Alterations In Cerebral Perfusion Research Articles

Altered cerebral perfusion measured by SPECT in relatives of patients with schizophrenia. Correlations with memory and P300.

Genetic studies in schizophrenia are hampered by the complex heterogeneous clinical phenotype. Biological variables identified as trait markers of risk could clarify the mode of inheritance, define clinical subgroups and provide clues about aetiology. To use single photon emission computed tomography (SPECT) to compare brain perfusion maps in patients with schizophrenia (n = 19), their asymptomatic 'high-risk' relatives (n = 36) and control subjects (n = 34) and to examine the relationships between imaging, memory and P300 event-related potential. SPECT, memory tests and P300 recording were carried out. In the patients with schizophrenia and their relatives, perfusion was reduced in left inferior prefrontal and anterior cingulate cortex and increased bilaterally in a subcortical region. Perfusion significantly correlated with verbal memory and P300 amplitude in left inferior prefrontal cortex and with P300 latency in anterior cingulate cortex. Medication- and symptom-free relatives had altered regional perfusion intermediate between subjects with schizophrenia and controls. Impaired perfusion, verbal memory and P300 appear to be related traits associated with an increased risk of illness.

Deregulation of cyclooxygenase and nitric oxide synthase gene expression in the inflammatory cascade triggered by experimental group B streptococcal meningitis in the newborn brain and cerebral microvessels

Group B Streptococcus (GBS) is the most common cause of neonatal sepsis and meningitis. Despite antibiotics, GBS in the newborn initiates a cascade of molecular and biological events leading to altered cerebral perfusion, blood-brain barrier disruption, cerebral edema, intracranial hypertension, neurological damage, and even death. Having previously shown that GBS infection impairs cerebral blood flow autoregulation and increases prostaglandin (PG) levels, we examined the regulation of some crucial inflammatory mediators (PGs, nitric oxide (NO), tumor necrosis factor-a) in the brain and cerebral microvessels (MVs) from newborn piglets. Cyclooxygenase (COX), the key enzyme in PG biosynthesis, exists in two isoforms, COX-1 and COX-2. Both may be directly induced by NO in a model of renal inflammation. Besides its neurotransmitter role, NO is a potent vasorelaxant whose production is catalyzed by at least three distinct nitric oxide synthases (NOS) (bNOS, ecNOS, iNOS). Western blot analyses showed that the newborn (4 day old) brain expressed lower levels of COX-1 (8-fold), COX-2 (20-fold), bNOS (12-fold), and ecNOS (5-fold) than in the 1 day old. MV showed approximately equal levels of COX-2, lower levels of COX-1 (4-fold), bNOS (5-fold), and higher levels of ecNOS (20-fold) in comparison to 4-day-old cerebral MV. A 4-day-old brain expressed lower levels of bNOS (5-fold), ecNOS (10-fold), and COX-1 (2-fold) than the 6-week-old pig. COX-2 protein was undetected in a 4-day-old pig brain, but present in great excess in MV. Purified MV showed lower ecNOS (14-fold), COX-1 (2-fold), and about equal levels of bNOS and COX-2 in comparison with MV from 6-week-old pigs. Reverse transcription polymerase chain reaction analyses confirmed these results. Treatment with noo-nitro-L-arginine (LNA), a NOS inhibitor, downregulated COX-1 expression in the newborn brain and both COX-1 and COX-2 cerebral MV expression. GBS infection (10(9) colony-forming units, 0.5 mL intracerebroventricular) of sedated newborn piglets induced the expression of tumor necrosis factor-alpha in the cerebrospinal fluid after 2 hours, upregulated bNOS expression in both brain and MVs, upregulated ecNOS in MVs, and downregulated COX-1, COX-2, and ecNOS in the brain. GBS did not trigger the expression of iNOS. Our data suggest that there is a net deficiency of NOS isoforms in the immature brain and microvasculature of the 4-day-old piglet and that the differences in expression lead to the immature control of NO and PG production, rendering newborns particularly susceptible to neurological damage because of the undeveloped nature of their response mechanisms. Moreover, the GBS-induced cascade deregulates the gene expression of interacting inflammatory mediators and may cause a net vasoconstrictor/vasodilator imbalance, leading to cerebral hypertension and edema in the early stages of infection. Pharmacological manipulations of the inflammatory cascade could lead to novel therapeutic approaches for the treatment of GBS meningitis.

Analysis of heart-rate variability: a noninvasive predictor of death and poor outcome in patients with severe head injury.

Analysis of heart-rate variability (HRV) is a promising new technique for noninvasive quantification of autonomic function. We measured HRV in patients with severe head injury to assess its potential as a monitoring tool. Analysis of HRV was prospectively done on all intensive care unit patients. Concurrent data on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were collected. Registry data were reviewed to identify patients with severe head injury, defined as Head/Neck Abbreviated Injury Scale score > or = 4. Mortality, likelihood of discharge to home, ICP, and CPP were compared between patients with abnormal HRV and those without. Low HRV was associated with increased mortality and decreased rate of discharge to home. Abnormal HRV was associated with episodes of increased ICP and decreased CPP. Assessment of HRV is a noninvasive method that can be widely used. Abnormal HRV was associated with poor outcome and altered cerebral perfusion. Monitoring of HRV may improve outcome by allowing earlier detection and treatment of intracranial pathology.

Cerebral blood flow correlates of apathy in Alzheimer disease.

Apathy is a pervasive noncognitive neuropsychiatric disturbance in Alzheimer disease, which causes significant caregiver distress. The neuroanatomical substrate of apathy is not well understood. To study the relationship between regional cerebral blood flow and the presence and severity of the personality disturbance, apathy, in individuals with Alzheimer disease. Analysis of the relationship between regional cerebral blood flow as measured by single photon emission computed tomography and severity of apathy as measured by the Neuropsychiatric Inventory using an analysis of variance design. We examined regional cerebral perfusion alterations as measured by xenon 133Xecalibrated technetium Tc 99m hexamethyl-propyleneamine-oxime single photon emission computed tomography in relation to the presence and severity of apathy. The neurology clinics of the University of California, Los Angeles, UCLA School of Medicine, and Harbor-UCLA Medical Center. Thirty-one community-dwelling patients fulfilling National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association diagnostic criteria for probable Alzheimer disease who had a single photon computed tomographic scan performed within 3 months of administration of the Neuropsychiatric Inventory. The presence of apathy was associated with more severe prefrontal and anterior temporal dysfunction. These regional cerebral perfusion relationships with apathy were independent of cognitive decline except in the dorsolateral prefrontal cortex. These results demonstrate the association of apathetic syndromes with prefrontal and anterior temporal regional brain dysfunction and are consistent with similar findings previously reported in other disorders.

Cardiopulmonary bypass, myocardial management, and support techniques Changes in autonomic response of the cerebral circulation after normothermic extracorporeal circulation

Patients who undergo cardiopulmonary bypass frequently have neuropsychologic dysfunction. This study was undertaken to determine whether altered cerebral perfusion and vascular responses may in part lead to these neuropsychologic changes. Pigs were placed on normothermic cardiopulmonary bypass for 2 hours. Basal cerebral blood flow and in vivo responses to administration by internal carotid artery of neuronally released vasoactive substances were evaluated before and 5 to 15 minutes after termination of cardiopulmonary bypass. Another group of pigs were placed on cardiopulmonary bypass for 2 hours and then perfused off bypass for 1 additional hour. In vitro responses of cerebral arterial microvessels (100 to 175 μm) from both groups were examined in a pressurized (40 mm Hg) no-flow state with videomicroscopy. Vessels from uninstrumented pigs served as control preparations for in vitro studies. Cerebrovascular resistance and cerebral perfusion were maintained constant during cardiopulmonary bypass and after separation from bypass. The internal carotid artery infusion of acetylcholine (cholinergic agonist) caused increased internal carotid artery blood flow before cardiopulmonary bypass but decreased blood flow after cardiopulmonary bypass. After 2 hours of cardiopulmonary bypass, the increase in internal carotid artery blood flow induced by isoproterenol (a β-adrenoceptor agonist) was reduced, whereas the response to sodium nitroprusside (a guanylate cyclase activator) was unchanged. In vitro acetylcholine-induced microvascular vasodilation was converted to a contractile response and isoproterenol elicited less relaxation after 2 hours of cardiopulmonary bypass. One hour of cerebral perfusion after cardiopulmonary bypass caused a further reduction in isoproterenol-induced relaxation but had no further effect on the cholinergically mediated response. In vitro relaxation responses to sodium nitroprusside and forskolin (an adenylate cyclase activator) were similar in all experimental groups, suggesting that second-messenger mechanisms remain intact after normothermic cardiopulmonary bypass. In conclusion, basal cerebrovascular resistance and internal carotid artery blood flow are maintained if the systemic circulation and pressure are supported with fluid administration after cardiopulmonary bypass. Agonist-induced vasodilation of cerebral microvessels to cholinergic and β-adrenoceptor stimulation are selectively impaired after normothermic cardiopulmonary bypass, whereas second-messenger mechanisms remain intact. (J T horac C ardiovasc S urg 1996;112:450-61)

A study of cerebral perfusion using single photon emission computed tomography in neonates with brain lesions.

In this study we used a single photon emission computed tomography technique (SPECT) with radiolabelled 99mTcHMPAO to assess cerebral perfusion in newborn infants with documented cerebral lesions and to determine to what extent brain SPECT might be useful in the neonatal period. A total of 15 newborn infants with the following cerebral pathologies were enrolled: severe parietal bilateral periventricular leucomalacia (PVL, n = 6); moderate parietal bilateral PVL (n = 2); intraventricular haemorrhage grade II with unilateral parietal parenchymal extension (IHV + PE, n = 3); cerebral infarction (CI, n = 2) in the zone of middle cerebral artery; and post-haemorrhagic hydrocephalus (n = 2). Follow-up was available in all infants. Alterations in cerebral perfusion were seen in only 12 of 15 infants and at the location of severe PVL, PE and CI. We have noted that the regions of diminished perfusion extended beyond the apparent extent of cerebral pathology delineated by ultrasound or magnetic resonance imaging. Markedly diminished perfusion was seen in 1 infant with hydrocephalus, which recovered following placement of ventriculo-peritoneal shunt. Regarding outcome, SPECT data failed to provide additional information than that of neuroradiological investigations. We conclude that the use of SPECT, under these conditions, to assess alteration of cerebral perfusion in the neonatal period will not provide any additional information than that of neuroradiological investigations.

Hippocampal damage in fatal paediatric head injury.

The hippocampus is known to be frequently involved in head injury. In adults, such hippocampal lesions frequently include regions of selective neuronal necrosis. The present report examines the frequency and distribution of hippocampal damage in 37 cases of fatal head injury in children. Damage to the hippocampus was noted in 27 of 37 cases (73%). Lesions were often focal areas of selective neuronal necrosis located in the CA-1 subfield. Other subfields of the hippocampus were involved to lesser degrees. The frequency and distribution of hippocampal damage in fatal childhood head injury is similar to that reported for fatal head injuries of all ages. Pathological evidence of high intracranial pressure and/or hypoxic brain damage in other anatomical locations was present in the majority of cases. Clinical seizures prior to death occurred in 22% of the cases studied. However, these factors could not account for all cases of hippocampal damage in the present report. Thus, the hippocampus is frequently damaged in fatal head injury in children. The mechanisms involved in the production of such damage may involve hypoxia, raised intracranial pressure and altered cerebral perfusion. However, other, yet to be elucidated, mechanisms may be involved.

Ultrafast MR imaging of water mobility: animal models of altered cerebral perfusion.

"Single shot" magnetic resonance (MR) diffusion imaging was used to study the details of signal decay curves in experimental perturbations of cerebral perfusion induced by hypercapnia or death. Despite large perfusion increases observed with dynamic susceptibility-contrast MR imaging, no correlation with these changes was seen in either the diffusion coefficient or any other intravoxel incoherent motion (IVIM) model parameters in dog gray matter as arterial carbon dioxide pressure increased. Non-monoexponential signal decay in cat gray matter was seen both before and after death. In addition, cat gray matter demonstrated a steady decrease in the diffusion coefficient after death. These data are strong evidence that the fast component of the non-monoexponential diffusion-related signal decay is not due solely to perfusion. The authors believe that a second compartment of nonexchanging spins, most likely cerebrospinal fluid, accounts for the non-monoexponential decay.

A comparison of transcranial doppler ultrasound (TCD) and radioactive microspheres in determining cerebral perfusion in normal and low flow states

We have previously utilized the technique of transcranial Doppler (TCD) ultrasound to determine cerebral perfusion in patients undergoing cardiopulmonary resuscitation (CPR). In order to assess if TCD can reliably measure alterations in cerebral perfusion under conditions of normal and low cardiac outputs, we compared TCD measured blood flow velocities in the middle cerebral artery (MCA) of six piglets with radioactive microsphere determinations of total cerebral perfusion at baseline normal sinus rhythm (NSR), during CPR, and following return of spontaneous circulation (ROSC). Peak systolic and mean blood flow velocities were compared to the microsphere perfusion results on 15 different occasions; six during NSR, five during CPR, and four following ROSC. Although qualitative alterations in TCD measurements reflected changes in microsphere perfusion, we could not find a statistically significant correlation between either peak systolic or mean MCA blood flow velocities and microsphere perfusion measurements either overall or in any subgroup. The possible reasons which may explain the findings are discussed.

Cerebral abnormalities in cocaine abusers: demonstration by SPECT perfusion brain scintigraphy. Work in progress.

Single photon emission computed tomography (SPECT) perfusion brain scans with iodine-123 isopropyl iodoamphetamine (IMP) were obtained in 12 subjects who acknowledged using cocaine on a sporadic to a daily basis. The route of cocaine administration varied from nasal to intravenous. Concurrent abuse of other drugs was also reported. None of the patients were positive for human immunodeficiency virus. Brain scans demonstrated focal defects in 11 subjects, including seven who were asymptomatic, and no abnormality in one. Among the findings were scattered focal cortical deficits, which were seen in several patients and which ranged in severity from small and few to multiple and large, with a special predilection for the frontal and temporal lobes. No perfusion deficits were seen on I-123 SPECT images in five healthy volunteers. Focal alterations in cerebral perfusion are seen commonly in asymptomatic drug users, and these focal deficits are readily depicted by I-123 IMP SPECT.

Mannitol treatment in experimental haemophilus influenzae type b meningitis

ABSTRACT. A study was undertaken to evaluate hypertonic mannitol treatment in experimental lapin Haemophilus influenzae type b meningitis and to compare these results with those in normal rabbits. Increased intracranial pressure, brain water content, and concentrations of lactate and hypoxanthine in cerebrospinal fluid (CSF) were measured as a reflection of altered cerebral perfusion and hypoxia and potential brain injury associated with meningitis. A single dose of mannitol reduced transiently the CSF pressure of uninfected rabbits from 2.15 ± 0.20 to 1.34 ± 0.10 mm Hg (maximum reduction 34.9 ± 8.4%; p 0.05). CSF lactate and hypoxanthine concentrations were significantly increased during the 20 h of meningeal inflammation (p < 0.005). The mean percentage change from baseline values for lactate concentrations at the end of the experiment (24 h) in infected mannitol-treated rabbits was significantly smaller than that in infected untreated animals (p = 0.035). A single dose of mannitol reduced the CSF hypoxanthine concentrations of infected animals, but this reduction was not statistically significant.

Evaluation of regional cerebral circulation based on absolute mean transit times in radionuclide cerebral angiography

In radionuclide cerebral angiography (RCA) the analysis of the activity-time curves recorded over the hemispheres following an intravenous bolus injection of a radioactive indicator permits the evaluation of absolute cerebral mean transit times (MTTcb). The inverse of MTTcb is an index of cerebral blood flow. The bolus parts of the cerebral activity curves were fitted with gamma-variate functions. The duration of the injection bolus and its subsequent dispersion through the cardiopulmonary circulation were corrected for using the activity curve over the aortic arch. The RCA is non-invasive, rapid, easy to perform and without risk for the patient. The RCA is recommended for quantitative evaluation of major alterations in cerebral perfusion.

Mannitol Treatment in Experimental Haemophilus influenzae Type b Meningitis

A study was undertaken to evaluate hypertonic mannitol treatment in experimental lapin Haemophilus influenzae type b meningitis and to compare these results with those in normal rabbits. Increased intracranial pressure, brain water content, and concentrations of lactate and hypoxanthine in cerebrospinal fluid (CSF) were measured as a reflection of altered cerebral perfusion and hypoxia and potential brain injury associated with meningitis. A single dose of mannitol reduced transiently the CSF pressure of uninfected rabbits from 2.15 +/- 0.20 to 1.34 +/- 0.10 mm Hg (maximum reduction 34.9 +/- 8.4%; p less than 0.005). The time to the lowest pressure was 38.7 +/- 2.7 min after initiation of the infusion and the time to return of CSF pressure to initial values was 76.7 +/- 5.6 min. In infected mannitol-treated animals the CSF pressure was reduced from 4.78 +/- 0.53 to 2.61 +/- 0.55 mm Hg (maximum reduction 42.0 +/- 7.7%; p less than 0.005). Time to maximum pressure decrease was 44.0 +/- 5.6 min. CSF pressure returned to the initial level after 178.5 +/- 25.2 min. Four h after initiation of mannitol infusion the mean brain water content in infected mannitol-treated animals was 412 +/- 4 g H2O/100 g dry weight and in infected untreated animals it was 415 +/- 3 g H2O/100 g dry weight (p greater than 0.05). CSF lactate and hypoxanthine concentrations were significantly increased during the 20 h of meningeal inflammation (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of acute carbon monoxide intoxication on the cerebral energy metabolism of the rat.

The cerebal metabolic effects of 60 min exposure to 0.5, 1.0, 1.5, and 2.0% carbon monoxide (CO) and 60 min exposure to 1.0% CO were studied in lightly anesthetized rats by measurement of brain tissue contents of glycolytic and citric acid cycle intermediates, as well as tissue energy phosphates. The results indicate that cerebral energy homeostasis is maintained until advanced levels of CO intoxication (2.0%) are reached. Animals exposed to 2.0% CO developed significant decreases in systemic blood pressure, with attendent decreases in cerebral ATP, increases in ADP and AMP, plus early depletions of tissue citrate and alpha-oxyglutarate. The similarity of this pattern to that previously documented for various cerebral oligemic states suggests a possible modifying role for altered cerebral production in its production. A correlation between conscious behavior and cerebral energy state was suggested by the observation that unanesthetized animals exposed to 1.0% CO for 30 and 60 min retained consciousness, whereas animals exposed to 2.0% CO for 30 min became unresponsive late on in the exposure. A comparison of CO induced changes in intermediary metabolites, energy phosphates, intracellular pH, and cytoplasmic redox state with those seen in hypoxemia indicate no basic qualitative or quantiative differences in the metabolic response of brain tissue to the two conditions.