Hypoxic-ischaemic encephalopathy is associated with regional changes in cerebral blood flow velocity and alterations in cardiovascular function

Pig-to-primate cardiac xenografts surviving beyond the period of hyperacute rejection succumb after 3-4 days to a secondary immunologic response characterized by xenograft infiltration with NK cells and macrophages. Circulating baboon mononuclear cells contain NK cell precursors which mediate lysis of porcine endothelium by two distinct mechanisms: antibody-dependent cellular cytotoxicity and lymphokine activation. IL-2 activated NK lysis of porcine endothelium was 2.4-fold stronger than lysis occurring following engagement of FcRIII by xenoreactive IgG. IL-2 augmented NK lysis involved interactions between CD2 and CD49d on baboon NK cells and their respective ligands on porcine endothelium, since NK lysis was reduced either by using Mabs against CD2, CD49d, or porcine VCAM, or by treating endothelial cells with PIPLC to cleave GPI-linked molecules. These results imply that interactions between accessory molecule receptor-ligand pairs on primate NK cells, macrophages and porcine endothelium are of critical importance in delayed xenograft rejection.     

Olfactory-evoked regional cerebral blood flow in Alzheimer's disease.

Olfaction is impaired in Alzheimer's disease (AD). It was hypothesized that AD would reduce olfactory-evoked perfusion in mesial temporal olfactory (piriform) cortex, where neuropathology begins. Seven AD patients and 8 elderly controls (ECs) underwent olfactory threshold and identification tests and olfactory stimulation during positron emission tomography. Odor identification was impaired in AD, but threshold was not. Olfactory stimulation in ECs activated right and left piriform areas and right anterior ventral temporal cortex. AD patients had less activation in right piriform and anterior ventral temporal cortex but not in the left piriform area. Although orbital cortex did not activate in ECs, there was a significant between-groups difference in this area. Right piriform activation correlated with odor identification. Impaired odor identification likely reflects sensory cortex dysfunction rather than cognitive impairment. Given olfactory bulb projections to the mesial temporal lobe, olfactory stimulation during functional imaging might detect early dysfunction in this region. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluation of regional cerebral blood flow in massive intracerebral calcifications

Fahr's disease is histopathologically characterized by massive bilateral calcifications of the cerebral basal ganglia, the dentate nuclei of the cerebellum and both the cerebral and cerebellar cortices. We report a case of Fahr's disease in which a 99mTc-hexamethyl-propylenamine oxime (99mTc-HMPAO) brain SPECT study was used to evaluate regional cerebral blood flow to the calcified regions. There was markedly decreased perfusion to the basal ganglia bilaterally as well as decreased perfusion to the cerebral cortices that correlated well with the patient's clinical condition.     

Selective effects of the endogenous cannabinoid arachidonylethanolamide (anandamide) on regional cerebral blood flow in the rat

Chronic focal epilepsy is associated with synaptic plasticity and growth of new connections. Brain-derived neurotrophic factor (BDNF) is associated with each of these processes in normal brain and shows acute up-regulation in models of generalized epilepsy. Here, using an experimental model of focal epilepsy, we show persistent up-regulation of BDNF mRNA, independent of that of other growth factors, in association with the development and persistence of chronic seizures. In situ hybridization histochemistry revealed that rats perfused within 2-3 days after seizure onset had widespread increases in BDNF mRNA levels in the neocortex. Rats perfused at later times, however, showed focal up-regulation of BDNF mRNA at the injection site and down-regulation in a surrounding cortical zone. Nerve growth factor and neurotrophin-3 mRNAs were not significantly altered. These reciprocal changes in BDNF gene expression in the epileptic focus and the cortical surround may contribute to plastic changes in epileptic neuronal circuits that accompany the transition from acute to chronic epilepsy. BDNF down-regulation in the surround is likely to be associated with the inhibitory surround that hampers seizure spread, but facilitates the persistence of a chronic epileptic focus.     

Neuropsychological dysfunction in depression: the relationship to regional cerebral blood flow

The relationship between neuropsychological test performance and regional cerebral blood flow (rCBF) was examined in 29 patients meeting Research Diagnostic Criteria (RDC) for major depression. Following a comprehensive neuropsychological assessment two subsets of tests, comprising tests that discriminated between patients and controls or between patients with varying degrees of global cognitive impairment, were selected. These subtests were entered into a principal components analysis (PCA) which generated a two-factor solution, accounting for 50% of the overall variance in test scores. Individual patient loadings on each of these factors were subsequently correlated with regional cerebral blood flow (rCBF), as measured by positron emission tomography (PET). Both factors demonstrated significant correlations with rCBF in the medial prefrontal cortex and frontal polar cortex while for each factor there were also unique patterns of correlations with posterior brain regions. The findings provide additional evidence that neuropsychological deficits in depression are associated with abnormalities in regional brain function and in particular with the function of the medial prefrontal cortex.     

Reduction of regional cerebral blood flow by melatonin in young rats

Melatonin (10 ng) was subcutaneously administered to 14-day-old Sprague-Dawley rats. Regional blood flow (rCBF) was measured in 22 anatomically defined structures 20 min later using iodo[14C]antipyrine and quantitative autoradiography. rCBF was markedly reduced in the cerebral areas supplied by circle of Willis and the basilar arteries. Melatonin also significantly decreased blood flow to choroid plexuses. These findings suggest that circulating melatonin may contribute to regulation of cerebral blood flow and brain fluid balance.     

Ocular and regional cerebral blood flow in aging Fischer-344 rats

Vascular remodeling and changes in vascular responsiveness occur in the rat cerebrum with old age. This includes reductions in cerebral arteriolar numerical density, cross-sectional area, distensibility, the relative proportion of distensible elements in the cerebral arteriolar wall, and reduced endothelium-dependent relaxation. The purpose of this study was to test the hypothesis that old age results in an increase in vascular resistance and, correspondingly, a decrease in blood flow to ocular, regional cerebral, and spinal tissue in the rat. Blood flow was measured in the eye, olfactory bulb, left and right cerebrum, pituitary gland, midbrain, pons, cerebellum, medulla, and spinal cord of juvenile (2-mo-old, n = 6), adult (6-mo-old, n = 7), and aged (24-mo-old, n = 7) male Fischer-344 rats. Arterial pressure and blood flow were used to calculate vascular resistance. Vascular resistance in the eye of aged rats (6.03 +/- 1.08 mmHg . ml-1 . min . 100 g) was higher than that in juvenile (3.83 +/- 0.38 mmHg . ml-1 . min . 100 g) and adult rats (3.12 +/- 0.24 mmHg . ml-1 . min . 100 g). Similarly, resistance in the pons of older rats (2.24 +/- 0.55 mmHg . ml-1 . min . 100 g) was greater than in juvenile (0.66 +/- 0.06 mmHg .ml-1 . min . 100 g) and adult rats (0.80 +/- 0.11 mmHg . ml-1 . min . 100 g). In contrast, vascular resistance in the pituitary gland was lower in the aged rats (juvenile, 3.09 +/- 0.22; adult, 2.79 +/- 0.42; aged, 1.73 +/- 0.32 mmHg . ml-1 . min . 100 g, respectively). Vascular resistance was not different in other cerebral tissues or in the spinal cord in the aged rats. These data suggest that regional cerebral and spinal blood flow and vascular resistance remain largely unchanged in conscious aged rats at rest but that elevations in ocular vascular resistance and, correspondingly, decreases in ocular perfusion with advanced age could have serious adverse effects on visual function.     

Effect of hyperventilation on regional cerebral blood flow in head-injured children

OBJECTIVES: To study cerebral blood flow and cerebral oxygen consumption in severe head-injured children and also to assess the effect of hyperventilation on regional cerebral blood flow. DESIGN: Prospective cohort study. SETTING: Pediatric intensive care unit at a tertiary-level university children's hospital. PATIENTS: Twenty-three children with isolated severe brain injury, whose admission Glasgow Coma Scores were <8. INTERVENTIONS: PaCO2 was adjusted by altering minute ventilation. Cerebral metabolic measurements were made at three levels of PaCO2 (>35, 25 to 35, and <25 torr [>4.7, 3.3 to 4.7, and <3.3 kPa]) after allowing 15 mins for equilibrium. MEASUREMENTS AND MAIN RESULTS: Thirty-eight studies (each study consisting of three sets of measurements at different levels of PaCO2) were performed on 23 patients. At each level of PaCO2, the following measurements were made: xenon-enhanced computed tomography scans; cerebral blood flow; intracranial pressure; jugular venous bulb oxygen saturation; mean arterial pressure; and arterial oxygen saturation. Derived variables included: cerebral oxygen consumption; cerebral perfusion pressure; and oxygen extraction ratio. Cerebral blood flow decreased below normal after head injury (mean 49.6 +/- 14.6 mL/min/100 g). Cerebral oxygen consumption decreased out of proportion to the decrease in cerebral blood flow; cerebral oxygen consumption was only a third of the normal range (mean 1.02 +/- 0.59 mL/min/100 g). Neither cerebral blood flow nor cerebral oxygen consumption showed any relationship to time after injury, Glasgow Coma Score at the time of presentation, or intracranial pressure. The frequency of one or more regions of ischemia (defined as cerebral blood flow of <18 mL/min/100 g) was 28.9% during normocapnia. This value increased to 73.1% for PaCO2 at <25 torr. CONCLUSIONS: Severe head injury in children produced a modest decrease in cerebral blood flow but a much larger decrease in cerebral oxygen consumption. Absolute hyperemia was uncommon at any time, but measured cerebral blood flow rates were still above the metabolic requirements of most children. The clear relationship between the frequency of cerebral ischemia and hypocarbia, combined with the rarity of hyperemia, suggests that hyperventilation should be used with caution and monitored carefully in children with severe head injuries.     

Effect of early pregnancy on maternal regional cerebral blood flow

OBJECTIVE: The purpose of this study was to assess the effect of early pregnancy on maternal regional cerebral blood flow. STUDY DESIGN: We studied 10 pregnant women at 7 to 19 weeks' gestation by the xenon 133 washout technique by means of single-photon emission computed tomography the day before the abortion was induced and then again at a mean of 42.8 days after the abortion. RESULTS: Blood flow in the cerebral hemispheres decreased after the abortion, with a decline of 8.1% (p < 0.001). Each regional decrease was as follows: 7.6% (p < 0.01) in the frontal lobe, 9.1% (p < 0.01) in the temporal lobe, 12.9% (p < 0.001) in the parietal lobe, 9.8% (p < 0.01) in the basal ganglia, and 16.7% (p < 0.001) in the cerebellum. There was no significant difference in blood flow in the occipital lobe before versus after the abortion. CONCLUSION: Maternal regional cerebral blood flow was increased in early pregnancy compared with the nonpregnant state, except in the occipital lobe.     

Chronic schizophrenia: validity of the study of regional cerebral blood flow through cerebral SPECT

OBJECTIVE: To check the validity of the diagnostic test in schizophrenia. MATERIAL AND METHODS: The cerebral blood flow (CBF) characteristics were assessed by means of single photon emission tomography (SPECT) in 24 patients with schizophrenia and 20 normal control subjects. Analysis of sensitivity, specificity and the Youden rate was made of certain RCBF patterns chosen in terms of the cerebral regions between which the greatest differences were observed according to the diagnosis, schizophrenia vs control. RESULTS: Schizophrenia vs control: sensitivity = 58.33%; specificity = 95%; positive predictive value = 93.33% and overall efficiency = 53.33%. CONCLUSIONS: Cerebral SPECT is valid in the discrimination between patients diagnosed with schizophrenia and control subjects, taking the diagnostic judgement of the psychiatrist as the gold standard, and the RCBF pattern that displays the best coefficient is hypoperfusion, in one or several of the regions: right frontal/left frontal/right parietal/thalamus: sensitivity = 58.33%; specificity = 95%; positive predictive value = 93.33% and overall efficiency = 53.33%.     

Age-related changes in regional cerebral blood flow during working memory for faces

Young and old adults underwent positron emission tomography during the performance of a working memory task for faces (delayed match-to-sample), in which the delay between the sample and choice faces was varied from 1 to 21 s. Reaction time was slower and accuracy lower in the old group, but not markedly so. Values of regional cerebral blood flow (rCBF) were analyzed for sustained activity across delay conditions, as well as for changes as delay increased. Many brain regions showed similar activity during these tasks in both young and old adults, including left anterior prefrontal cortex, which had increased rCBF with delay, and ventral extrastriate cortex, which showed decreased rCBF with delay. However, old adults had less activation overall and less modulation of rCBF across delay in right ventrolateral prefrontal cortex than did the young adults. Old adults also showed greater rCBF activation in left dorsolateral prefrontal cortex across all WM delays and increased rCBF at short delays in left occipitoparietal cortex compared to young adults. Activity in many of these regions was differentially related to performance in that it was associated with decreasing response times in the young group and increasing response times in the older individuals. Thus despite the finding that performance on these memory tasks and associated activity in a number of brain areas are relatively preserved in old adults, differences elsewhere in the brain suggest that different strategies or cognitive processes are used by the elderly to maintain memory representations over short periods of time.     

Diminished regional cerebral blood flow response to vibration in patients with blepharospasm

Mutations of the human Patched gene ( PTCH ) have been identified in individuals with the nevoid basal cell carcinoma syndrome (NBCCS) as well as in sporadic basal cell carcinomas and medulloblastomas. We have isolated a homologue of this tumour suppressor gene and localized it to the short arm of chromosome 1 (1p32.1-32.3). Patched 2 ( PTCH2 ) comprises 22 coding exons and spans approximately 15 kb of genomic DNA. The gene encodes a 1203 amino acid putative transmembrane protein which is highly homologous to the PTCH product. We have characterized the genomic structure of PTCH2 and have used single-stranded conformational polymorphism analysis to search for mutations in PTCH2 in NBCCS patients, basal cell carcinomas and in medulloblastomas. To date, we have identified one truncating mutation in a medulloblastoma and a change in a splice donor site in a basal cell carcinoma, suggesting that the gene plays a role in the development of some tumours.     

Assessment of thalamic regional cerebral blood flow in patients with cerebrovascular disease

The thalamus is believed to play an integrative role in the central nervous system. In the present study, thalamic rCBF was measured in 65 CVD patients and 15 normal volunteers by stable Xe/CT scanning. ROIs were chosen in the thalamic slice at a level 5cm over the OM line, and mean CBF was 7 cm over the OM line. The clinical factors focused on in multiple regression analysis were: age (A), sex (Se), stage from onset (St), lesion side (Sd); unilaterality or bilaterality, size (Sz) thalamic lesion (Tl). GCS (G), HDS-R (H); Hasegawa dementia score (revised), symptoms (Ss) such as anxiety, dizziness, head-headed feeling and headache, and neurological deficits (N). Each factor was graded and scored. Statistically, there was a significant correlation between thalamic rCBF (Y) and mean CBF (X) in the less affected hemisphere: Y = 1.82X + 2.2, r = 0.801, p < 0.001, n = 65. Multiple regression analysis of the thalamic rCBF revealed that the Sz factor was significant (p < 0.0001) on the lesion side: Y = 76.7-10.2Sz, r = 0.644, p < 0.001, n = 51, while the Se, Sd and St factors were significant (p < 0.005) on the less affected side: Y = 71.9 + 9.7Se-6.8Sd-5.0St, R = 0.585, p < 0.001, n = 65. The thalamic index (X), an indicator of thalamic atrophy, and thalamic rCBF were significantly correlated: Y = 28.7X + 10.2, r = 0.386, p < 0.001, n = 80. In conclusion, thalamic rCBF appeared to reflect the degree of organic changes and time course in the cerebral hemisphere, because factors such as size, sex and stage were statistically significant.     

Altered response to histamine in brain tumor vessels: the selective increase of regional cerebral blood flow in transplanted rat brain tumor

The authors studied the effect of intracarotid administration of histamine on the regional cerebral blood flow (rCBF) in transplanted rat C6 glioma by the hydrogen clearance method. Histamine infusion at doses of 1 and 10 micrograms/kg/min produced an increase of rCBF in the tumor (24.6% +/- 16.4%, p < 0.002, and 37.6% +/- 18.2%, p < 0.0001, respectively) and also in brain surrounding the tumor (26.8% +/- 16.2%, p < 0.002, and 34.9% +/- 9.2%, p < 0.0001, respectively) without any significant changes in the ipsilateral hemisphere. Intravenous administration of pyrilamine (H1 antagonist) and cimetidine (H2 antagonist) reduced blood flow responses to histamine; cimetidine was a more effective blocking agent than pyrilamine. Intracarotid infusion of histamine (1 and 10 micrograms/kg/min) with intravenous injection of Evans blue dye disclosed the selective extravasation of dye in the tumor and the brain surrounding the tumor. These results indicated that brain tumor vessels could respond to histamine differently than normal brain capillaries. The mechanism of selective response to histamine could be explained either by increased permeability or by altered characteristics of histamine receptors in the tumor vessels.     

Pathological regional cerebral blood flow in opiate-dependent patients during withdrawal: a HMPAO-SPECT study

Diabetic retinopathy is one of the most important causes of blindness. Diabetic patients do not attend outpatient clinics with the necessary regularity for an early diagnosis of the most severe forms of retinopathy. A program was planned to compare the efficiency of a 45 degrees non-mydriatic retinal camera with a Polaroid instant film versus biomicroscopy with a 78D lens and reverse image ophthalmoscope (standard method) in the diagnosis of the presence and evolutive degree of retinopathy. In a cross-sectional epidemiologic study a questionnaire was administered to 258 randomly selected diabetic patients, 129 with and 128 without retinopathy. Information was collected of demographics, visual acuity, diabetes and resources used with each method. The eye fundus with the poorest visual acuity was examined to determine the presence and evolution of retinopathy with the two diagnostic methods. The photographic method had an overall sensitivity of 91.1%, a specificity of 89.7% and a level of agreement of 82% with the standard method. A cost-effective analysis revealed a decrease of 35.7% in the cost per true positive case detected with the photographic methods versus the standard method. The 45 degrees non-mydriatic retinal camera had a similar efficiency to the standard method used in our setting for the diagnosis of diabetic retinopathy, which together with a lower cost per patient renders this method advisable for its use in medical settings that usually control for potential ophthalmologic complications resulting from diabetes mellitus.     

Regional cerebral blood flow during and after 2 hours of middle cerebral artery occlusion in the rat

In this study we explored if the secondary bioenergetic failure, which occurs a few hours after recirculation, following transient middle cerebral artery occlusion (MCAO) in rats, is caused by a compromised reflow. We induced 2 hours of MCAO and measured CBF at the end of the ischemia, as well as 15 minutes, 1, 2, and 4 hours after the start of recirculation, using autoradiographic or tissue sampling 14C-iodoantipyrine techniques. After 2 hours of MCAO, the autoradiographically measured CBF in the ischemic core areas was reduced to 3 to 5% of contralateral values. The reduction in CBF was less in neighboring, penumbral areas. After recirculation, flow already normalized in core tissues after 15 minutes, and remained close to normal for the 4 hours recirculation period studied. However, in penumbral tissues, recovery CBF values were usually below normal. The results show that tissues that are heavily compromised by the 2-hour period of ischemia and are destined to incur infarction, show a "relative hyperemia" during recirculation. In fact, some areas of the previously densely ischemic tissue showed overt hyperperfusion. This finding raises the question whether the relative or absolute hyperemia reflects events that are pathogenetically important. Because drugs that clearly ameliorate the final damage incurred fail to alter the relative hyperperfusion of previously ischemic tissues, it is concluded that vascular events in the reperfusion period do not play a major role in causing the final damage.     

Correlation between regional cerebral blood flow and oxidative metabolism. In vivo studies in man

To test the hypothesis that regional cerebral blood flow (rCBF) is normally regulated by regional metabolic activity, rCBF and the regional cerebral metabolic rate for oxygen (rCMRO2) were compared in selected human subjects. In normal subjects and patients with chronic, stable diseases of brain, rCBF correlated well with rCMRO2. In one individual with mild dementia, rCBF and rCMRO2 were measured before and during exercise of the hand and forearm contralateral to the hemisphere studied. Appropriate parallel changes occurred in both rCBF and rCMRO2 during hand exercise. In patients with acute diseases affecting the hemisphere studied, however, the correlation between rCBF and rCMRO2 was unpredictable.     

Effects of syntactic structure and propositional number on patterns of regional cerebral blood flow

BACKGROUND: Intravascular catheters are associated with severe infections in patients, but only few reports on this problem in animal research exist. OBJECTIVE: We report on catheter-related bacterial colonization and its consequences in long-term catheterized animals. MATERIAL AND METHOD: Foxhounds were instrumented with intravascular catheters and flow probes to study the regulation of renal blood flow and pressures. RESULTS: After flushing the catheters, alterations in renal blood flow were observed and these could be related to bacterial colonization of intravascular catheters with Pseudomonas species. After attention had been focused on aseptic technique in all experimental phases and prophylactic antibiotic lock instituted, the occurrence of Pseudomonas bacteremia ceased, and the magnitude and incidence of catheter-related colonization and infection by Pseudomonas species dropped considerably. CONCLUSION: The catheter-related colonization that occurred spontaneously in these animals resembled findings in animal experiments in which catheter-related infections were deliberately induced as well as observations made with regard to catheter-related infections in patients. This report emphasizes the importance of asepsis when working with animals with long-term intravascular catheters. We suggest that monitoring for this complication, e.g., by means of catheter cultures at the time of removal, should routinely be part of protocols for animal experiments using long-term intravascular catheters.     

The trigeminal nerve and augmentation of regional cerebral blood flow during experimental bacterial meningitis

We investigated whether trigeminal nerve fibers contribute to enhanced regional cerebral blood flow (rCBF) in a rat model of experimental bacterial meningitis. rCBF was measured continuously for 6 h by laser Doppler flowmetry through thinned bone over the frontal cortex. Meningitis was induced with pneumococcal cell wall components and confirmed by a significant increase of (a) leukocytes within the cerebrospinal fluid, (b) brain water content, (c) intracranial pressure and (d) rCBF. The increase of rCBF was significantly attenuated (p < 0.05) at 3, 4, 5, and 6 h in animals after a chronic (200 +/- 21% versus 138 +/- 13% at 6 h on the intact and denervated sides, respectively) but not after an acute section of the nasociliary branch of the trigeminal nerve. We conclude that elevations in blood flow during the early phase of bacterial meningitis are mediated in part by the trigeminal nerve, probably by local perivascular release of neuropeptides from afferent axons innervating the meninges.