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PubMed2001

Rhombencephalosynapsis with massive hydrocephalus: case report and pathogenetic considerations.

Rhombencephalosynapsis (RS) is a rare cerebellar malformation characterized by vermian agenesis or hypogenesis, fusion of the hemispheres, and closely apposed or fused dentate nuclei. This report concerns a 29-year-old Caucasian female with a history of profound retardation and chronic hydrocephalus. Multiple shunts had been placed and there had been several admissions for shunt infections. Autopsy confirmed massive hydrocephalus and revealed marked aqueductal stenosis. The cerebellum was small with vermian aplasia, closely apposed dentate nuclei, fusion of the middle cerebellar peduncles, and a small fourth ventricle. Associated defects included fusion of the inferior colliculi and absence of dorsal olivary nuclei. This spectrum of anomalies is consistent with RS and could be explained by an embryological defect of dorsal pattering that affects the "isthmic organizer" at the mesencephalic-metencephalic border. Molecular analysis of dorsalizing genes, such as Lmx1a, which regulate early developmental events at the pontomesencephalic junction, may reveal a mutation or mutations unique to RS.

Adult↗

PubMed2001

Magnetic resonance imaging and three-dimensional reconstructions of the brain of a fetal common dolphin, Delphinus delphis.

To demonstrate the kinds of data that can be obtained non-destructively and non-invasively from preserved museum specimens using modern imaging technology the head region of a whole body fetal specimen of the common dolphin, Delphinus delphis, aged 8-9 months post-conception, was scanned using Magnetic Resonance Imaging (MRI). Series of scans were obtained in coronal, sagittal and horizontal planes. A digital three-dimensional reconstruction of the whole brain was prepared from the coronal series of scans. Sectional areas and three-dimensional volumes were obtained of the cerebral hemispheres and of the brainstem-plus-cerebellum. Neuroanatomical features identified in the scans include the major sulci of the cerebral hemispheres, well-differentiated regions of gray and white matter, the mesencephalic, pontine, and cervical flexures, the "foreshortened" appearance of the forebrain, and the large auditory inferior colliculi. These findings show that numerous features of the fetal common dolphin brain can be visualized and analyzed from MRI scans.

Animals↗

PubMed2004

MRI characterisation of a novel rat model of focal astrocyte loss.

Blood-brain barrier (BBB) integrity is lost in several neurological conditions in which astrocytes are damaged. We studied 3-chloropropanediol-induced focal lesions, a toxicant that induces early astrocytic (but not neuronal) death followed by BBB leakage. T2-weighted images illustrate regional selectivity of the lesions, affected areas including the inferior colliculi and red nuclei. Gd-DTPA intensity quantified the degree of vascular leakage in the lesioned areas. MRI intensity in lesioned areas peaked at 2 days, correlating with BBB breakdown, and diminished thereafter, returning to pre-injection levels by 30 days in parallel with the return of astrocytes. T2 measurements were unchanged at 6 h, a time when astrocyte swelling is marked but the vasculature is intact, but increased at 2 days, consistent with cellular damage and BBB leakage. Gd-DTPA enhancement was also greatest at 2 days then decreased over the next 28 days, indicating a tracer-size-dependent rate of BBB repair. A simple model based on experimentally acquired data indicated that the vascular breakdown was the result of leakage of only a small percentage of blood vessels in the affected areas. Loss of astrocytes contributes to barrier loss, and restoration of astrocytes is needed for full barrier recovery.

Animals↗

PubMed1991

Alterations of local cerebral blood flow and glucose uptake by electroconvulsive shock in rats.

The effects of single and repeated electroconvulsive shock (ECS) treatment on regional cerebral blood flow (rCBF) and on rates of glucose flow from blood to local brain areas (rCGF), were investigated in pentobarbital-anesthetized rats, using quantitative autoradiographic techniques. Effects of single ECS on rCBF were assessed at two average time points of 15 and 55 sec after the application of the electric current, whereas the effects on rCGF were assessed at 70 and 110 sec. Effects of repeated ECS were assessed 24 hr after the last ECS in a series of eight daily treatments. Single ECS caused marked increases in rCGF in different brain structures, but no significant effects were observed after repeated ECS. Similarly, substantial increases in rCBF were seen during and immediately after the ECS-induced seizure, but not 24 hr after the last treatment of repeated ECS. Single ECS appeared to have differential effects on rCBF in hind-brain structures as compared to more anterior regions. A linear relationship between rCBF and rCGF values was established in control animals, indicating coupling of these two variables with a constant rCBF/rCGF ratio. ECS caused an apparent increase in the CBF/CGF ratio, which might be attributed to the different temporal resolution of the two methods used here to estimate rCGF and rCBF. Analysis of the increments of rCGF and rCBF extrapolated to the same point in time after a single ECS (10 sec), revealed that in many of the examined structures the CBF/CGF ratio was similar to that observed in control animals, indicating that the coupling of CBF and CGF is maintained during the seizure. But in some brain stem structures such as the dorsal raphe, inferior colliculi, superior olivary nucleus, and the vestibular nucleus there were large increases in CGF associated with a marked drop in the CBF/CGF ratio. This observation suggests that high metabolic demands can be met by increased local blood flow up to a given "ceiling" keeping the glucose clearance from blood to brain tissue constant. However, when the metabolic demands exceed this upper limit, the additional demands could be met by an increased clearance of glucose without a change in CBF.

Animals↗

PubMed1976

Relative cerebral glucose uptake of neuronal perikarya and neuropil determined with 2-deoxyglucose in resting and swimming rat.

An autoradiographic method using tracer amounts of [14C]-2-deoxy-D-glucose (2-DG) was used to detect areas of the brain in which glucose consumption was altered in swimming as compared to resting rats. Areas in which changes occurred in the swimming rat were widespread in gray matter, being greatest in the cerebellar vermis and least in portions of the cerebellar hemispheres and the inferior colliculi. Improved resolution was obtained with an autoradiographic method for [3H]-2-DG. The number of grains per unit area over neuronal perikarya was either slightly greater or equal to that over the immediately surrounding neuropil in both resting and swimming rats. This indicated that the glucose consumption of neuronal perikarya and the immediately surrounding neuropil per unit volume were similar. Since gray matter is composed predominantly of neuropil, the present results indicate that the bulk of the total brain gray matter glucose consumption is accounted for by neuropil in both the resting and swimming states.

Animals↗

PubMed1983

The termination in the mesencephalon of fibres from the lateral cervical nucleus. An anatomical study in the cat.

The termination in the dorsal mesencephalon of fibres from the lateral cervical nucleus (LCN), recently discovered with the retrograde tracing technique, was investigated by both the degeneration method and anterograde transport of lectin-conjugated horseradish peroxidase. Both strategies gave similar results. The termination area was found to be situated at the level of transition between the superior and inferior colliculi and comprises mainly the intercollicular nucleus and the deep and intermediate layers of the posterolateral pole of the superior colliculus. The functional implication of the demonstrated projection from LCN is discussed in relation to somatosensory activity in the mesencephalic tectum.

Afferent Pathways↗

PubMed1984

Distribution of immunoreactive dynorphin A1-8 in discrete nuclei of the rat brain: comparison with dynorphin A.

The distribution of immunoreactive (ir)-dynorphin A1-8 (Dyn A1-8) in 78 microdissected rat brain areas as well as in the neurointermediate lobe of pituitary gland was determined using a highly specific radioimmunoassay. The highest concentrations of Dyn A1-8 in brain were found in substantia nigra (673.8 fmol/mg protein) and lateral preoptic area (565.1 fmol/mg protein). High concentrations of ir-Dyn A1-8 (greater than 240 fmol/mg protein) were found in 5 nuclei: ventral premamillary nucleus, anterior hypothalamic nucleus, dorsomedial nucleus, arcuate nucleus, and medullary reticular nuclei. Moderate concentrations of the peptide (between 120 and 240 fmol/mg protein) were found in 55 brain nuclei such as septal and amygdaloid nuclei, most diencephalic structures, mesencephalic nuclei, pons and medulla oblongata nuclei and others. Low concentrations of ir-Dyn A1-8 (less than 120 fmol/mg protein) were found in 16 regions, e.g. frontal cortex, hippocampus, caudate-putamen cortical amygdaloid nucleus, several thalamic nuclei, mamillary body superior and inferior colliculi, cerebellar nuclei and others. The posterior thalamic nucleus has the lowest ir-Dyn A1-8 concentration (62.0 fmol/mg protein). The neurointermediate lobe of the pituitary gland is extremely rich in ir-Dyn A1-8 (4063.0 fmol/mg protein).

Animals↗

PubMed1984

Quantitative autoradiography of [3H]ouabain binding sites in rat brain.

In vitro quantitative autoradiography was used to localize in rat brain binding sites for [3H]ouabain, an inhibitor of the Na+,K+-ATP-ase. High levels of [3H]ouabain binding sites were found in the superior and inferior colliculi, the mammillary nucleus, the interpeduncular nucleus, and in various divisions of the olfactory, auditory and somatomotor systems. The heterogeneous distribution of [3H]ouabain binding closely parallels the regional brain glucose consumption as determined by the [14C]deoxyglucose method. Lesion studies of the rat hippocampus using the excitotoxin, ibotenic acid, showed both a marked decrease of neuronal cell types on the injected side and a corresponding decrease in [3H]ouabain binding, indicating that some of the [3H]ouabain binding sites are localized to neurons. The close correlation between [3H]-ouabain binding and regional glucose utilization provides further evidence for a linkage between glucose utilization and the neuronal Na+,K+-ATPase.

Animals↗

PubMed1989

Involvement of nigrotecto-reticulospinal pathways in the iminodipropionitrile (IDPN) model of spasmodic dyskinesias: a 2-deoxy-D-[1-14C]glucose study in the rat.

Chronic administration of iminodipropionitrile (IDPN) to rats causes a persistent behavioral syndrome characterized by lateral and vertical head twitches, random circling, and increased tactile and acoustic startle responses. In order to identify brain areas which are affected in rats manifesting this syndrome, we used the autoradiographic 2-deoxy-D-[1-14C]glucose ([14C]DG) method to map cerebral glucose utilization in IDPN-treated rats. One day after the development of the dyskinetic syndrome, there were significant decreases in local glucose utilization in the substantia nigra pars reticulata (SNr) and compacta (SNc), the dorsal raphe, the superficial and deep layers of the superior colliculus, the inferior colliculi, the interpeduncular nucleus, the medial and dorsolateral geniculate nuclei, and the superior and lateral vestibular nuclei. There were also significant decreases in layer 2 of the cingulate cortex and in the temporal and occipital cortices. In contrast, there were no changes in the motor cortex, the caudate-putamen, the nucleus accumbens, or the median raphe. These findings suggest that deleterious effects of IDPN on the nigrotectal pathways which affect head and neck movements and circling behaviors via the brainstem reticulospinal tracts may play an important role in the IDPN-induced persistent spasmodic dyskinetic syndrome in rats.

Animals↗

PubMed1994

Identification of nocifensor reflex-related neurons in the rostroventromedial medulla of decerebrated rats.

Extracellular single unit recordings were made from neurons in the rostroventromedial medulla of decerebrated rats. The previously described 'on-cell' and 'off-cell' classes were found in this preparation, and this classification, which is based on tail flick-related changes in activity, was not altered by the introduction or removal of halothane anesthesia. It is therefore evident that the identifying physiological properties of on- and off-cells are not dependent on the presence of anesthesia in decerebrate rats, or on brain structures rostral to the inferior colliculi.

Anesthesia↗

PubMed1994

Changes in [3H]PAF binding and PAF concentrations in gerbil brain after bilateral common carotid artery occlusion: a quantitative autoradiographic study.

This study investigated the distribution of platelet activating factor (PAF) binding sites in the brain and their involvement in global ischemia in a model of bilateral common carotid occlusion in the gerbil. In sagittal sections of gerbil brain, labeling with [3H]PAF was mainly located in the cortex, hippocampus and cerebellum. The corpus striatum, the superior and inferior colliculi showed lower binding, while the thalamus was only weakly labeled. Scatchard analysis of the data obtained from displacement curves with unlabeled PAF revealed the presence of one or two populations of binding sites with different affinity constant values depending on the brain structures. When the gerbils were submitted to 10 min ischemia, similar autoradiography with [3H]PAF demonstrated a dramatic reduction of labeling in all brain structures, particularly in the hippocampus. Immunoreactive endogenous PAF concentrations in brain tissues showed a marked increase in ischemic animals: (8977.3 +/- 1113 pg/g wet weight) as compared to sham-operated control: (997.7 +/- 77 pg/g wet weight). Endogenous PAF levels returned to basal values following 30 min reperfusion. These results indicate that PAF may be involved in the early stages of brain ischemia in the gerbil and suggest that endogenous PAF produced during ischemia may contribute to the down-regulation of [3H]PAF binding sites in the brain.

Animals↗

PubMed1996

Induction of Fos-like immunoreactivity by opioids in guinea-pig brain.

In the present study the effects of intracerebroventricular (i.c.v.) administration of 100 nmol of morphine, the selective mu-receptor agonist DAMGO, the delta-receptor agonist DPDPE and the kappa-receptor agonist U50,488H, on the induction of Fos-like immunoreactivity (Fos-LI) in the guinea-pig brain were investigated using immunohistochemical techniques. Guinea-pigs given i.c.v. injection of opioids showed marked increases in the number of Fos-LI nuclei within a large number of brain regions, several of which, including hypothalamic nuclei, paraventricular thalamic nucleus, the amygdala, periaqueductal gray, superior and inferior colliculi, the piriform and entorhinal cortices, have been shown to be activated under stressful or aversive conditions. Pretreatment with the opioid antagonist, naltrexone, before administration of morphine or U50,488H, inhibited Fos-LI induction indicating that the effects of the opioids were mediated by opioid receptors. U50,488H administration resulted in higher numbers of Fos-LI stained neurons compared to morphine in most regions other than the nucleus accumbens and interpeduncular nucleus. Morphine and DAMGO produced significantly higher numbers of Fos-LI neurons in the nucleus accumbens shell region than U50,488H, which may reflect the more powerful reinforcing/rewarding effects of mu-receptor agonists. Thus the present study supports a critical role for the nucleus accumbens shell region in the reinforcing/rewarding effects of opioids.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1978

Delimitation of neuronal substrates necessary for the analgesic action of baclofen and morphine.

The loci of neuronal substrates necessary for the analgesic action of baclofen and of morphine were determined by systematic transection of the rat cerebrospinal axis. Severe reduction in the analgesic capacity of both drugs, assessed with the tail flick test, occurred after section of the thoracic spinal cord, indicating that necessary substrates are located rostral to this level. These data also suggest that baclofen-induced analgesia does not primarily result from a pharmacological blockade of nociceptive information at the first sensory synapse in the spinal cord. Neither baclofen- nor morphine-induced analgesia was altered by transection of the brain stem between the superior and inferior colliculi, but the action of both drugs was greatly reduced following section of the medulla 3 mm rostral to the obex. Thus, the rostral margin of neuronal substrates mediating the effects of both drugs lies somewhere in the pons or anterior third of the medulla. This observation is compatible with the notion that analgesia induced by baclofen and morphine involves, at least in part, common neuronal substrates.

Aminobutyrates↗

PubMed1986

Tracer and maximal specific binding of tritiated spiperone or N-n-propylnorapomorphine to quantify dopamine receptors in rat brain regions in vivo.

Specific tracer and maximal specific binding (Bmax) were determined in rat brain regions from radioactivity accumulation after intravenous administration of 3H N-n-propylnorapomorphine (NPA) or 3H spiperone at various specific activities. With NPA the highest Bmax-values (expressed in pmol.g-1 tissue) were found in the striatum (26 pmol.g-1) nucleus accumbens (about 27 pmol.g-1) and the olfactory tubercle (11 pmol.g-1). Saturable NPA binding was also found in the amygdaloid complex, medulla oblongata and inferior colliculi, but not in the frontal cortex. Bmax values for spiperone were high in the striatum (73 pmol.g-1), the nucleus accumbens (48 pmol.g-1), the olfactory tubercle (34 pmol.g-1) and the frontal cortex (18 pmol.g-1). A similar order was found for the tracer contents in these regions. There was no linear relationship between these contents and Bmax values. The possible implications of these findings and usefulness of NPA for brain imaging are discussed.

Animals↗

PubMed1986

Abnormalities in the central cholinergic transmitter system of the genetically epilepsy-prone rat.

Seizure-experienced Genetically Epilepsy-prone Rats (GEPRs) have increased acetylcholine content and choline acetyltransferase activity in the thalamus and striatum. These cholinergic differences are accompanied by a slight but statistically significant reduction in acetylcholinesterase activity in the midbrain. In addition, no abnormalities were found in the numbers of specific 3H-QNB binding sites in the striatum, hippocampus, inferior colliculi or cortex. Other work has shown no difference in muscarinic receptor function as measured by carbachol-stimulated inositol-1-phosphate formation. These data suggest a possible presynaptic defect in the striatal and thalamic cholinergic system which may play some role in the seizure-prone state of the GEPR. However, caution must be used in interpreting these cholinergic derangements since more recent findings show no differences in thalamic acetylcholine content in seizure-naive GEPRs. Thus, the original cholinergic abnormalities detected in the seizure-experienced GEPR may be an enduring response to seizure activity.

Acetylcholine↗

PubMed1989

Comparison of the effects of central and peripheral aluminum administration on regional 2-deoxy-D-glucose incorporation in the rat brain.

Intracerebroventricular (ICV) Injection of aluminum tartrate (ALT 205.7 mcg) in the rat induces a progressive encephalopathy characterized by neurobehavioral derangements, by the slowing of the background rhythm of the quantitative electroencephalogram and by learning and memory deficits. The condition, lethal within about 35 days, is associated with a reduced ability of cerebral synaptosomes to incorporate radiolabeled 2-Deoxy-D-glucose (2DG) in vitro. The present study surveyed and compared the in vivo regional cerebral glucose uptake (rCGlu) capacity of rats injected with ALT 7 or 14 days previously either by the ICV or intraperitoneal (120 mg/Kg) routes. ICV injection produces transient rCGlu depression in caudate-putamen, geniculate bodies and periaquaeductal gray, resolving by day 14. Thalamic nuclei exhibit depressed rCGlu by the 7th day undergoing further depression by day 14. The rCGlu of occipitoparietal cortices, normal at day 7, was increased by day 14. In contrast, peripheral aluminum administration produced transient rCGlu depression in olfactory bulbs, frontal and occipitoparietal cortices, nucleus accumbens and cerebellum, and transiently increased rCGlu in the geniculate nuclei. These effects, present by day 7, had resolved by day 14 when rCGlu had increased in the previously normal pontine nuclei and decreased in the previously normal hippocampus. Neither treatment changed rCGlu in the septal nuclei, globus pallidus, amygdala, olfactory cortex, substantia nigra, superior or inferior colliculi or the medullary nuclei. The pattern of anomalies in cerebral 2DG incorporation most probably indexes the deranged glucoregulatory and metabolic demands of these brain areas in the aluminum intoxicated state.

Aluminum↗

PubMed1990

Impairment of auditory processing by simultaneous vestibular stimulation: psychophysical and electrophysiological data.

The aim of the experiments reported here was to demonstrate auditory-vestibular interaction both on a psychophysical and on an electrophysiological basis in humans. These results correspond to those recently obtained during simultaneous visual and vestibular stimulation and illustrate experimentally the importance of auditory information processing in spatial orientation. Time to detect the motion of a sound source is significantly increased when simultaneous vestibular stimulation is induced by passive sinusoidal head oscillations. This effect increased with the peak acceleration of the vestibular stimulus (197, 790 and 1777 degrees/s2). Vestibular influence on general auditory information processing without the quality of (object-) motion could be electrophysiologically demonstrated by means of brainstem auditory evoked potentials. The amplitude of component V generated by the inferior colliculi or by neuronal structures located slightly lower in the auditory tract was significantly reduced during concurrent vestibular stimulation. This neuronal brainstem area is a predominant location of biconvergent vestibulo-auditory neurons mediating intersensory information processing at an early neuronal level.

Adolescent↗

PubMed1994

The role of the periaqueductal grey in vocal behaviour.

This is a review of our current knowledge about the role of the periaqueductal grey (PAG) in vocal control. It shows that electrical stimulation of the PAG can evoke species-specific calls with short latency and low habituation in many mammals. The vocalization-eliciting region contains neurones the activity of which is correlated with the activity of specific laryngeal muscles. Lesioning studies show that destruction of the PAG and laterally bordering tegmentum can cause mutism without akinesia. Neuroanatomical studies reveal that the PAG lacks direct connections with the majority of phonatory motoneurone pools but is connected with the periambigual reticular formation, an area which does have direct connections with all phonatory motor nuclei. The PAG receives a glutamatergic input from several sensory areas, such as the superior and inferior colliculi, solitary tract nucleus and spinal trigeminal nucleus. Glutamatergic input, in addition, reaches it from numerous limbic structures the stimulation of which also produces vocalization, such as the anterior cingulate cortex, septum, amygdala, hypothalamus and midline thalamus. Pharmacological blocking of this glutamatergic input causes mutism. The glutamatceptive vocalization-controlling neurones are under a tonic inhibitory control from GABAergic neurones. Removal of this inhibitory input lowers the threshold for the elicitation of vocalization by external stimuli. A modulatory control on vocalization threshold is also exerted by glycinergic, opioidergic, cholinergic, histaminergic and, possibly, noradrenergic and dopaminergic afferents. It is proposed that the PAG serves as a link between sensory and motivation-controlling structures on the one hand and the periambigual reticular formation coordinating the activity of the different phonatory muscles on the other.

Animals↗