter was negatively associated with the deep white matter PVS volume (standardized beta = −0.213, p = 0.032).Conclusions: Intracranial volume has significant influence on deep white matter PVS volume. Future studies on PVS dilation should include ICV as an important covariate.

Shear-Induced Amyloid Aggregation in the Brain: V. Are Alzheimer's and Other Amyloid Diseases Initiated in the Lower Brain and Brainstem by Cerebrospinal Fluid Flow Stresses?

Amyloid-β (Aβ) and tau oligomers have been identified as neurotoxic agents responsible for causing Alzheimer’s disease (AD). Clinical trials using Aβ and tau as targets have failed, giving rise to calls for new research approaches to combat AD. This paper provides such an approach. Most basic AD research has involved quiescent Aβ and tau solutions. However, studies involving laminar and extensional flow of proteins have demonstrated that mechanical agitation of proteins induces or accelerates protein aggregation. Recent MRI brain studies have revealed high energy, chaotic motion of cerebrospinal fluid (CSF) in lower brain and brainstem regions. These and studies showing CSF flow within the brain have shown that there are two energetic hot spots. These are within the third and fourth brain ventricles and in the neighborhood of the circle of Willis blood vessel region. These two regions are also the same locations as those of the earliest Aβ and tau AD pathology. In this paper, it is proposed that cardiac systolic pulse waves that emanate from the major brain arteries in the lower brain and brainstem regions and whose pulse waves drive CSF flows within the brain are responsible for initiating AD and possibly other amyloid diseases. It is further proposed that the triggering of these diseases comes about because of the strengthening of systolic pulses due to major artery hardening that generates intense CSF extensional flow stress. Such stress provides the activation energy needed to induce conformational changes of both Aβ and tau within the lower brain and brainstem region, producing unique neurotoxic oligomer molecule conformations that induce AD.

Unruptured Intracranial Aneurysms.

Unruptured Intracranial Aneurysms.

Stroke: Just a Chemistry

Stroke is a significant health issue with its neuropathological mechanisms requiring better understanding. Within the course of ischemic stroke, obstruction of a major brain artery results in an abrupt blood flow limitation below a critical threshold and focal ischemic brain insult arises. Chemical shift imaging using magnetic resonance spectroscopy and more advanced imaging methods have recently provided some novel insights into the chemistry of stroke. Given the fact that stroke disturbs the normal brain chemistry, assessing and perhaps targeting the metabolic pathways ought to be a practical and useful approach to better understand the neurobiochemical aspects of stroke. This perspective paper focuses on the evolving dimensions of neurochemical research in stroke.[GMJ.2016;5(2):49-55]

MR Angiography at 7T to Visualize Cerebrovascular Territories.

There is considerable amount of interindividual variability in the size and location of the vascular territories of the major brain arteries. More data are needed to assess the amount of variability and the possible implications for further research and patient care. Arterial spin labeling (ASL) magnetic resonance imaging has been applied in various forms to facilitate noninvasive imaging of cerebrovascular flow territories, but it requires the definition of the flow territory of interest prior to image acquisition. Assessing the vascular territories of the major brain territories by using ultra-high-field time-of-flight (TOF) magnetic resonance angiography. We have developed an alternative method to ASL by simulating cerebrovascular dye injections. Following bias field normalization and segmentation of the vessels from 7 Tesla TOF imaging, a virtual model of the arterial vessel tree was generated and a simulation of dye dispersion into the brain tissue was performed. The results provided by our method are consistent with the data obtained by autoptic dye injection studies in 23 human beings by van der Zwan in 1993. Further technical improvements in imaging and segmentation techniques will improve the accuracy of the method and will facilitate the delineation of flow territories after image acquisition on even smaller subtrees of the cerebral vasculature.

Imaging of α7 nicotinic acetylcholine receptors in brain and cerebral vasculature of juvenile pigs with [(18)F]NS14490.

BackgroundThe α7 nicotinic acetylcholine receptor (nAChR) is an important molecular target in neuropsychiatry and oncology. Development of applicable highly specific radiotracers has been challenging due to comparably low protein expression. To identify novel ligands as candidates for positron emission tomography (PET), a library of diazabicyclononane compounds was screened regarding affinity and specificity towards α7 nAChRs. From these, [18F]NS14490 has been shown to yield reliable results in organ distribution studies; however, the radiosynthesis of [18F]NS14490 required optimization and automation to obtain the radiotracer in quantities allowing dynamic PET studies in piglets.MethodsAutomated radiosynthesis of [18F]NS14490 has been performed by [18F]fluorination with the tosylate precursor in the TRACERlab™ FX F-N synthesis module (Waukesha, WI, USA). After optimization, the radiochemical yield of [18F]NS14490 was consistently approximately 35%, and the total synthesis time was about 90 min. The radiotracer was prepared with >92% radiochemical purity, and the specific activity at the end of the synthesis was 226 ± 68 GBq μmol−1. PET measurements were performed in young pigs to investigate the metabolic stability and cerebral binding of [18F]NS14490 without and with administration of the α7 nAChR partial agonist NS6740 in baseline and blocking conditions.ResultsThe total distribution volume relative to the metabolite-corrected arterial input was 3.5 to 4.0 mL g−1 throughout the telencephalon and was reduced to 2.6 mL g−1 in animals treated with NS6740. Assuming complete blockade, this displacement indicated a binding potential (BPND) of approximately 0.5 in the brain of living pigs. In addition, evidence for specific binding in major brain arteries has been obtained.Conclusion[18F]NS14490 is not only comparable to other preclinically investigated PET radiotracers for imaging of α7 nAChR in brain but also could be a potential PET radiotracer for imaging of α7 nAChR in vulnerable plaques of diseased vessels.

Abstract 3362: Neurological Deterioration And Stroke Recurrence In The Acute Phase Of Japanese Minor Stroke ∼ Fukuoka Stroke Registry ∼

Background &amp; Purpose: A neurological deterioration in the acute phase can be associated with a bad outcome even in the minor stroke. We investigated the predictive factors for an acute neurological deterioration in minor stroke. Subjects &amp; Methods: Among the consecutive 3062 stroke patients who were admitted to the 7 stroke centers in Fukuoka prefecture Japan within 7 days after the onset, 2113 patients with acute ischemic stroke with the initial NIH stroke scale score of 7 or less and preclinical modified Rankin scale of 0 or 1 were included in the present study. We observed a neurological deterioration (a NIH stroke scale score worsening of ≥1-point), stroke recurrence, or any death during the first 21 hospital days. Results: A neurological deterioration with or without stroke recurrence was observed in 338 (16%) patients. Baseline NIH stroke scale score was not different between patients with and without a neurological deterioration. With regard to the TOAST classification, a neurological deterioration was most frequent in Large-artery atherosclerosis (18.3%), followed by Others (18.2%), Cardioembolism (15.6%), and Small-vessel occlusion (12.2%) in order. In accordance with the site of ischemic lesions, a neurological deterioration was most frequent in patients with both cortex or cerebellar lesions and deep perforating artery lesions (20.2%). A preexisting warfarin use was less frequent (6.8% vs 10%, p=0.0624), diabetes mellitus (42% vs 32%, p=0.0007) and a stenosis of ≥50% in the major brain artery (35% vs 28%, p=0.0133) were more frequent, and the initial values of low density lipoprotein (LDL) cholesterol (122.1±36.5 vs 116.6±34.7 mg/dl, p=0.0100), blood glucose (144.9±66.5 vs 138.9±60.1 mg/dl, p=0.0969), and HbA1c (6.05±1.42 vs 5.91±1.23, p=0.0801) were higher in patients with than without a neurological deterioration. Maximum intima-media thickness of the common carotid artery was relatively thicker in patients with than without a neurological deterioration (1.87±1.55 vs 1.69±0.97 mm, p=0.0624). On multivariate analysis, a stenosis of ≥50% in the major brain artery (OR, 1.40; 95%CI 1.07∼1.85), ischemic lesions including deep perforating artery area (OR, 1.47; 95%CI, 1.10∼1.96), LDL cholesterol (OR, 1.00; 95%CI, 1.00∼1.01), and diabetes mellitus (OR 1.70, 95%CI 1.21∼2.39) had a positive association, and preexisting warfarin use (OR 0.61, 95%CI 0.39∼0.98) had a negative association with a neurological deterioration. Conclusions: The major brain artery stenotic lesion, the site of ischemic lesions, LDL cholesterol, and diabetes mellitus were significant predictor for a neurological deterioration in the acute phase of minor stroke. A preexisting warfarin use might decrease the risk of a neurological deterioration.

Abstract 3984: Neurological Deterioration And Stroke Recurrence In The Acute Phase Of Ischemic Stroke In The Deep Perforating Artery Territory ∼ Fukuoka Stroke Registry ∼

Background &amp; Purpose: A neurological deterioration in the acute phase can be associated with a bad outcome even in the minor stroke. We investigated the predictive factors for an acute neurological deterioration or stroke recurrence in the deep perforating artery territory stroke. Subjects &amp;Methods: Among the consecutive 3062 stroke patients who were admitted to the 7 stroke centers in Fukuoka prefecture Japan within 7 days after the onset, 1141 patients with infarcts supplied by deep perforating artery with the initial NIH stroke scale score of 7 or less and preclinical modified Rankin scale of 0 or 1 were included in the present study. We observed a neurological deterioration (a NIH stroke scale score worsening of ≥1-point), stroke recurrence, or any death during the first 21 hospital days. Results: A neurological deterioration with or without stroke recurrence was observed in 196 (17.2%) patients. Baseline NIH stroke scale score was not different between patients with and without a neurological deterioration (2.7±1.9 vs 2.7±1.7). With regard to the TOAST classification, a neurological deterioration was most frequent in Large-artery atherosclerosis (27.8%), and was least frequent in Small-vessel occlusion (12.3%). The site of ischemic lesions was not associated with a neurological deterioration. A preexisting warfarin use was less frequent (7% vs 11%, p=0.0472), dyslipidemia (62% vs 53%, p=0.0182) and a stenosis of ≥50% in the major brain artery (26% vs 16%, p=0.0009) were more frequent, the values of low density lipoprotein (LDL) cholesterol was higher (124.6±36.3 vs 119.4±33.8 mg/dl, p=0.0495) and high density lipoprotein (HDL) was lower (50.7±14.1 vs 53.8±14.4 mg/dl, p=0.0056) in patients with than without a neurological deterioration. Diabetes mellitus was relatively more frequent in patients with than without a neurological deterioration (43% vs 36%, p=0.0669). On multivariate analysis, a stenosis of ≥50% in the major brain artery (OR, 2.44; 95%CI 1.44∼4.17) had a positive association with a neurological deterioration. Initial HDL values (OR, 0.99; 95%CI, 0.97∼1.00) and preexisting warfarin use (OR, 0.38; 95%CI, 0.13∼1.11) tended to be negatively associated with a neurological deterioration. Conclusions: The major brain artery stenotic lesion was a significant predictor for an acute neurological deterioration or stroke recurrence in the deep perforating artery territory stroke. A preexisting warfarin use and high HDL value might decrease the risk of a neurological deterioration.

Early stroke treatment with IV t-PA associated with early recanalization

Purpose Time from stroke onset to treatment (OTT) is potentially an important factor affecting subsequent outcome in patients treated with t-PA. The aim of the study was to assess the correlation between OTT and early recanalization rate after IV-t-PA therapy. Methods Consecutive stroke patients treated with t-PA within 3 h of onset were prospectively studied. Patients with major brain artery occlusion on MRA before t-PA infusion were enrolled. The correlation between OTT and the early recanalization rate within 1 h after t-PA infusion was determined. Results 102 patients (M1 occlusion, 41 patients; M2, 19; ICA, 31; BA, 8; and PCA, 3) were enrolled. Follow-up MRA within 1 h after t-PA infusion showed early recanalization in 42 (41.2%) patients (complete in 13 patients, partial in 29). The early recanalization rate was 53.8% with OTT ≤ 100 min, 57.1% in 101–110 min, 50.0% in 111–120 min, 63.6% in 121–130 min, 33.3% in 131–140 min, 30.0% in 141–150 min, 36.4% in 151–160 min, 18.2% in 161–170 min, and 32.0% in 171–180 min. OTT was negatively correlated with the early recanalization rate ( r = −0.767, P = 0.0301). After adjusting the presence of age (> 74), ICA occlusion, baseline NIHSS score (< 10), and glucose (> 150 mg/dl), adjusted OR for early recanalization of OTT ≤ 130 min against OTT > 130–180 min was 2.97 (95% CI 1.27–6.96, P = 0.012). Conclusion Early recanalization depended on time from stroke onset to IV-t-PA administration. Thus, t-PA should be given to acute stroke patients as soon as possible.

Recanalization within One Hour after Intravenous Tissue Plasminogen Activator Is Associated with Favorable Outcome in Acute Stroke Patients

Background/Aim: Early recanalization after tissue plasminogen activator (t-PA) infusion greatly improves outcome in stroke patients. However, the time threshold of early recanalization for a favorable outcome remains unclear. The aim of this study was to assess patient outcome 3 months after t-PA therapy among patients with early, delayed and without recanalization. Methods: Consecutive patients with major brain artery occlusion on magnetic resonance angiography (MRA) before t-PA infusion were enrolled. We divided the patients into 3 groups according to the findings of follow-up MRA 1 and 24 h after t-PA: the early group who had recanalization within 1 h after t-PA; the delayed group who had recanalization between 1 and 24 h, and the no recanalization group. We then assessed the outcomes (modified Rankin score 0–1) 3 months after t-PA therapy among the 3 groups. Results: A total of 92 patients (53 men, mean age 75.8 ± 10.3 years) were enrolled. A favorable outcome was most frequently observed in the early group (n = 39, 40.6%), followed by the delayed group (n = 25, 18.2%), and the no recanalization group (n = 28, 10.5%; p = 0.037). After adjusting for age, atrial fibrillation and NIHSS score, the adjusted OR for early recanalization when compared with no recanalization was 7.11 (95% CI 1.177–43.063; p = 0.032) for a favorable outcome, while the adjusted OR for delayed recanalization was 1.75 (95% CI 0.104–29.356; p = 0.698). Conclusion: Early recanalization within 1 h after intravenous t-PA is associated with a favorable outcome in stroke patients.

The combination of elevated BNP and AF as a predictor of no early recanalization after IV-t-PA in acute ischemic stroke

Background and purpose In acute stroke patients treated with intravenous tissue plasminogen activator (t-PA), early recanalization can improve patient outcome. Heart failure may result in reduction of brain perfusion, which limits the ability of the blood stream to wash out emboli. Brain natriuretic peptide (BNP) is used as a biological marker of heart failure. Most stroke patients with atrial fibrillation (AF) have elevated BNP levels. We investigated the relationships of plasma BNP levels before t-PA infusion and AF with early recanalization after t-PA infusion. Methods Patients with a major brain artery occlusion were studied prospectively. MRAs were performed before and within 60 min after t-PA infusion. The relationship between BNP levels before t-PA infusion and the presence of AF with early recanalization was examined. Results Seventy-nine patients (49 men; mean age, 75.5 ± 10.4 years; ICA occlusion in 25 patients, M1 in 32, M2 in 13, PCA in 3, and BA in 6) were enrolled. Follow-up MRA within 60 min after t-PA infusion revealed recanalization in 35 (44.3%) patients and no recanalization in 44 (55.7%). Patients with AF (57.1% vs. 75.0%, P = 0.0294) and BNP > 150 pg/dl (39.0% vs. 73.7%, P = 0.0019) less frequently had early recanalization than those without AF and with BNP ≤ 150 pg/dl. The combination of AF and BNP > 150 pg/ml was a useful predictor for no early recanalization (positive predictive value, 79.4%; negative predictive value, 62.2%; sensitivity, 61.4%; specificity, 80.0%). Conclusion The presence of AF and elevated BNP was associated with no early recanalization after IV-t-PA therapy. We should need further study to ascertain its predictive ability.

Early Recanalization Rate of Major Occluded Brain Arteries after Intravenous Tissue Plasminogen Activator Therapy Using Serial Magnetic Resonance Angiography Studies

Purpose: The present study investigated early recanalization rate of major occluded arteries after tissue plasminogen activator (t-PA) infusion using serial magnetic resonance angiography (MRA) studies. Methods: Consecutive stroke patients treated with t-PA within 3 h of onset were prospectively studied. Four serial MRA studies were conducted: before, immediately, 24 h and 5–7 days after t-PA infusion. Results: Initial MRA demonstrated occluded brain arteries in 64 patients: M1 occlusion, 30 patients; M2, 12, and internal carotid artery (ICA), 22. Combining M1 and M2 occlusion, the recanalization rates (complete and partial) were 52.3% (19.0 and 33.3%) within 1 h, 80.9% (47.6 and 33.3%) at 24 h and 87.8% (73.2 and 14.6%) 7 days after t-PA infusion. However, the recanalization rate of ICA occlusion was 31.8% (4.5 and 27.3%) within 1 h, 51.1% (14.3 and 47.6%) at 24 h and 66.7% (38.9 and 27.8%) 7 days after t-PA infusion. Complete recanalization rate at 24 h and 7 days was lower in ICA occlusion than M1 and M2 occlusion (p = 0.014 and p = 0.016). Conclusion: Within 1 h after t-PA infusion, approximately half the patients with major arteries occlusion had early recanalization. ICA occlusion is resistant to intravenous t-PA therapy compared with middle cerebral artery occlusion.

Occurrence and Clinical Impact of Microembolic Signals (MES) in Patients with Chronic Cardiac Diseases and Atheroaortic Plaques - A Systematic Review

In various cardiac diseases, thrombembolism constitutes a major risk, and in these patients clinically silent microembolic signals (MES) are detectable within the transcranial Doppler frequency spectrum (TCD) of the major brain arteries. MES are already an accepted surrogate parameter of the future risk of stroke in patients with carotid artery stenosis. The aim of this review is to summarize and evaluate the data about occurence and clinical impact of MES in patients with chronic cardiac diseases and to clarify whether cardiogenic MES can serve as a surrogate parameter of the heart's future thrombembolic risk as well. We performed a systematic MEDLINE search and reviewed the currently available literature about chronic cardiac diseases and atheroaortic plaques leading to MES apart from cardiosurgical procedures. The cardiac conditions producing MES are heterogenous and therefore the prevalence of MES is highly variable. The data in patients with acute or after myocardial infarction, endocarditis, patent foramen ovale, mitral valve prolapse, dilatative cardiomyopathy and intracardiac thrombus is promising but only small patient cohorts have been investigated by means of TCD in these categories. MES in atrial fibrillation, or derived from atheroaortic plaques, have been investigated more intensively, but again larger cohorts need to be explored to draw firm conclusions. In all cardiac diseases there is a lack of large prospective studies allowing to reliably correlating MES with clinical events. Compared to carotid artery disease, the current knowledge about the impact of cardiogenic MES on the patient's risk is sparse. This should encourage the clinical research in this promising field.

Protective effect of anthocyanins in middle cerebral artery occlusion and reperfusion model of cerebral ischemia in rats

Ischemic stroke results from a transient or permanent reduction in cerebral blood flow that is restricted to the territory of a major brain artery. The major pathobiological mechanisms of ischemia/reperfusion injury include excitotoxicity, oxidative stress, inflammation, and apoptosis. In the present report, we first investigated the protective effects of anthocyanins against focal cerebral ischemic injury in rats. The pretreatment of anthocyanins (300 mg/kg, p.o.) significantly reduced the brain infarct volume and a number of TUNEL positive cells caused by middle cerebral artery occlusion and reperfusion. In the immunohistochemical observation, anthocyanins remarkably reduced a number of phospho-c-Jun N-terminal kinase (p-JNK) and p53 immunopositive cells in the infarct area. Moreover, Western blotting analysis indicated that anthocyanins suppressed the activation of JNK and up-regulation of p53. Thus, our data suggested that anthocyanins reduced neuronal damage induced by focal cerebral ischemia through blocking the JNK and p53 signaling pathway. These findings suggest that the consumption of anthocyanins may have the possibility of protective effect against neurological disorders such as brain ischemia.

Regional distribution of cyclooxygenase-3 mRNA in the rat central nervous system

We determined COX-3 mRNA expression in regions of the rat central nervous system (CNS). On a regional basis, levels were the highest in choroid plexus and spinal chord followed by pituitary gland, hypothalamus, hippocampus, medulla, cerebellum, and cortex. COX-3 mRNA levels were higher in major brain arteries, and dramatically higher in brain microvessels. Our results suggest that the expression pattern of COX-3 mRNA in the rat CNS primarily relates to the vascular density of a given region.

High-flow excimer laser-assisted extra-intracranial and intra-intracranial bypass

High-flow revascularization of the brain is hampered by the fact that temporary occlusion of a major brain artery, necessary to make the distal end-to-side anastomosis, may result in brain ischemia. The Excimer laser-assisted nonocclusive anastomosis technique circumvents this problem. After connecting donor and recipient vessels, an Excimer laser catheter, introduced by way of an artificial side branch, creates a hole at the anastomosis site. When the catheter is withdrawn, a round full-thickness portion of the recipient artery is removed. When the artificial side branch is occluded with a hemoclip the anastomosis is completed. The recipient vessel stays open during the procedure. In 90 patients a high-flow bypass was made. In 90% several types of extra-intracranial bypasses were created, and in 10% several types of intra-intracranial bypasses were created. Flow recordings by way of an ultrasound device intraoperatively and with a magnetic resonance (MR) flow program postoperatively show the bypasses to have a real “high flow” character. Complications related to this high-flow bypass procedure and ways to prevent them are presented.

Upregulation of the Enzyme Chain Hydrolyzing Extracellular ATP after Transient Forebrain Ischemia in the Rat

A short ischemic period induced by the transient occlusion of major brain arteries induces neuronal damage in selectively vulnerable regions of the hippocampus. Adenosine is considered to be one of the major neuroprotective substances produced in the ischemic brain. It can be released from damaged cells, but it also could be generated extracellularly from released ATP via a surface-located enzyme chain. Using the rat model of global forebrain ischemia, we applied a short (10 min) transient interruption of blood flow and studied the distribution of ectonucleotidase activities in the hippocampus. Northern hybridization of mRNA isolated from hippocampi of sham-operated and ischemic animals revealed an upregulation of ectoapyrase (capable of hydrolyzing nucleoside 5'-tri- and diphosphates) and ecto-5'-nucleotidase (capable of hydrolyzing nucleoside 5'-monophosphates). A histochemical analysis that used ATP, UTP, ADP, or AMP as substrates revealed a strong and selective increase in enzyme activity in the injured areas of the hippocampus. Enhanced staining could be observed first at 2 d. Staining increased within the next days and persisted at 28 d after ischemia. The spatiotemporal development of catalytic activities was identical for all substrates. It was most pronounced in the CA1 subfield and also could be detected in the dentate hilus and to a marginal extent in CA3. The histochemical staining corresponded closely to the development of markers for reactive glia, in particular of microglia. The upregulation of ectonucleotidase activities implies increased nucleotide release from the damaged tissue and could play a role in the postischemic control of nucleotide-mediated cellular responses.

AVERAGE: a Windows® program for automated analysis of event related cerebral blood flow

Functional transcranial Doppler sonography (fTCD) is used to measure changes in brain perfusion during different states of brain activity by evaluating flow velocities within the major brain arteries. We developed a computer program called AVERAGE which can be used with various TCD devices and allows for subtle quantitative off-line analysis of Doppler flow signals. AVERAGE supports data transformation, heart beat analysis, noise reduction, trigger signal and marker modification, artifact analysis and artifact rejection, as well as data reduction. Perfusion differences and their time course within two different arteries can be analyzed by parametric and non parametric statistical methods. This is important, for instance, in studies on hemispherical dominance during mental task processing. Each data processing step is supported by graphical output. If investigated bilaterally with interhemispheric analysis even minimal activations can reliably be detected and quantified with a sensitivity known from positron emission tomography approaches.