Diffusion-weighted magnetic resonance imaging in a case of cerebral venous thrombosis

BACKGROUND: Diffusion-weighted imaging (DWI) is the most sensitive MR sequence in acute arterial ischemic stroke but has not yet been evaluated in venous cerebral ischemia. We describe a patient with DWI performed at the acute phase of a venous ischemic stroke. CASE DESCRIPTION: A rapid cerebral MRI including DWI and fast fluid-attenuated inversion recovery (FLAIR) sequences was performed at the acute phase of a venous stroke confirmed by conventional angiography. DWI showed a slight decrease in apparent diffusion coefficient values 3 hours after onset (0.53+/-0.07x10(-3) mm2/s) and was normal 48 hours later (0.064+/-0.15x10(-3) mm2/s). Fast FLAIR sequences showed large left frontoparietal hyperintensities. The lack of a clear decrease in apparent diffusion coefficient values associated with marked FLAIR abnormalities may suggest prominent or early associated vasogenic edema. Physiopathological differences between arterial and venous ischemia may explain the different type of DWI FLAIR abnormalities during the acute phase as well as the better recovery of neurological deficit in venous stroke than in arterial ischemic stroke. CONCLUSIONS: In the context of an acute stroke, the contrast between marked FLAIR and subtle DWI abnormalities on MRI may reflect the venous mechanism of cerebral ischemia.     

A positive crossmatch in liver transplantation--no effect or inappropriate analysis? A prospective study

Secondary brain damage after transient cerebral hypoxia-ischemia (HI) is caused by a cascade of cellular events. In this study, complementary methods of magnetic resonance imaging and histochemistry were used to investigate the formation of cytotoxic and vasogenic edema during secondary brain damage induced by transient HI in 7-d-old rats. To elicit injury, 21 rats underwent right common carotid artery ligation followed by 1.5 h of 8% O2 exposure. Sequential apparent diffusion coefficient (ADC) and transversal relaxation time (T2) weighted magnetic resonance imaging were recorded for up to 3 d in 13 7-d-old rats. Eight animals were killed at various intervals between the end of HI and 21 h of recovery to perform histochemical assays using neuronal and astrocytic markers. Changes of the ADC revealed a biphasic function for the evolution of cytotoxic edema during the recovery period. At the end of HI, the ADC in the ipsilateral cortex was significantly decreased. Upon reoxygenation, it returned transiently to normal followed by a secondary, although less pronounced, decline after 8-48 h. After this, the ADC rose steadily. From 8 h of recovery, the proportion of vasogenic edema steadily increased as indicated by the T2 prolongation. At 21 h, the majority of glial cells showed immunoreactivity for glial fibrillary acidic protein and were of larger size, whereas the neurons were apoptotic. These results indicate that the delayed cerebral injury is accompanied by late glial swelling in conjunction with an enlarged interstitial space due to cell damage.     

Differential distribution of striatal [123I]beta-CIT in Parkinson's disease and progressive supranuclear palsy, evaluated with single-photon emission tomography

Functional imaging of the presynaptic dopaminergic activity using single-photon emission tomography (SPET) and iodine-123 labelled 2-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane ([123I]beta-CIT) is important for the assessment of disease severity and progression in patients with Parkinson's disease (PD). However, its capability to discriminate between different extrapyramidal disorders has not yet been assessed. The aim of this study was to evaluate the possibility of differentiating patients with PD and with progressive supranuclear palsy (PSP) by means of this method. The distribution of [123I]beta-CIT in the basal ganglia was assessed in six normal subjects, 13 petients with PD and five patients with PSP in whom the disease was mild. SPET images were obtained 24+/-2 h after i.v. injection of the tracer using a brain-dedicated system (CERASPECT). MR and SPET images were co-registered in four normal subjects and used to define a standard set of 16 circular regions of interest (ROIs) on the slice showing the highest striatal activity. The basal ganglia ROIs corresponded to (1) the head of caudate, (2) a region of transition between the head of caudate and the anterior putamen, (3) the anterior putamen and (4) the posterior putamen. A ratio of specific to non-displaceable striatal uptake was calculated normalising the activity of the basal ganglia ROIs to that of the occipital cortex (V3"). ANOVA revealed a global reduction of V3" in all ROIs of PD and PSP patients compared with normal controls (P<0. 0001). A Mann-Whitney U test showed that the difference between PD and PSP patients was statistically significant for the caudate region only (Z value: 2.6; P<0.01). By subtracting V3" caudate values from those of the putamen, differentiation from PSP was possible in 10/13 PD patients. In conclusion, analysis of [123I]beta-CIT distribution in discrete striatal areas provides information on the relative caudate-putamen damage, with different values being obtained in patients clinically diagnosed as having either PD or PSP.     

PET studies on brain monoamine transporters with carbon-11-beta-CIT in Parkinson's disease

The cocaine analog 2 beta-carbomethoxy-3 beta-[4-iodophenyl]tropane (beta-CIT) labeled with 11C was used to study dopamine reuptake sites with PET. METHODS: Three normal subjects and nine patients with Parkinson's disease were investigated. Each of them underwent a dynamic PET scan (25 timeframes over 80 min) with [11C]-beta-CIT. A dose of 102.5-211.3 MBq (2.77-5.71 mCi) of this ligand was administered intravenously and a PET examination with an ECAT 931/08 PET camera was carried out. Ratios between the striatal/cortical/thalamic/midbrain and cerebellar uptake of this radioligand were calculated. RESULTS: The highest accumulation of [11C]beta-CIT was observed in the caudate and putamen, though there was some uptake in the thalamus and the midbrain. Cortical uptake was negligible. Carbon-11-beta-CIT accumulated significantly less in the putamen of the Parkinson's patients than in the normal subjects. The putamen-to-cerebellum ratio in the Parkinson's patients was 1.59 +/- 0.04 and 1.80 +/- 0.13s (p = 0.028) in the normal subjects. In the caudate, there was no significant difference between the Parkinson's patients and the normal subjects. CONCLUSION: These results imply that [11C]beta-CIT is a useful compound for carrying out a PET examination of the function of the presynaptic monoaminergic neurons both in normal and pathological brains.     

Temporal and anatomical variations of brain water apparent diffusion coefficient in perinatal cerebral hypoxic-ischemic injury: relationships to cerebral energy metabolism

Cerebral apparent diffusion coefficients (ADCs) were determined in nine newborn piglets before and for 48 h after transient hypoxia-ischemia. Phosphorus MRS revealed severely reduced cerebral energy metabolism during the insult and an apparently complete recovery 2 h after resuscitation commenced. At this time, mean ADC over the imaging slice (ADCglobal) was 0.88 (0.04) x 10(-9) m2 x s(-1) (mean (SD)), which was close to the baseline value of 0.92 (0.4) x 10(-9) m2 x s(-1). In seven of the animals, a "secondary" failure of energy metabolism then evolved, accompanied by a decline in ADCglobal to 0.64 (0.17) x 10(-9) m2 x s(-1) at 46 h postresuscitation (P < 0.001 versus baseline). For these seven animals, ADCglobal correlated linearly with the concentration ratio [phosphocreatine (PCr)]/[inorganic phosphate (Pi)] (0.94 < r < 0.99; P < 0.001). A nonlinear relationship was demonstrated between ADCglobal and the concentration ratio [nucleotide triphosphate (NTP)]/[Pi + PCr + 3 NTP]. The ADC reduction commenced in the parasagittal cortex before spreading in a characteristic pattern throughout the brain. ADC seems to be closely related to cerebral energy status and shows considerable potential for the assessment of hypoxic-ischemic injury in the newborn brain.     

Crystal structure of GCN4-pIQI, a trimeric coiled coil with buried polar residues

BACKGROUND AND PURPOSE: Early and accurate diagnosis of brain edema in stroke patients is essential for the selection of appropriate treatment. We examined the correlations between the changes in the apparent diffusion coefficient (ADC), regional water content, and tissue ultrastructure during early focal cerebral ischemia. METHODS: The left middle cerebral arteries of cats were occluded with an intramagnet occlusion/recirculation device. T2-weighted, diffusion-weighted, and perfusion imaging were performed repeatedly during the initial 3 hours after occlusion. The ADCs obtained from ADC maps were compared with the corresponding tissue water content values determined by gravimetry and electron microscopic water localization. RESULTS: ADC reduction was detected in areas of low perfusion 15 minutes after occlusion and thereafter. The water content increase correlated linearly with the ADC decreases in both the gray and white matter. However, both the water content corresponding to an ADC value and the rate of ADC change of the gray and white matter differed significantly (P<.05) as follows: y = -10105x + 8533 (r=.86) and y = -6174x + 4611 (r=.67), respectively, where x is the water content (grams water per gram tissue) and y is the ADC (x 10(-6) mm2/s). Hydropic astrocytic swelling was seen in both structures, and in the white matter, oligodendroglial and myelinated axonal swelling and periaxonal space enlargement were observed. CONCLUSIONS: When early ischemic edema in experimental focal cerebral ischemia is evaluated with ADC mapping, the different slopes and intercepts of the water content and ADC correlation lines for the gray and white matter, which probably reflect different ultrastructural localization of water, should be taken into account.     

Characterization of cerebral hemodynamic phases following severe head trauma: hypoperfusion, hyperemia, and vasospasm

The extent and timing of posttraumatic cerebral hemodynamic disturbances have significant implications for the monitoring and treatment of patients with head injury. This prospective study of cerebral blood flow (CBF) (measured using 133Xe clearance) and transcranial Doppler (TCD) measurements in 125 patients with severe head trauma has defined three distinct hemodynamic phases during the first 2 weeks after injury. The phases are further characterized by measurements of cerebral arteriovenous oxygen difference (AVDO[2]) and cerebral metabolic rate of oxygen (CMRO[2]). Phase I (hypoperfusion phase) occurs on the day of injury (Day 0) and is defined by a low CBF calculated from cerebral clearance curves integrated to 15 minutes (mean CBF 32.3 +/- 2 ml/100 g/minute), normal middle cerebral artery (MCA) velocity (mean V[MCA] 56.7 +/- 2.9 cm/second), normal hemispheric index ([HI], mean HI 1.67 +/- 0.11), and normal AVDO(2) (mean AVDO[2] 5.4 +/- 0.5 vol%). The CMRO, is approximately 50% of normal (mean CMRO(2) 1.77 +/- 0.18 ml/100 g/minute) during this phase and remains depressed during the second and third phases. In Phase II (hyperemia phase, Days 1-3), CBF increases (46.8 +/- 3 ml/100 g/minute), AVDO(2) falls (3.8 +/- 0.1 vol%), V(MCA) rises (86 +/- 3.7 cm/second), and the HI remains less than 3 (2.41 +/- 0.1). In Phase III (vasospasm phase, Days 4-15), there is a fall in CBF (35.7 +/- 3.8 ml/100 g/minute), a further increase in V(MCA) (96.7 +/- 6.3 cm/second), and a pronounced rise in the HI (2.87 +/- 0.22). This is the first study in which CBF, metabolic, and TCD measurements are combined to define the characteristics and time courses of, and to suggest etiological factors for, the distinct cerebral hemodynamic phases that occur after severe craniocerebral trauma. This research is consistent with and builds on the findings of previous investigations and may provide a useful temporal framework for the organization of existing knowledge regarding posttraumatic cerebrovascular and metabolic pathophysiology.     

Spreading waves of a reduced diffusion coefficient of water in normal and ischemic rat brain

Using echo planar diffusion-weighted magnetic resonance imaging, we measured three-dimensional changes in the apparent diffusion coefficient (ADC) of water in eight contiguous coronal slices, encompassing the entire rat brain, before and after local cortical stimulation. We applied chemical (potassium chloride application; n = 6) and mechanical (needle stab; n = 4) stimulations to the right posterior parietal rat cortex. In all animals in which potassium chloride or the needle stab was applied, a region of decreased ADC values to a mean of 0.45 +/- 0.03 x 10(-5)cm2/s occurred. These reduced ADC levels appeared in the posterior parietal cortex within 1 min after cortical stimulation and the change recovered within 1 min. Then a ripple-like movement of similar changes developed across the unilateral cortex. This change was localized to the cortex and no significant ADC changes occurred in subcortical structures. The propagating speed of this movement was 3.4 +/- 0.5 mm/min. These findings are compatible with spreading depression as observed electrophysiologically. Similar ADC changes occurred in areas distinct from the ischemic lesion in 3 of 12 animals subjected to focal cerebral ischemia. This magnetic resonance method could detect spreading ADC decline if it occurred in human diseases including brain ischemia.     

Opioid receptors on peripheral sensory axons

Enzyme-modified amperometric microsensors have been utilized in the investigation of acetylcholine and choline diffusion in solution and choline uptake and diffusion in rat brains. A small amount of the substance of interest was introduced by pressure injection and transport to the sensor was monitored. The apparent diffusion coefficients for acetylcholine and choline in agarose gel perfused with physiological solutions were determined to be 5.2 +/- 0.7 x 10(-6) cm2/s and 6.1 +/- 0.8 x 10(-6) cm2/s, respectively. Choline transport was monitored in two brain regions: the caudate and anterior hypothalamus. The transport time of choline in the caudate was concentration dependent, but was unaffected by the presence of a competitive, high-affinity uptake inhibitor, hemicholinium-3. The apparent diffusion coefficient (D) and uptake rate (k) for choline in the caudate and anterior hypothalamus were calculated using a model for point source diffusion coupled with first-order uptake kinetics. The effect of the sensors' response time on the measurements was removed by deconvolution. The D and k were 1.8 +/- 0.1 x 10(-6) cm2/s and 2.0 +/- 0.1 x 10(-2) s-1 in the caudate and 1.9 +/- 0.1 x 10(-6) cm2/s and 3.2 +/- 0.6 x 10(-2) s-1 in the anterior hypothalamus. The reduced diffusion coefficient determined in brain tissue compared to agar gel is consistent with the increased tortuosity of the brain microenvironment. A substance in brain tissue, presumably acetylcholinesterase, prevents the use of differential measurements of acetylcholine because choline sensors became sensitive to acetylcholine.     

Flupirtine protects neurons against excitotoxic or ischemic damage and inhibits the increase in cytosolic Ca2+ concentration

We tested the effect of flupirtine against ischemic and excitotoxic neuronal damage as well as on the glutamate-induced rise in cytosolic calcium ion concentration (= [Ca2+]i). For in vivo experiments we used a model of focal cerebral ischemia in mice. The middle cerebral artery was permanently occluded and 48 h afterwards brain tissue was stained with neutral red, perfusion-fixed and the infarct surface was determined planimetrically. Pretreatment with flupirtine significantly reduced the infarct area (controls: 24.3 +/- 4.8 mm2, 1 mg/kg flupirtine: 20.1 +/- 3.6 mm2 and 10 mg/kg flupirtine: 19.5 +/- 3.9 mm2; P < 0.05), whereas postischemic application of flupirtine failed to reduce the infarct area. For in vitro studies, primary neuronal cultures were prepared from the hippocampi of newborn rats and excitotoxic damage was induced by exposing the cells to 500 mu M L-glutamate for 30 min. We could demonstrate that flupirtine (1-10 microM) was capable of protecting neurons against glutamate-induced cytotoxicity. In order to elucidate the underlying mechanism of action, we tested the effect of flupirtine on the glutamate-induced rise in [Ca2+]i using the Ca2+-indicator fura-2. L-Glutamate added in a final concentration of 100 microM to the cultured cells for 16 s caused a rise in [Ca2+]i from about 100 nM to 900 nM. Flupirtine (0.1-10 microM) reduced the glutamate-induced rise in [Ca2+]i concentration dependently.     

Quantitative thermal perception testing in 225 children and juveniles

A sibling of three year old girl and a year old boy, showed delayed post-anoxic encephlopathy after strangulation. After three days of the accident, the girl developed tetraplegia and choreo-athetosis. Her brother also developed choreo-athetosis two weeks after strangulation. T2 weighted MRI revealed a high signal intensity in the bilateral putamen and caudate nucleus. After hyperbaric oxygen therapy for two months, their symptoms diminished. We hypothesize that the functional damage of the neurons occurred in the bilateral basal ganglia as delayed neuronal death because of their vulnerability and peculiarity of the local circulation. Hyperbaric oxygen therapy may be effective in rescuing the neurons from hypoxia.     

123I]beta-CIT and SPECT in essential tremor and Parkinson's disease

Resting and postural tremor may occur in essential tremor (ET) and Parkinson's disease (PD). The aim of the present study was to investigate the cocaine derivative [123I]beta-CIT, which labels striatal dopamine transporters, and SPECT in differentiating these diseases. METHODS: 30 healthy volunteers, 32 patients with ET and 29 patients with idiopathic PD of Hoehn/Yahr stage I were investigated. Specific over nondisplaceable binding ratios (target/cerebellum-1) were calculated for the striatum, the caudate nucleus and the putamen separately as well as a ratio putamen/caudate and the percent deviation of each patient's ratio from age-expected control values. RESULTS: Striatal [123I]beta-CIT binding ratios in ET were within normal ranges and showed only a discrete elevation to age-expected control values (+14.6%). In PD significantly reduced specific binding was evident not only contralaterally to the clinically affected side (putamen: -62%, caudate nucleus: -35%), but also ipsilaterally (putamen: -45%, caudate nucleus: -22%). All investigated parameters differed significantly between PD and controls and ET respectively. CONCLUSION: Imaging striatal dopamine transporters with [123I]beta-CIT and SPECT could clearly distinguish between ET and PD in an early stage of the disease. Findings do not suggest a subclinical involvement of dopaminergic nigrostriatal neurons in ET.     

Biotransformation of 17-alkylsteroids in the equine: gas chromatographic-mass spectral identification of ten intermediate metabolites of methyltestosterone

Parenterally administered domoic acid, a structural analog of the excitatory amino acids glutamic acid and kainic acid, has specific effects on brain histology in rats, as measured using different anatomic markers. Domoic acid-induced convulsions affects limbic structures such as hippocampus and entorhinal cortex, and different anatomic markers can detect these neurotoxic effects to varying degrees. Here we report effects of domoic acid administration on quantitative indicators of brain metabolism and gliosis. Domoic acid, 2.25 mg/kg i.p., caused stereotyped behavior and convulsions in approximately 60% of rats which received it. Six to eight days after domoic acid or vehicle administration, the animals were processed to measure regional brain incorporation of the long-chain fatty acids [1-(14)C]arachidonic acid ([14C]AA) and [9,10-(3)H]palmitic acid ([3H]PA), or regional cerebral glucose utilization (rCMRglc) using 2-[1-(14)C]deoxy-D-glucose, by quantitative autoradiography. Others rats were processed to measure brain glial fibrillary acidic protein (GFAP) by enzyme-linked immunosorbent assay. Domoic acid increased GFAP in the anterior portion of cerebral cortex, the caudate putamen and thalamus compared with vehicle. However, in rats that convulsed after domoic acid GFAP was significantly increased throughout the cerebral cortex, as well as in the hippocampus, septum, caudate putamen, and thalamus. Domoic acid, in the absence of convulsions, decreased relative [14C]AA incorporation in the claustrum and pyramidal cell layer of the hippocampus compared with vehicle-injected controls. In the presence of convulsions, relative [14C]AA incorporation was decreased in hippocampus regions CA1 and CA2. Uptake of [3H]PA into brain was unaffected. Relative rCMRglc decreased in entorhinal cortex following domoic acid administration with or without convulsions. These results suggest that acute domoic acid exposure affects discrete brain circuits by inducing convulsions, and that domoic acid-induced convulsions cause chronic effects on brain function that are reflected in altered fatty acid metabolism and gliosis.     

D2-family receptor distribution in human postmortem tissue: an autoradiographic study

The distribution throughout the normal human brain of the dopamine D2-family of receptors were investigated autoradiographically. Three ligands were used, [3H]-YM-09151-2 to define the D2, D3, D4 receptors; [3H]raclopride the D2 D3 receptors; and [3H](+)-7-OH-DPAT, in the presence of GTP, demonstrates D3 distribution. [3H]-YM-09151-2 and [3H]raclopride binding were highest in caudate (121 vs 130 fmol mg(-1)), putamen (96 vs 136 fmol mg(-1)), and nucleus accumbens (113 vs 120 fmol mg(-1)). [3H]-YM-09151-2 also displayed significant binding in several cortical areas (56-39 fmol mg(-1)) and hippocampus (27 fmol mg-1). [3H](+)-7-OH-DPAT was highest in the nucleus accumbens. Based upon the ligands properties it is inferred that D2 distribution is highest in putamen, caudate and nucleus accumbens; D3 in the nucleus accumbens; D4 receptor in cortical areas and hippocampus.     

3H]paroxetine binding is altered in the hippocampus but not the frontal cortex or caudate nucleus from subjects with schizophrenia

[3H]Paroxetine binding to particulate membrane from tissue, obtained at autopsy, from the hippocampus, frontal cortex, and caudate nucleus from subjects who had or had not had schizophrenia was measured. The density of [3H]paroxetine binding to membranes from subjects who had or had not had schizophrenia did not differ. Similarly, the affinity of [3H]paroxetine binding in the frontal cortex and caudate nucleus was not different. By contrast, the affinity of [3H]paroxetine binding to hippocampal membrane from subjects who had schizophrenia was significantly lower than the affinity of binding for the nonschizophrenic subjects (0.40 +/- 0.06 vs. 0.26 +/- 0.02; p < 0.05). As [3H]paroxetine binds to the serotonin transporter, these data suggest that the serotonin transporter is altered in the hippocampus in subjects with schizophrenia.     

Modification of [3H]MK801 binding to rat brain NMDA receptors after the administration of a convulsant drug and an adenosine analogue: a quantitative autoradiographic study

Specific [3H]MK801 binding to rat brain NMDA receptors after the administration of the convulsant drug 3-mercaptopropionic acid (MP) and the adenosine analogue cyclopentyladenosine (CPA) was studied by means of a quantitative autoradiographic method. MP administration (150 mg/kg, i.p.) caused significant decreases in [3H]MK801 binding in several hippocampus subareas and layers, mainly in CA1 and CA3 at seizure (11-27%) and postseizure (8-16%) and in cerebral occipital cortex at seizure (18-22%). In nucleus accumbens, a rise was observed at postseizure (44%) and a tendency to increase at seizure (24%). CPA (2mg/kg, i.p.) decreased ligand binding in hippocampus (CAI, CA2, CA3) (17-22%) and in occipital cerebral cortex (18-24%). When CPA was administered 30 minutes before MP (which delayed seizure onset) and rats were sacrificed at seizure, decreases in [3H]MK801 binding in several layers of CA1 and CA3 of hippocampus (11-27%) and in CA1, CA2, CA3 (24-35%) after CPA+MP postseizure, and an increase in CA2 after CPA and CPA+MP postseizure (20-34%), were observed. A drop was found in the occipital subarea (18-24%) after CPA and in the frontal and occipital subarea after CPA+MP postseizure (24-34%) while no changes were observed in any treatment involving the other cerebral cortex regions, thalamic nuclei, caudate putamen and olfactory tubercle. These results show that [3H]MK801 binding changes according to drug treatment and the area being studied, thus indicating a different role in seizure activity.     

Changes of relaxation times (T1, T2) and apparent diffusion coefficient after permanent middle cerebral artery occlusion in the rat: temporal evolution, regional extent, and comparison with histology

The quantitative NMR parameters T1, T2, rho, and apparent diffusion coefficient (ADC) were determined during the 7 h after middle cerebral artery occlusion in rats. In the normal caudate-putamen (CP), 869 +/- 145 ms and 72 +/- 2 ms for T1 and for T2, respectively, were found; the corresponding values for cortex were 928 +/- 117 ms and 73 +/- 2 ms. The ADC showed significant dependence on gradient direction: diffusion along x resulted in 534 +/- 53 microns 2/s (CP) and 554 +/- 62 microns 2/s (cortex), and along y in 697 +/- 58 microns 2/s (CP) and 675 +/- 53 microns 2/s (cortex). In the ischemic territory, a continuous increase over time of both relaxation times was observed in the CP, leading to an increase of 29 +/- 20% (T1) and 51 +/- 41% (T2) above control level. ADC dropped to 63 +/- 15% of control in the CP and to 74 +/- 4% of control in the temporal cortex. No significant change was noted in proton density during the observation period. Strongest ADC reduction was in the center of the ischemic territory (< or = 60% of control) surrounded by a region of lesser reduction (< or = 80% of control). During the early part of the study, the area of reduced ADC was larger than that of elevated relaxation times. Toward the end of the experiment, the area of increased relaxation times approached that of decreased ADC at < or = 80% of control. Good agreement of histological presentation of infarct with the total area of decreased ADC (< or = 80%) was demonstrated.     

Efficacy of neoadjuvant chemotherapy in primary non-small cell lung cancer

PURPOSE: To examine the changes in ciliary body thickness after topical application of pilocarpine, cyclopentolate hydrochloride, and PhXA41, a prostaglandin F2alpha analog. METHOD: We used high-frequency Humphrey UBM840 ultrasound biomicroscope to examine 36 healthy young Japanese subjects. RESULTS: The mean ciliary body thickness increased from 0.67 +/- 0.07 mm to 0.073 +/- 0.08 mm (P < .01) after application of 2% pilocarpine; 1% cyclopentolate hydrochloride and 0.005% PhXA41 decreased the mean ciliary body thickness from 0.75 +/- 0.07 mm to 0.69 +/- 0.05 mm (P < .05) and from 0.78 +/- 0.06 mm to 0.75 +/- 0.06 mm (P < .01), respectively. CONCLUSIONS: Our ultrasound study clearly indicates that pilocarpine increased comparative thickness of the ciliary body by 8.3%, whereas PhXA41 decreased comparative thickness by 3.3% in a manner similar to cyclopentolate hydrochloride.     

Fatty acid incorporation depicts brain activity in a rat model of Parkinson's disease

Following pulse labeling with [3H]arachidonic acid ([3H]AA), its incorporation pattern in brain reflects regional changes in neurotransmitter signal transduction using phospholipase A2, that is, functional activity. In a rat model of Parkinson's disease, unilateral 6-hydroxydopamine lesion in the substantia nigra, [3H]AA acid incorporation from blood was increased in cerebral cortex, caudate putamen, globus pallidus, entopeduncular nucleus, subthalamic nucleus and substantia nigra pars reticulata ipsilateral to the lesion. This increased [3H]AA incorporation likely reflects disinhibition of basal ganglia and cortical circuits secondary to absent inhibitory nigrostriatal dopaminergic input.     

Serotonin modulation of low-affinity ouabain binding in rat brain determined by quantitative autoradiography

Previous results showed that Na+/K+-ATPase may have a functional relationship with the neurotransmitter serotonin which activates the glial sodium pump in the rat brain. Both the reaction rate (V) of Na+/K+-ATPase activity and [3H]ouabain binding were significantly increased in the presence of serotonin. It is not known, however, which alpha isoform is involved in the Na+/K+-ATPase response to serotonin and its regional distribution. Quantitative autoradiography of [3H]ouabain binding to rat brain slices was employed at different [3H]ouabain concentrations in order to gain information on both the distribution and the possible isoform involved. The results showed that 1500 nM [3H]ouabain binding was sensitive to serotonin 10(-3) M and significantly increased in the following brain regions: frontal cortex, areas CA1, CA2, and CA3 of the hippocampus, presubiculum, zona incerta, caudate putamen and the amygdaloid area, confirming and extending previous results. An effect of serotonin on brain but not kidney tissue at high, 1500 nM, and the lack of effect at low, 50 nM [3H]ouabain concentrations, strongly suggests the participation of the alpha2 isoform in the response of the pump to the neurotransmitter. Glial cells showed stimulation of ouabain binding by serotonin at ouabain concentrations above 350 nM. The present results open interesting questions related to the brain regions involved and the K+ handling by the glial alpha2 isoform of the pump.