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A Wree

Publications and source records attributed to A Wree.

At least 37 records · Page 2Linked to original sources

Time course of hippocampal glucose utilization and persistence of parvalbumin immunoreactive neurons after ibotenic acid-induced lesions of the rat dentate area.

The effects of ibotenic acid induced lesions of the dentate gyrus on hippocampal glucose utilization and parvalbumin-positive neurons were evaluated in male Wistar rats. Ibotenic acid was injected in the right dorsal dentate gyrus. Quantification of glucose utilization was performed 3 days, 3 weeks, or 3 months after the lesion using the 14C-2-deoxyglucose method. Nissl-stained sections and sections stained for acetylcholinesterase were used as references for anatomical delineation of the hippocampal cytoarchitecture. Additional sections were stained for parvalbumin. The results revealed widespread reductions of glucose utilization in all layers and sectors of the hippocampus in the ipsilateral lesioned hemisphere and also in the nonlesioned contralateral hemisphere. The reductions occurred as early as 3 days after the lesion and persisted up to 3 months. In neither hippocampal structure did glucose utilization return to control levels. Immunohistochemical visualization of parvalbumin-containing neurons revealed that these putatively inhibitory neurons persisted in the otherwise granule-cell-depleted area. The data show that interruption of the excitatory trisynaptic pathway from the entorhinal cortex to the CA1 at the level of the dentate gyrus affects hippocampal glucose utilization irreversibly and uniformly. Since some inhibitory neurons seem to survive the ibotenic acid lesion, we suggest that the reductions of hippocampal glucose utilization reflect an imbalance in favor of inhibitory neurons in the ipsilateral hippocampus after the lesion, which manifests also in the contralateral hemisphere via the commissural pathways.

Animals↗

Area specific functional activity in organotypic hippocampal slice cultures. A 2-deoxyglucose study.

Slices of hippocampus from 5 day old rats were cultured by the roller-tube technique. After 4 weeks [14C]-2-deoxyglucose (2-DG) was added to the medium for 45 min, whereafter the cultures were frozen and cut on a cryostat. The sections were thawed onto coverslips and processed for autoradiography. Image analysis of the resulting autoradiographs showed a higher uptake of 2-DG in CA3 than in CA1 and fascia dentata, whereas CA1 and fascia dentata did not differ significantly with respect to 2-DG uptake. The study demonstrates, that organotypic hippocampal slice cultures display an area specific glucose utilization, and thus functional activity, which is similar to that observed in adult conscious rats. We therefore anticipate that the method can be used to examine the integrated activity of the whole neuronal network in these cultures under various manipulations, like hypoxia or additions of various drugs.

Animals↗

Chronic infusion of nerve growth factor does not rescue pyramidal cells after transient forebrain ischemia in the rat.

Male Wistar rats received chronic intracerebroventricular infusions of nerve growth factor (NGF) starting immediately before induction of a transient forebrain ischemia and continuing until 7 days after the infarct. Ischemia was induced by carotid occlusion and simultaneous hypotension. Seven days after the infarct the brains were examined histologically and the number of necrotic cells in the hippocampus were counted. The results did not reveal any difference in treated vs. untreated animals. The data suggest that application of exogenous NGF does not prevent ischemic cell death in the hippocampus.

Animals↗

Plasticity in the rat hippocampal formation following ibotenic acid lesion of the septal region: a quantitative [14C]deoxyglucose and acetylcholinesterase study.

The local cerebral glucose utilization was measured in the hippocampal formation 3, 21, and 90 days after bilateral lesions of the medial septal nucleus and the nucleus of the diagonal band of Broca by multiple ibotenic acid injections. The CMRglc was determined in hippocampal areas and layers and various limbic and visual regions by quantitative [14C]2-deoxyglucose autoradiography using a computerized image-processing system. Three days after lesion, CMRglc was significantly decreased in 26 of the 38 structures examined. The most pronounced reductions were found in CA2 and CA3, the subiculum, and the parasubiculum. The CMRglc values of the 21- and 90-day postlesion groups did not differ significantly from control data when univariate statistics were used. However, by means of a factor analysis and subsequently a discriminant analysis as a multivariate test for group differences, significant lesion-induced CMRglc changes could be detected between the control group, the 3-day group, and the 90-day group. The 21-day group did not differ significantly from the controls. The data indicate that 90 days after lesion of the medial septum/diagonal band complex (MSDB), a considerable recovery of the mean CMRglc was found in the hippocampal region, although a normal level was not reached. In a parallel series, processing of sections for acetylcholinesterase (AChE) histochemistry revealed a severe destruction of AChE-positive fibers in the hippocampus at 3 days after lesion and a conspicuous recovery in the amount of stainable fibers and their staining intensity at 21 days postlesion. In the 90-day group, the AChE fibers recovered even further but did not reach the values of unlesioned sham-operated controls. The present study indicates that sprouting of surviving cholinergic afferents might be an important morphological substrate for CMRglc recovery in the hippocampus after MSDB lesion.

Acetylcholinesterase↗

Volumes of the cytoarchitectonic areas in the rat cerebral cortex.

The volumes of the isocortical, periallocortical and allocortical areas were measured in the brains of nine 6 month old male Wistar rats. After perfusion fixation with Bodian's solution, determination of brain weight, paraffin embedding and serial sectioning, the areal volumes were estimated with the Cavalieri method and corrected for individual brain shrinkage. Thus, fresh volumes were measured. The present report provides comprehensive data on the volumes of the cortical areas of one hemisphere in normal adult rats and can be used as a reference for allometric and experimental studies.

Animals↗

Local cerebral glucose utilization in the brain of old, learning impaired rats.

The local cerebral glucose utilization (LCGU) was measured in 63 different cortical areas and nuclei of the telencephalon, diencephalon and rhombencephalon of young adult (3 to 4-month-old) rats and of 27-month-old Wistar rats, in which learning impairments had been proven by a water maze test. The LCGU was determined by [14C]2-deoxyglucose autoradiography. In the old rats the mean LCGU of all brain regions was significantly reduced by about 10% compared with the young control group; the mean LCGU was 74.2 mumol glucose/(100 g x min) in the young and 66.7 in the old rats. Different degrees of LCGU decrease were found in the different regions. Most of the brain regions with significantly reduced LCGU values in the aged, learning impaired rats were associated with auditory and visual functions, the dopaminergic system, and structures known to be involved in learning and memory processes. Therefore, the regional pattern of LCGU reduction found in the aged, learning impaired rats did not resemble any known pattern found after lesions of a single transmitter system or systemic administration of transmitter agonists or antagonists.

Aging↗

Ultrastructure of axons in stereotaxically placed ibotenic acid-induced lesions of the hippocampus in the adult rat. Evidence for demyelination and degeneration of dispersed axons of passage.

The fate of axons in lesions following stereotaxic injections of ibotenic acid into the rat hippocampus was studied on the ultrastructural level. Myelinated and unmyelinated axons were examined in the, presumably, axon sparing lesions induced by circumscribed in vivo injections of ibotenic acid. In lesions placed in the dentate gyrus or parts of the Ammon's horn a considerable amount of dispersed myelinated axons of passage were affected, showing a characteristic pattern of demyelination and suggesting the involvement of oligodendroglia processes. However, the structural integrity of unmyelinated axons of passage, studied with the example of the mossy fiber system, was completely unaffected after exposure to ibotenic acid. Thus, at least in the hippocampus, in situ injections of ibotenic acid cannot be looked upon as being completely axon sparing as frequently proposed.

Animals↗

Differential vulnerability of neurons toward local injection of ibotenic acid in the hippocampus of the adult rat. An electron microscopic study.

The ultrastructural changes of neurons following in situ injection of biotenic acid into the adult rat hippocampus were investigated. Independent from the localization of the injection site, swelling and subsequent vacuolar degeneration was seen in the center of the induced lesion, in the periphery the nerve cells degenerated electrondense and shrunk. In the center of the lesion all perikarya degenerated, whereas a considerable amount of different hippocampal interneurons survived in the lesion's periphery. Furthermore, the extent of the lesion sites suggested that CA1 pyramids were more sensitive than CA3 perikarya and the granule cells of the dentate gyrus. The different vulnerability of the various hippocampal neurons to the in situ exposure of ibotenic acid can tentatively be interpreted by their differing receptor equipment.

Animals↗

Postischemic glucose utilization in rat hippocampal layers.

The influence on hippocampal glucose utilization was determined in male Wistar rats 7 days after a 10-min forebrain ischemia. Ischemia was induced by clamping of the carotid arteries and lowering blood pressure to 40 mm Hg. Despite severe neuronal damage as assessed by histological techniques, local cerebral glucose utilization (LCGU) was significantly increased in the pyramidal and radiatum layer of the CA1 sector, while in layers of the CA2, CA3 and CA4 sector and dentate gyrus. LCGU was reduced compared to non-ischemic controls. The increases in LCGU are suggested to reflect long-lasting hyperexcitation in the selectively vulnerable CA1 sector, implicating a correlation between cellular hypermetabolism and neuronal damage.

Animals↗

Local cerebral glucose utilization in the neocortical areas of the rat brain.

The neocortex of the rat brain can be subdivided into regions of different local cerebral glucose utilization (LCGU). However, only a few neocortical areas can be delineated by differences in mean LCGUs between neighbouring areas. These area borders correspond exactly with cytoarchitectonically defined borders found in adjacent Nissl-stained preparations. On the other hand, nearly all of the architectonically defined area borders are also recognizable in the LCGU pictures, if differences in laminar distribution patterns of LCGU are taken into account. Furthermore, interareal differences in mean LCGU mainly reflect changes in layer IV, whereas layers II-III and V-VI show nearly identical LCGU values in all neocortical areas of the rat brain. The primary sensory areas exhibit the highest LCGU in layer IV, while the primary motor cortex shows a high LCGU in layer V. As the cytoarchitectonically defined pattern of the cortex is generally corroborated by the regional and laminar LCGU distribution, anatomical, metabolic and functional aspects of cortical architecture are associated.

Animals↗

Glucose utilization in rat hippocampus after long-term recovery from ischemia.

The influence on hippocampal glucose utilization of a transient 10-min forebrain ischemia was quantified in male Wistar rats after 2 and 3 weeks as well as after 3 months by application of the [14C]2-deoxyglucose technique. Ischemia was induced by occlusion of the carotid arteries and simultaneous lowering of the blood pressure to 40 mm Hg. For identification of the hippocampal architecture, sections were stained for perikarya (cresyl violet) and for acetylcholinesterase. The hippocampal regions clearly showed different responses to the ischemic insult. The necrotic pyramidal cells being almost completely removed, significant increases in glucose utilization occurred in most layers of the CA1 sector at 2 and 3 weeks post ischemia, while widespread reductions prevailed in all other sectors and the dentate gyrus. At 3 months after the ischemic insult, glucose utilization was reduced in all hippocampal structures including the CA1 region. The increases in glucose utilization in the CA1 sector are suggested to indicate long-lasting presynaptic hyperexcitation, while the widespread reductions in glucose utilization demonstrate that neuronal activity is also altered in hippocampal areas that do not show major histological damage.

Animals↗

Principles of the 2-deoxyglucose method for the determination of the local cerebral glucose utilization.

Sokoloff and co-workers developed the 2-deoxy-D-[1-14C]glucose (2DG) method in order to study the local cerebral glucose utilization (LCGU) of discrete brain regions in vivo. Energy metabolism of the adult mammalian brain is almost entirely dependent on glucose. The majority of the glucose taken up by the brain is needed for the maintenance of the membrane potentials and the electrical activity. The functional activity could thus be shown to be closely linked to energy metabolism. Consequently, examination of the energy metabolism by measuring the cerebral metabolic rate for glucose can provide information concerning functional activity in all of the neuroanatomically defined regions of the brain. Studying the fate of experimentally injected 2-deoxy-D-[1-14C]glucose, a radioactive labeled analogue of glucose, and, subsequently, employing quantitative autoradiographic techniques, it is possible to estimate the levels of the local cerebral glucose utilization in specific regions of the brain. According to Sokoloff (1982) the LCGU represents a "metabolic encephalography".

Animals↗

Different metabolic changes in the lateral geniculate nucleus and the superior colliculus of adult rats after simultaneous or delayed double enucleation.

By means of the [14C]deoxyglucose method the local cerebral glucose utilization (LCGU) was measured in the lateral geniculate nucleus and the superior colliculus of rats with a simultaneous double enucleation, animals with an enucleation of the right eye between neonatal and adult stages followed by an enucleation of the left eye some months later and adult control rats. The control animals show LCGU values within the limits published by other observers. The LCGU values of the simultaneously double-enucleated rats are reduced on both sides to the same extent by about 20%. The dorsal lateral geniculate nucleus shows the largest decrease. The LCGU values of the rats with the delayed double enucleation have decreased even more (up to 37%). The right sided visual brain regions have a significantly lower LCGU than the corresponding regions on the left side. These findings indicate that unilateral enucleation from neonatal to adult stages leads to adaptive changes resulting in a higher metabolic vulnerability, which is revealed by the second enucleation.

Aging↗

Local cerebral glucose utilization in the hippocampus of old rats.

The local cerebral glucose utilization (LCGU) was measured in the different areas and layers of the Ammon's horn and dentate gyrus of young adult (3 to 4-month-old) rats, and of 27-month-old rats with proven cognitive deficits. The LCGU was determined by quantitative [14C]2-deoxyglucose autoradiography. Compared to young animals, in the old rats the LCGU was significantly reduced by 12% to 15% in the oriens layers of CA1 and CA2, the pyramidal layers of the CA sectors 1-3, the radiatum and lacunosum-molecular layers of CA2 and CA3 and in the lucidum layer of CA3. The LCGU values of all the other layers of the Ammon's horn and the dentate gyrus did not differ significantly between young and old rats. The pattern of the LCGU reduction found in the old rats roughly resembles changes found after fimbra-fornix lesions or systemic administration of scopolamine, suggesting a functionally important deficit in the cholinergic innervation of the old rats' hippocampi.

Aging↗

Local cerebral glucose utilization in the autoimmune New Zealand black (NZB) mouse.

By means of the [14C]-2-deoxyglucose method the local cerebral glucose utilization (LCGU) was measured in 41 brain regions in autoimmune New Zealand Black (NZB) mice and in Carworth Farm Winkelmann (CFW) mice, which served as the control strain. At the age of 6 months, the mean LCGU of all measured areas and brain stem nuclei was 67.7 mumol glucose/(100 g x min) in the nonautoimmune CFW mice. These LCGU values are within the limits published by other observers. In contrast, in the aged-matched NZB mice the glucose use was markedly reduced, the mean LCGU of all measured areas being 37.7 mumol glucose/(100 g x min). These findings suggest that the immunological, morphological and behavioural abnormalities in the aged NZB mouse correlate with a reduced functional activity of the central nervous system, measured as reduced cerebral glucose utilization.

Animals↗

The determination of the local cerebral glucose utilization with the 2-deoxyglucose method.

In the adult mammalian brain, the energy metabolism is almost entirely dependent on glucose. Furthermore, a close relationship between the energy metabolism and the functional activity could be shown. Thus, the functional activity of the brain or parts thereof can be quantified by measuring the cerebral metabolic rate for glucose. Studying in vivo the fate of a radioactive labeled analogue of glucose, the 2-deoxy-D-[1-14C]glucose, and using quantitative autoradiographic techniques, it is possible to estimate the cerebral glucose utilization of every discrete brain region. The advantage of the 2-deoxyglucose method is, that the local cerebral glucose utilization represents a "metabolic encephalography" (Sokoloff 1982).

Animals↗

Local cerebral glucose utilization in the Ammon's horn and dentate gyrus of the rat brain.

The local cerebral glucose utilization (LCGU) was measured in different regions and layers of the Ammon's horn and dentate gyrus in the conscious rat. The LCGU was determined by quantitative [14C]2-deoxyglucose autoradiography using a computerized image processing system. In the hippocampus, the various regions and layers exhibited different glucose consumptions, the lowest values being found in the alveus and the highest ones in the lacunosum-molecular layers of the sectors of the Ammon's horn and the molecular layer of the dentate gyrus' external limb. Additionally, in many layers, the LCGU values of the left hemispheres were found to be higher compared with the right hemispheres. The analysis of LCGU changes in rostrocaudal direction revealed, that in sector 1 of Ammon's horn and in the dentate gyrus the glucose consumption decreased from rostral to caudal levels, whereas in sector 3 of Ammon's horn an increase was found.

Afferent Pathways↗

Effect of the 5-HT1A receptor agonist ipsapirone on the local cerebral glucose utilization of the rat hippocampus.

Local cerebral glucose utilization (LCGU) was measured in the hippocampus of the rat brain following i.p. injection of the anxiolytic drug and 5-HT1A receptor agonist ipsapirone (TVX Q 7821). Administration of ipsapirone (5 mg/kg) reduced glucose utilization in the various hippocampal areas to variable extent. The most subtle reduction took place in the dorsal subiculum, while the most pronounced decrease was found in sector CA4 of Ammon's horn. The degree of LCGU reduction can be related to the 5-HT1A receptor density in the respective areas.

Animals↗