Carlo Benassi

Ketamine effects on local cerebral blood flow and metabolism in the rat.

The effects of an anesthetic dose (100 mg/kg) of ketamine, a phencyclidine derivative, on local rates of cerebral glucose utilization (LCGU) and CBF (LCBF) have been investigated by the quantitative [14C]2-deoxyglucose and [14C]iodoantipyrine techniques in the unparalyzed, spontaneously breathing rat. In ketamine-injected animals, LCGU was significantly increased in some limbic structures and decreased in inferior colliculus, vestibular, and cerebellar nuclei. The degree and spatial distribution of drug-induced changes was similar for local blood flow rates, LCBF being increased in limbic regions and decreased in the inferior colliculus. Although PaCO2 values were higher in anesthetized animals, the pattern of LCBF/LCGU ratios was not significantly affected by ketamine in the 36 brain regions examined in this study. So, at least in the rat and at the anesthetic level studied here, a net vasodilatory in vivo effect was not observed. These results support the hypothesis that CBF changes induced by the drug in animals and man are primarily related to the metabolic effects exerted by ketamine on cerebral structures.

Tonic pain time-dependently affects β-endorphin-like immunoreactivity in the ventral periaqueductal gray matter of the rat brain

beta-Endorphin-like immunoreactivity (B-EP-LI) levels have been investigated in the ventral periaqueductal gray matter (vPAG) of rats killed 30, 60 or 120 min after the subcutaneous injection of dilute formalin (0.08 ml, 5%) in one fore- or hindpaw, or comparable handling. B-EP-LI was estimated by radioimmunoassay, using an anti-camel B-EP serum directed against the C-terminal portion of B-EP molecule. In both fore- and hindlimb groups vPAG B-EP-LI values were significantly increased 60 and 120 min after the injection relative to controls. Values from animals killed 120 min after formalin injection were higher than the ones at 30 and 60 min, forelimb effects being quantitatively more pronounced. The increase in B-EP-LI appeared distributed along the whole rostrocaudal extent of the region.

Hybrid stabilization of planar linear systems with one-dimensional outputs

Abstract We consider a linear control system x ′= Ax + Bu with output y = Cx , where x∈ R 2 , u, y∈ R , and give necessary and sufficient conditions in order that it can be stabilized by a hybrid, linear feedback, where the action of the “switch” just depends on the sign of y. We also show, on these conditions, that the use of two control functions is enough for getting the goal.

Neural circuits underlying ketamine induced oculomotor behavior in the rat: 2-deoxyglucose studies

Abstract Time-related changes in oculomotor function and of metabolic activity patterns in selected brain networks, as assessed by the quantitative 2-deoxyglucose technique, were investigated in Long-Evans rats following intraperitoneal administration of a ketamine anesthetic dose. During ketamine-induced anesthesia a nystagmic-like behavior was present, characterized by unidirectional slow ocular drifts with superimposed paroxystic bursts of quick (saccadic-like) eye movements; all quick movements were executed in the horizontal direction, were strictly confined to an ocular hemifield of vision, and were followed by a backward (centripetal) drift. A metabolic hyperactivity was found in the dorsomedial shoulder region of the frontal cortex, corresponding to the rat saccadic cortical generator area, whereas functional activity levels were decreased in cerebellum and in several brainstem regions, including portions of the reticular formation and medial vestibular nuclei, putatively indicated as the locus of the oculomotor neural integrator. Starting 2 h after drug injection, a gradual recovery of oculomotor function occurred, with the disappearance of slow ocular drifts. However, an almost uninterrupted sequence of individual saccades was still present. Significant metabolic increases were found at this time in the cingulate and frontal cortex, basal ganglia, superior colliculus, paramedian reticular formation and oculomotor nuclei, the cerebellar vermis and paraflocculus. In medial vestibular nuclei, metabolic levels were undistinguishable from controls. These results suggest different concentration-dependent actions of ketamine on cortical and subcortical circuits involved in saccade generation and gaze holding. These effects are likely to be related at least in part to antagonism of N-methyl-d-aspartate receptor-mediated functions.

The interstitial nucleus of the superior fasciculus, posterior bundle (INSFp) in the guinea pig: another nucleus of the accessory optic system processing the vertical retinal slip signal.

As in rabbit, gerbil, and rat, the guinea pig interstitial nucleus of the superior fasciculus, posterior bundle (INSFp) is a sparse assemblage of neurons scattered among the fibers forming the fasciculus bearing this name. Most of the INSFp neurons are small and are ovoid in shape. Interspersed among these, are a few larger, elongated neurons whose density becomes greater and whose shape becomes fusiform in correspondence to the zone of transition from the superior fasciculus to the ventral part of the medial terminal nucleus (MTN). Like the MTN, the INSFp is activated by retinal-slip signals evoked by whole-field visual patterns moving in the vertical direction, as shown by the increase of 14C-2-deoxyglucose (2DG) uptake into this nucleus. At the same level of luminous flux, neither pattern moving in the horizontal direction nor the same pattern held stationary can elicit increases in the INSFp 2DG assumption. The specificity of the observed increases in metabolic rates in INSFp following vertical whole-field motion suggests that this assemblage of neurons relays visual signals used in the control of vertical optokinetic nystagmus.

Correlation between retinal afferent distribution, neuronal size, and functional activity in the guinea pig medial terminal accessory optic nucleus

SummaryThe intrinsic morpho-functional organization of the medial terminal nucleus of the accessory optic system was investigated in the guinea pig. The distribution of the retinal afferents, as assessed by the axoplasmic transport of 14C-valine, showed a remarkable asymmetry within the nucleus. Thus, while the retinal terminal field covered the entire medial terminal nucleus, by far the largest density of labeled retinofugal axon terminals was found within its dorsal division. In this same portion of the nucleus, we found the greatest density of large cells and the maximum intensity of functional activation, this latter as estimated by the increase in metabolic activity of neurons using the 14C-2-deoxyglucose autoradiographie method in the vertical and horizontal whole-field movement in the visual field.

COVARIOGRAM OF NON-CONVEX SETS

The covariogram of a compact set A contained in R^n is the function that to each x in R^n associates the volume of A intersected with (A+x). Recently it has been proved that the covariogram determines any planar convex body, in the class of all convex bodies. We extend the class of sets in which a planar convex body is determined by its covariogram. Moreover, we prove that there is no pair of non-congruent planar polyominoes consisting of less than 9 points that have equal discrete covariogram.

Olivofloccular circuit in oculomotor control: binocular optokinetic stimulation.

Abstract The metabolic activation of the olivocerebellar pathway during binocular optokinetic stimulation was studied in the guinea pig, by means of the semiquantitative 14C-2-deoxyglucose (2DG) technique. The experimental group underwent binocular horizontal stimulation, whereas the control animals were either kept in the dark or allowed to view a stationary pattern. The local metabolic activity index in the dorsal cap of the inferior olive was higher on the side contralateral to the eye that had been stimulated in the temporonasal (T-N) direction in the horizontal group; in contrast, the floccular region showed higher activity on the side ipsilateral to the T-N-stimulated eye. These findings support the involvement of the olivocerebellar pathway in the horizontal optokinetic response. A phylogenetic hypothesis is suggested to explain inconsistent results found in the literature.

Correlation between amount of retinal afferents to the pretectal nucleus of the optic tract and dorsal terminal accessory optic nucleus and performance of horizontal optokinetic reflex in rat

Intraocular kainic acid injection in Long-Evans rats induces loss of retinal afferents to subcortical visual centers as assessed by the axoplasmic transport of [14C]valine. The optical terminal fields of the pretectal nucleus of the optic tract (NOT), superior colliculus and accessory optic system (AOS) nuclei appear particularly affected. Since NOT and the AOS dorsal terminal nucleus (DTN) represent the first relay station of the visuomotor pathway mediating horizontal optokinetic nystagmus (HOKR), we have studied the characteristics of HOKR after various degrees of retinal deafferentation of these nuclei induced by intraocular KA injection. Taking advantage of the arrangement of the primary optic projections to NOT-DTN, that in rats are almost entirely crossed, in each animal, monocular HOKR induced by stimulation of the injected eye was compared to monocular HOKR elicited by stimulation of the intact, ipsilateral eye. Following NOT-DTN optic denervation, HOKR gain always worsened, and in a way, that the greater the deficits of retinal afferents, the greater the HOKR inability to compensate for visual motion. Furthermore, for any given retinal denervation the higher the stimulus velocity, the greater the HOKR deficit. While the correlation between HOKR gain and the amount of retinal afferents to NOT-DTN would seem to indicate a functional homogeneity of the retinal ganglion cells sending axons to these nuclei, the finding that the extent of HOKR impairment also varied with velocity might not support the above view.

Spatio-Temporal Pattern of Eye Movements Induced by Ketamine in the Rat

Eye movements up to seven hours after ketamine injection were recorded in Long-Evans rats by means of a phase detection search coil apparatus. A flutter-like oculomotor pattern immediately appeared after drug administration lasting about one hour and was characterized by unidirectional slow eye movements with superimposed bursts of saccades. While saccadic dynamics was always within the normal range, the eyes were unable to maintain a steady post-saccadic position. Every saccade was followed by a quick drift back towards the initial position. As the rat aroused, paroxysmal ocular motility stopped and spontaneous well isolated, now bidirectional saccades appeared. The post-saccadic drift persisted. Ocular flutter-like behavior could result from a sustained activation of the saccade generator, whereas impairment of gaze holding might be due to the neural integrator suppression.