Subfornical organ efferents to neural systems for control of body water.

The subfornical organ, a circumventricular structure of the central nervous system, has efferent neural projections to sites within the brain known to be involved in drinking behavior and secretion of antidiuretic hormone. By using anterograde tracing techniques, it is shown that the subfornical organ projects to the nucleus medians of the medial preoptic area, to the organum vasculosum of the lamina terminalis, and to the supraoptic nuclei bilaterally. Its efferent connectivity is confirmed by retrograde transport of horseradish peroxidase. The organum vasculosum of the lamina terminalis, another circumventricular organ and a suspected receptor site for angiotensin II, is involved in the circuitry of the subfornical organ and also has an efferent projection to the supraoptic nuclei.

Do acute diffusion- and perfusion-weighted MRI lesions identify final infarct volume in ischemic stroke?

BACKGROUND AND PURPOSE: An acute mismatch on diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) may represent the "tissue-at-risk." It is unclear which "semiquantitative" perfusion parameter most closely identifies final infarct volume. METHODS: Acute stroke patients underwent DWI and PWI (dynamic-susceptibility contrast imaging) on admission (baseline), and T2-weighted imaging (T2WI) at 1 or 3 months after stroke. "Semiquantitative" mean transit time (MTTsq=first moment of concentration/time curve), cerebral blood volume (CBVsq=area under concentration/time curve), and cerebral blood flow (CBFsq=CBVsq/MTTsq) were calculated. DWI and PWI lesions were measured at baseline and final infarct volume on T2WI acquired > or =1 month after stroke. Baseline DWI, CBFsq, and MTTsq lesion volumes were compared with final T2WI lesion volume. RESULTS: Among 46 patients, baseline DWI and CBFsq lesions were not significantly different from final T2WI lesion volume, but baseline MTTsq lesions were significantly larger. The correlation with final T2WI lesion volume was strongest for DWI (Spearman rank correlation coefficient rho=0.68), intermediate for CBFsq (rho=0.55), and weakest for MTTsq (rho=0.49) baseline lesion volumes. Neither DWI/CBFsq nor DWI/MTTsq mismatch predicted lesion growth; lesion growth was equally common in those with and without mismatch. CONCLUSIONS: Of the 2 PWI parameters, CBFsq lesions most closely identifies, and MTTsq overestimates, final T2WI lesion volume. "DWI/PWI mismatch" does not identify lesion growth. Patients without "DWI/PWI mismatch" are equally likely to have lesion growth as those with mismatch and should not be excluded from acute stroke treatment.

A new model of localized ischemia in rat somatosensory cortex produced by cortical compression.

BACKGROUND AND PURPOSE: Because of its precise connectivity and functional specificity, the rat whisker-barrel system offers an excellent opportunity to study experience-dependent neuroplasticity. However, data are lacking regarding the neuroplasticity of this system after cerebral ischemia. The purpose of the present study was to develop a reproducible model for the production of ischemia/reperfusion of the posteromedial barrel subfield (PMBSF) in the rat, which is the visible representation of the large whiskers on the opposite face. METHODS: Focal cortical ischemia was induced in male Sprague-Dawley rats (n=40) by slowly compressing the intact dura (maximum 0.05 mm/s) with a 4- or 5-mm-diameter brass cylinder equipped with a laser-Doppler probe, combined with ipsilateral common carotid artery occlusion. The microvascular blood flow of PMBSF during compression ischemia was maintained at 18% to 20% of baseline flow for 1 hour. The total infarction volume was measured by 2,3,5-triphenyltetrazolium chloride staining at several reperfusion times, and pathological examination was performed on hematoxylin-eosin-stained sections. RESULTS: The infarct volumes were 36.5+/-9.2 (n=9), 40.7+/-7.7 (n=7), and 36.6+/-6.4 mm(3) (n=5) at 24 hours, 72 hours, and 7 days after ischemia, respectively, with no significant differences among these values. There was no evidence of damage to white matter or to deep gray matter and no evidence of hemorrhage. The topographic distribution of the damaged tissue was in good agreement with that of PMBSF. CONCLUSIONS: This stroke model produces a highly consistent cortical infarct in PMBSF and can facilitate the study of behavioral, functional, and structural consequences after cerebral ischemia/reperfusion in the rat somatosensory cortex.

Projections to the inferior olive of the cat. II. Comparisons of input from the gracile, cuneate and the spinal trigeminal nuclei.

The present experiments compared the projections to the inferior olive of the cat from the gracile, cuneate and spinal trigeminal nuclei. A differential labeling strategy was used for these comparisons. It was found that all three somatic sensory nuclei project to portions of all three major divisions of the contralateral inferior olive. The spinal trigeminal n. may also project less densely to the ipsilateral medial accessory olive. Projections to the dorsal accessory nucleus (DAO) and the medially-adjacent ventral lamella of the principal nucleus are roughly somatotopically organized. Although there is considerable overlap between the projection zones, the gracile n. projects predominantly to lateral DAO, the cuneate n. projects predominantly to medial DAO, and the spinal trigeminal nucleus pars caudalis projects predominantly to the most medial portions of DAO and the ventral lamella of principal olive. Projections to the medial accessory olive, on the other hand, are not as highly organized. Instead, they overlap extensively within a small egg-shaped area in the middle of the caudal half of the nucleus. Whereas all portions of the gracile and cuneate nuclei project to the inferior olive, only the pars caudalis of the spinal trigeminal nucleus appears to do so. These results were compared with the three available olivocerebellar maps as well as with the available behavioral and electrophysiological evidence on cerebellar somatotopic organization. This comparison indicated that the inputs to the cerebellum from the three second-order somatosensory nuclei via the inferior olive appear to be generally consistent with cerebellar somatotopic organization. This consistency is apparent not only with respect to the longitudinally-organized, vermal and paravermal differences in the anterior lobe, but also with respect to the transversely-organized specific somatotopy of the intermediate zone of the anterior lobe and the paramedian lobule.

The efferent connections of the feline nucleus cuneatus.

Nucleus cuneatus projections to nucleus ventralis posterolarteralis pars medialis (VPLm) and other thalamic as well as midbrain and medullary nuclei were studied in cats using the Fink-Heimer I silver technique. Single electrolytic lesions of very small size were made stereotaxically in different zones of nucleus cuneatus under electrophysiological control. All zones studied projected to contralateral VPLm in a pattern of discrete terminal arborizations or clusters, which were organized in onionskin-like dorso-ventral laminae. The clusters of degeneration varied in size and density according to their dorsoventral location within VPLm. Those in dorsal areas were smaller in diameter (50-125 mu) and contained less dense amounts of degeneration than clusters (150-300 mu) in more ventral regions. The clustered terminal arborizations mirrored the organization of the VPLm neuronal clusters, themselves. Terminations within VPLm were topographically organized, but were completely inverted, i.e. dorsal nucleus cuneatus projected to ventral VPLm and ventral to dorsal, lateral to medial, and medial to lateral VPLm. A ventral zone of nucleus cuneatus, which contained "deep" units, projected to a separate dorsal zone of VPLm. In addition to its classical connection with VPLm, nucleus cuneatus projected to the following contralateral brainstem or thalamic nuclei: medial and dorsal accessory olives, external nucleus of the inferior colliculus, ventrolateral part of the superior colliculus, nucleus ruber, medial geniculate nucleus pars magnocellularis, suprageniculatus, medial and lateral divisions of the posterior thalamic nuclear group, zona incerta, and Fields of Forel. Very sparse amounts of degeneration were also present within nuclei ventralis posteromedialis (caudal pole) and ventralis posterolateralis pars lateralis. The brain-stem and thalamic projections of the dorsocaudal part (cell nest region) of the cuneate nucleus were more restricted than those of its rostral and ventral regions. The clusters of both the VPLm neurons and cuneate terminations within VPLm provides an anatomical basis for the functional characteristics of synaptic security, fine grain somatotopia and modality specificity so prominent in the dorsal column nuclei-medial lemniscal system.

First somatosensory cortical columns and associated neuronal clusters of nucleus ventralis posterolateralis of the cat: an anatomical demonstration.

Microlesions (30--275 microns in diameter) were placed in VPLm of the cat and the terminal axonal degeneration in SI cortex was stained using the Fink-Heimer I technique. Following each of these microlesions, small, localized patches or subcolumns of degeneration, relatively light in density, were observed within laminae IIIb and IV of SI when viewed in the coronal plane. In addition, a few degenerating fibers ascended to lamina I. These multiple subcolumns had distinct radial boundaries and were narrow in the mediolateral plane (80--120 microns in width) but elongated rostro-caudally (2500--3000 microns in length). Localized patches of degeneration were separated at their widest points by a distance of 500 microns medio--laterally, but at various rostro--caudal levels of SI were observed to merge into larger columns of degeneration (250--400 microns) and then separate again into smaller multiple patches (i.e., a "zebra-like" pattern). Small injections of HRP into the forelimb region of area 3b or rostral area 1--2 of SI resulted in the labeling of small, discrete clusters of neurons in the ventral regions of VPLm. The clusters examined ranged in size from 140--350 microns in medio--lateral diameter and were elongated rostro--caudally (up to 500 microns in extent); virtually all cells within a cluster appeared labeled, but not equally so. A pattern of HRP labeling different from that observed following area 3b and rostral area 1--2 injections was observed following injections into more caudal regions of area 1--2 and into SII cortex. The labeling that resulted from these injections was not in the form of neuronal clusters but instead labeled cells tended to be scattered in more dorsal regions of VPLm. This scattering did not appear to be random since the labeled neurons were grouped within the same general area of VPLm. Labeling was distributed throughout a number of cell clusters, comprising only a small proportion of cells within each cluster. The pattern of labeling seen after caudal area 1--2 and SII injections differed only in its rostro--caudal extent within VPLm. SII injections generally resulted in labeling along the full rostro--caudal dimension of VPLm. A differential organization of the anatomy of thalamocortical projections to the various subdivisions of SI and to SII was noted in this study. It is postulated that the multiple, discrete patches of degeneration in laminae IIIb and IV of SI represent a portion of the somatosensory cortical columns and that the HRP-labeled clusters seen in VPLm following area 3b and rostral area 1--2 are the subcortical equivalents of these subcolumns.

Representation of a single vibrissa in the rat neostriatum: peaks of energy metabolism reveal a distributed functional module.

In unanaesthetized rats, mechanical stimulation of a single vibrissa increased glucose utilization in one cortical column of the somatosensory area and in several spots in the dorsolateral neostriatum, predominantly on the side contralateral to the stimulation. Two or three peaks of glucose utilization unique to the stimulated animals were seen in cross sections throughout a 1.8 mm anteroposterior extent in the dorsolateral striatum. These observations suggest that one cortical column is functionally related to several neostriatal regions. The distributed modularity may be an important characteristic of the basal ganglia system.

Efferent projections of the gracile nucleus in the cat.

The efferent projections of different portions of the gracile nucleus in the cat were studied using both autoradiographic and degeneration tracing methods. The results suggest that there are two aspects to the functional organization of these projections. First, the somatotopic organization of the gracile n. (GR) is maintained, but inverted, by the topographic organization of its projections to VPL1. Fibers from the lateral portions of GR terminate medially in VPL1; fibers from the dorsal portions terminate ventrally. These fibers, especially those from the middle and caudal portions of GR, terminate in dense, precisely located groups of clusters. Dorsally located clusters in VPL1 (predominantly from middle-ventral portions of GR) are significantly smaller than ventrally located clusters (predominantly from middle-dorsal portions). The second aspect of this organization, involving the projections both to VPL1 and to other brain stem targets, is that some kind of functionally relevant sorting process appears to occur as fibers leave different portions of the gracile n. The afferent projections of the rostral (GRr) and middle-ventral portions (GRmv) of the gracile n. are different from those from the other portions of the nucleus. Projections to VPL1 from GRr are less dense, less likely to form clusters, less clearly topographically organized, and extend further rostrally and dorsally in VPL1 than those from the rest of GR. The clusters are small, like those from GRmv. Similarly, although all portions of GR project to several other brain stem regions, these projections appear to be derived preferentially from GRr and/or GRmv. These brain stem regions involve certain portions of the inferior olive, inferior and superior colliculi, red n., zona incerta, pretectum, thalamic posterior group and the H field of Forel. This dual organization of efferent connectivity is similar to that of the cuneate n.20, and is consistent with many of the differences in cytoarchitecture, afferent connectivity and response properties of cells within different portions of the dorsal column nuclei.

The role of norepinephrine in adult rat somatosensory (SmI) cortical metabolism and plasticity.

Stimulation of rat facial vibrissae increases glucose utilization in the corresponding barrels (lamina IV) and associated columns in laminae I-VIa of the contralateral first somatosensory (SmI) cortex as assessed autoradiographically by the uptake of [14C]2-deoxy-glucose (2-DG). Chronic deafferentation (2 months) by bilateral vibrissectomy with sparing of the C3 vibrissa (SC3) in adult Sprague-Dawley rats produced no change in the rate of LCGU but led to an increased areal extent of the metabolic representation of the SC3 barrel (39%, P less than 0.001) and column (31%, P less than 0.003) as compared to rats with fully intact vibrissae. In other rats with intact facial vibrissae, 6-hydroxydopamine lesions of the locus coeruleus (LC) depleted ipsilateral cortical norepinephrine (NE) by more than 90% and, 2 months later, led to an 11% and 21% increase in C3 barrel and column metabolic representations, respectively, as compared to the contralateral SmI cortex with intact NE levels (P less than 0.05). When bilateral vibrissectomy was combined with a unilateral LC lesion, the SC3 barrel and column metabolic representation on the LC-intact side enlarged as expected but no enlargement occurred on the NE-depleted side (20% difference; P less than 0.05). Therefore, the effect of NE on the SmI cortex depends on the status of its afferent input. NE inhibits the spread of metabolic activity beyond the activated barrel and column in the intact cortex, but independently modulates plastic enlargement in the partially deafferented SmI cortex.

Chronic inhibition of NOS does not prevent plasticity of rat somatosensory (S1) cortex following deafferentation.

Nitric oxide (NO) has been proposed as an intercellular messenger mediating postsynaptic to presynaptic information transfer in the induction of long-term potentiation. A number of studies support the possible involvement of NO in synaptic plasticity. NO may have a role in synaptogenesis and synaptic plasticity in developing rat brain and may play a fundamental part in the process of regeneration, plasticity, and retargeting of axons following injury. We examined the possible role of NO on plasticity in the rat first somatosensory cortex with [14C]2-deoxyglucose (2-DG) autoradiography in rats treated daily with l-nitroarginine (l-NA) following neonatal unilateral vibrissae deafferentation. After 6 weeks of l-NA treatment, the local cerebral glucose utilization (LCGU) and the spatial extent of the metabolic activation following stimulation of the spared whisker was measured. NOS catalytic activity exhibited significant inhibition throughout the treatment period. Vibrissae deafferentation produced a small but not statistically significant increase of LCGU in the vibrissa activated C3 barrel, and l-NA treatment did not alter the activation of LCGU in the deafferented cortex following whisker stimulation. Additionally, l-NA treatment did not alter the area of metabolic activation on either the non-deafferented side or the deafferented side. Deafferentation produced a 298% increase in the metabolic representation of the spared C3 barrel following stimulation in the saline treated animals, a 257% increase in the chronically l-NA treated animals, and a 256% increase in the short-term treated animals, all with respect to the response in the non-deafferented cortex. Metabolic plasticity in the barrel cortex was not attenuated by l-NA treatment. These results show that nitric oxide does not play a major role on developmental cortical plasticity induced by vibrissae deafferentation in the rat.

Locus coeruleus input affects glucose metabolism in activated rat barrel cortex.

Significant depletion (greater than 50%) of neocortical norepinephrine (NE), 2 weeks after unilateral 6-hydroxydopamine lesions of the locus coeruleus, led to a small (8%), ipsilateral decrease in total C3 vibrissa column 14C-2-deoxyglucose uptake, but a larger (24-32%) increase in the areal extent of this uptake into the metabolic representation of both the C3 column and barrel of the rat somatosensory (SmI) cortex during stimulation of the contralateral C3 facial vibrissae. This suggests a predominantly inhibitory role for NE in modulating SmI oxidative metabolism during physiologic stimulation.

Prevalence of disease in nonviremic cats previously exposed to feline leukemia virus.

Feline leukemia virus status and antibody titer to feline oncornavirus-associated cell membrane antigen (FOCMA) were determined on plasma from 183 outpatient cats and 61 cats from 2 closed, FeLV-positive, multiple-cat households. Cats with FOCMA antibody titer had a significantly (P less than 0.02) higher prevalence of history of disease than did cats without FOCMA antibody. Diseases included upper respiratory tract infections, abscesses, ear infections, lower urinary tract infections, gastrointestinal disease, pneumonia, uterine infection, lymphadenopathy, fever of unknown origin, and bacterial infections. The FOCMA antibody titer was determined by use of an indirect fluorescent antibody test; titer greater than or equal to 1:16 was considered to be positive results. Lower mean FOCMA antibody titer was observed in young cats with history of disease (P less than 0.05) than in young cats without history of disease or in older cats with or without history of disease. Prevalence of FOCMA antibody titer was identical (38%) in young and adult cats, indicating cats likely were exposed to FeLV as kittens because a higher prevalence of FOCMA antibody titer in older cats would otherwise be expected.

Effects of dexamethasone on electroacupuncture analgesia and central nervous system metabolism.

Many reports have indicated that electro-acupuncture analgesia (EAA) was mediated by endorphins. Among them is B-endorphin which can be released from the anterior lobe of the pituitary. To examine the role of B-endorphin in EAA and observe CNS metabolic (functional) and behavioral effects of dexamethasone the present study employed the (14C) 2-deoxyglycose (2DG) method. Seventeen adult male Sprague-Dawley rats in five groups received the following different types of somesthetic stimulation to examine the local cerebral glucose utilization (LCGU) and tail-flick response latency: control group (N = 3), pain group (N = 4), EA group (N = 3), pain + EA group (N = 3; from another ongoing study) and dexamethasone group (N = 4). Dexamethasone reduced tail-flick response latency in response to electroacupuncture, and produced metabolic (functional) changes in a number of CNS structures implicated in electroacupuncture produced analgesia effects (some changes were statistically significant, many others were not). Specific brain structures exhibiting statistically significant changes (p less than 0.05) in LCGU when compared to the pain + EA group are: the parafascicular and habennlar nuclei of the thalamus and the posterior cingulate gyrus. In comparison of dexamethasone group with the other four experimental groups of rats, the following trend in LCGU changes was observed: pain + EA group greater than pain group = EA group = dexamethasone group greater than control group. In addition, dexamethasone had a sedative effect. The results suggest that dexamethasone is reducing EAA and having suppressive effects on CNS metabolism and behavior.