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Biomedical subjects

B Will

Publications and source records attributed to B Will.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Diagnostic and therapeutic measures in craniocerebral trauma in the intensive care unit].

Diagnostic and therapeutic measures after severe head-injury in the intensive care unit are discussed. The main goal of all efforts consists in minimizing secondary brain damage. Adequate shock therapy in the initial phase proves crucial for the later outcome. Methods and indications of intracranial pressure monitoring are described. Electrophysiological tests, transcranial doppler sonography, EEG and serial CCT controls provide valuable additional information. Frequent clinical assessments however remain the golden standard despite all technical advances. Surgical and conservative modalities of therapy are further examined. Controversial methods (barbiturates, steroids, some osmotic active agents) as well as new concepts of therapy are also included. The clinician is provided with a critical discussion of the value of the different methods from our point of experience.

Brain Damage, Chronic↗
PubMed1994

Morphological and behavioural effects of granule cell degeneration induced by intrahippocampal fluid injections in intact and fimbria-fornix lesioned rats.

This study was aimed at determining whether granule cell degeneration induced by intragyral injections of a neutral fluid (0.9% NaCl with 0.6% glucose, pH 7.0, 2 sites per hippocampus, 2 microliters/site, 1 microliter/min) produced behavioural deficits in rats which, 2 weeks prior to the injections had received either fimbria-fornix lesions or sham-operations. In both sham-operated and lesioned rats, we found such injections to induce a comparable, topographically-limited loss of granule cells in the dorsal leaf of the dentate gyrus and, in the close vicinity of the degeneration area, a severe shrinkage of the molecular layer with concomitant morphological reorganizations (e.g. acetylcholinesterase reaction products were distributed uniformly throughout the molecular layers of sham-operated rats). While the fimbria-fornix lesions produced classically reported behavioural deficits (hyperactivity in both a familiar and an unfamiliar environment. reduced T-maze alternation rates and impaired radial-maze performance), we could not detect adversive effects of the granule cell degeneration on either of these variables in sham-operated and lesioned rats. Our data suggest that limited granule cell degeneration induced by intragyral fluid injections has no effect on locomotor activity, spontaneous alternation and spatial learning. Therefore, we may also infer that the granule cell damage observed after an intragyral implantation of a fetal neural cell suspension does probably not account for the behavioural deficits which, in some experiments, have been found in fimbria-fornix lesioned rats bearing intragyral cell suspension grafts.

Animals↗
PubMed1994

"Short-stops" in rats with fimbria-fornix lesions: evidence for change in the mobility gradient.

Rats with damage to the hippocampal formation and allied structures are hyperactive in many test situations but the cause of this hyperactivity is not known. Here the activity of control rats and rats with fimbria-fornix lesions is documented in tests of overnight activity. Details of activity are then characterized from video recordings of behavior in an open field. Rats with fimbria-fornix lesions make significantly more stops of shorter duration and thus more individual trips than control rats but they do not differ in the distance traveled on individual trips or in travel speed. It is suggested that the main difference between fimbria-fornix rats and control rats is that when fimbria-fornix rats stop they remain "still" for shorter durations than do control rats. This finding is discussed in relation to a theory of locomotor/exploratory behavior, and in relation to its implications with respect to the performance of fimbria-fornix rats in studies of learning and memory.

Animals↗
PubMed1994

The effects of intrahippocampal raphe and/or septal grafts in rats with fimbria-fornix lesions depend on the origin of the grafted tissue and the behavioural task used.

Long-Evans female rats sustained electrolytic lesions of the fimbria and the dorsal fornix and, two weeks later, received intrahippocampal suspension grafts of fetal tissue. The grafts were prepared from regions including either the medial septum and the diagonal band of Broca (septal grafts), or the mesencephalic raphe (raphe grafts), or from both these regions together (co-grafts). All rats were submitted to a series of behavioural tests (home cage and open-field locomotion, spontaneous alternation, radial-arm maze and Morris water maze performance) run over two periods after grafting (one to nine weeks and 20-35 weeks). Two weeks after completion of behavioural testing, histological (acetylcholinesterase and Cresyl Violet staining) and/or neurochemical (choline acetyltransferase activity, high-affinity synaptosomal uptake of choline and serotonin, noradrenaline, serotonin and 5-hydroxyindolacetic acid concentrations) verifications were performed on the hippocampus. Compared to sham-operated rats, lesion-only rats exhibited hyperactivity which was transient in a familiar environment (home cage) and lasting in an unfamiliar one (open field), decreased rates of spontaneous T-maze alternation, and impaired memory performance in both the radial-arm maze and the Morris water maze. These rats also showed decreased cholinergic and serotonergic markers with a maximal depletion in the septal two-thirds of the hippocampus. Noradrenaline concentration tended to be increased in the dorsal third of the hippocampus, but was not modified in the other two-thirds. While septal grafts specifically increased the cholinergic markers and raphe grafts the serotonergic ones, neither of these grafts produced a lasting effect on any behavioural variable. Conversely, the co-grafts, which increased both the cholinergic and serotonergic markers in the septal two-thirds of the hippocampus, completely normalized the Morris water maze probe trial performance, but failed to affect any of the other behavioural variables. Our present results confirm that grafts of fetal neurons injected into the denervated hippocampus may induce a neurochemical recovery that depends on the anatomical origin of the grafted cells, and that co-grafting two fetal brain regions allows the combination of their individual neurochemical properties. Furthermore, our results show that these neurochemical effects of the co-grafts may be involved in the recovery of behavioural function observed in the water maze. However, somewhat paradoxically, those effects appear inefficient for inducing any recovery in other behavioural tasks, even in the radial-arm maze; which is assumed to measure similar spatial functions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Hippocampal amino acid concentrations after raphe and/or septal cell suspension grafts in rats with fimbria-fornix lesions.

Two weeks after infracallosal electrolytic fimbria-fornix lesions, Long-Evans female rats received intrahippocampal suspension grafts of either fetal septal or mesencephalic raphe tissue, or a mixture of both. Ten months after lesion surgery, the concentrations of alanine, aspartate, GABA, glutamate, glutamine, glycine, serine and taurine were determined in a dorsal, a "middle" and a ventral region of the hippocampus. We found neither the lesions nor the grafts to have significantly modified the concentration of these amino acids which, in all groups, presented a regional heterogeneity in their hippocampal distribution. GABA, glutamate and glutamine were highest in the ventral hippocampus, whereas the other amino acids were highest in the dorsal region. Our results (i) show that fimbria-fornix lesions do not result in lasting effects on hippocampal concentrations of the assessed amino acids, (ii) confirm the regional heterogeneity in the distribution of these amino acids in the hippocampus and (iii) demonstrate that cell suspension grafts of fetal septal or mesencephalic raphe tissue, as well as grafts of a mixture of both of these tissues, do not exert a non-specific effect on either of the amino acid concentrations measured. These data complete those of the preceeding paper [Kiss et al. (1990) Neuroscience 36, 61-72] concerning the effects of the same grafts on hippocampal cholinergic, serotonergic and noradrenergic markers, as well as on several behavioural variables.

Amino Acids↗
PubMed1994

Lesions of supracallosal or infracallosal hippocampal pathways in the rat: behavioral, neurochemical, and histochemical effects.

Long-term behavioral and neurochemical effects of bilateral lesions to only the infracallosal component of the "so-called" septohippocampal pathways (cingular bundle, fimbria and fornix) have not been assessed. This experiment compared the behavioral, histochemical and neurochemical effects of supracallosal (SUPRA; cingular bundle) and infracallosal (INFRA; fimbria-fornix) hippocampal denervations in Long-Evans female rats. The rats were tested, over two periods (8-52 and 92-170 days postlesion), for open field locomotion, spontaneous alternation and radial-maze performance. Subsequently, histochemical or neurochemical determinations of cholinergic, serotonergic and noradrenergic hippocampal innervations were performed using acetylcholinesterase-staining, determination of high-affinity synaptosomal uptake of choline and serotonin, and measurement of hippocampal serotonin and noradrenaline concentrations by HPLC methods. Whatever behavioral test was considered, no significant effect was found in rats with SUPRA lesions, whereas rats with INFRA lesions were permanently impaired in all tests. Histochemical and neurochemical analyses showed hippocampal cholinergic as well as serotonergic markers to be substantially decreased in INFRA rats as compared to SHAM and SUPRA rats. The SUPRA rats exhibited a weak but significant reduction of both serotonergic and noradrenergic markers compared to SHAM and INFRA rats. These results suggest that lesions limited to the infracallosal pathway induce a hippocampal denervation sufficient to account for most of the behavioral, histochemical and neurochemical deficits classically reported following extensive lesions of the anterior hippocampal connections. Since the behavioral and neurochemical deficits were found to be lasting, it is suggested that bilateral infracallosal damage to the septohippocampal pathways might constitute an interesting paradigm of partial hippocampal deafferentation to investigate the effects of neural grafts or other treatments in an animal model of Alzheimer's disease.

Acetylcholinesterase↗
PubMed1993

Functional consequences of a single nerve growth factor administration following septal damage in rats.

This study examined how possible nerve growth factor (NGF)-induced behaviour changes after septal damage might be modulated by the lesion extent, the dose of NGF administered and the delay between surgery and the onset of testing. In a first experiment, young rats which received electrolytic septal lesions of high or low intensity (inducing respectively large and mild lesions) were treated with 10 or 30 micrograms NGF administered intrahippocampally in a single injection. They were tested 4 months postoperatively for open field ambulation, spontaneous alternation and radial maze performance. It was observed that irrespective of the severity of the lesions rats were impaired in the spontaneous alternation and radial maze tests; however, no obvious changes appeared in the open field test. While an NGF injection did not affect behavioural performances in rats with large lesions, it was capable of ameliorating behavioural deficits in the spontaneous alternation and radial maze tests of rats with mild lesions in both NGF dosage groups. It was also seen that lesions produced a general decrease in hippocampal choline acetyltransferase (ChAT) activity, which was not significantly affected by an NGF administration. There was no significant correlation between ChAT activity and behavioural performance of NGF-treated rats. In a second experiment, young rats received mild septal lesions and were treated with 10 micrograms NGF. These rats were tested 2 weeks postoperatively for radial maze performance. NGF rats exhibited similar behaviour to controls with regard to all of the variables measured. The present results suggest that a single NGF administration spares some abilities to use spatial information efficiently providing lesions are partial.

Animals↗
PubMed1993

Injections of fluid or septal cell suspension grafts into the dentate gyrus of rats induce granule cell degeneration.

This study was originally aimed at investigating the effects of intragyral cell suspension grafts which had been enriched in basic fibroblast growth factor (bFGF) before being implanted into the rat hippocampus denervated by aspiration of the septohippocampal pathways. Whether treated with vehicle alone, vehicle + bFGF, cell suspension with or without bFGF, and irrespective of the surgical treatment (sham-operation, lesions or lesions + grafts), we unexpectedly found approximately 80% of the rats to show morphological alterations in the dentate gyrus (20 weeks post-grafting). These alterations consisted of loss of a part of the granule cells; this loss was most often located in the dorsal leaf of the dentate gyrus. Also, in the close vicinity of the degeneration area, we found severe shrinkage of the molecular layer and disappearance of the typical laminae pattern of acetylcholinesterase distribution. These observations confirm previous findings which showed that fluid injections into the dentate gyrus, a widely used technique for intracerebral administration of drugs, trophic factors or neural grafts, may induce undesirable granule cell necrosis.

Animals↗
PubMed1993

[Subacute and chronic epidural hematoma after craniocerebral trauma].

During an 8-year period, fifteen patients with subacute or chronic epidural haematoma were seen among 110 treated cases of extradural haematoma corresponding to a frequency of 13.6%. Increasing headache, nausea, vomiting, mild drowsiness and cranial nerve palsy were the symptoms resulting in the correct diagnosis in most cases. Clinical and pathological findings are described, and the factors influencing the course of events are discussed. The most important factors are cerebral atrophy, age, source of bleeding and location. By means of early CT (computed tomography) diagnosis of haematoma, fatal outcome could be prevented in most of the cases.

Adolescent↗
PubMed1992

Nerve growth factor and septal grafts: a study of behavioral recovery following partial damage to the septum in rats.

Previous studies have produced conflicting results about the effects of intracerebral injection of NGF after septal damage in rats: in one experiment, behavioral deficits in maze tasks were exacerbated by NGF administration whereas they were alleviated in another one. The present investigation aimed to clarify the effects of NGF and to identify factors liable to induce different behavioral outcomes. Behavioral effects were assessed following a postsurgical delay of five months using various parameters: food consumption in a novel environment, spontaneous activity, locomotion in an open-field, immobility in a tail suspension test, spontaneous alternation in a T-maze and performance in a radial eight-arm maze. Possible influence of intrahippocampal sympathetic fiber ingrowth occurring after septal lesions was ruled out, as the comparison of rats subjected to superior cervical ganglia removal with their lesion-control counterparts showed few behavioral differences, even after NGF administration. All lesioned rats showed reduced adaptability in most of these tests. Grafts partially reversed the lesion-induced deficit in spontaneous alternation. A single intracerebral NGF injection was found to ameliorate radial maze performance, whether rats were grafted or not. However, it appeared that the number of strategies available to NGF-rats in the radial maze task was as limited as for lesion-control rats. These findings suggest that NGF-rats do not recover spatial abilities lost after septal lesions, but are able to make more efficient use of remaining capacities to master the maze task.

Animals↗
PubMed1992

Chronic infusion of GABA into the nucleus basalis magnocellularis or frontal cortex of rats: a behavioral and histological study.

In order to determine the influence of the nucleus basalis magnocellularis (NBM) on the sensorimotor function of the frontal cortex (FCx) of the rat, GABA at various concentrations (10, 50 or 100 micrograms.microliters-1) was administered into these structures. GABA was infused for four consecutive days after which saline was infused for another four. On the contralateral side the order of administration was reversed. Each structure received GABA while its homologous on the contralateral side received saline. Before, during and after drug infusion, the animals were weighted and their performance in two non-reinforced behavioral tasks (beam walking and spontaneous rotation) was examined. When GABA was infused into the FCx, a dose-dependent and reversible sensorimotor deficit was observed along with a behavioral withdrawal syndrome upon GABA discontinuation. When GABA was administered into the NBM, a reversible sensorimotor deficit was observed only when GABA was infused at the highest concentration. In this case no behavioral changes were observed upon GABA discontinuation. Histologically, a gliosis was observed in the NBM in which GABA was infused at the two highest concentrations without saline pretreatment; these effects were not observed when GABA was infused without saline pretreatment into the FCx. In relation to our previous findings, these results suggest that i) the FCx is directly involved in the expression of sensorimotor functions, while the influence of the NBM on these functions appears only after severe subcortical damage, ii) a GABA withdrawal syndrome is observed following GABA administration in the FCx but not in the NBM, and iii) "tonic" effects of GABA are dose-related and partially dependent upon pretreatment conditions and the brain region infused.

Analysis of Variance↗
PubMed1992

Local cerebral glucose utilization during chronic infusion of GABA into the nucleus basalis magnocellularis of rats.

The metabolic effects of gamma aminobutyric acid (GABA) unilaterally infused for 24 h into the nucleus basalis magnocellularis (NBM) of rats were studied using the 2-deoxyglucose method for measuring local cerebral metabolic rates for glucose (CMRglc). These results demonstrated that GABA infusion at the concentration of 100 micrograms.microliters-1 induced a strong ipsilateral depression in glucose utilization in the NBM and in some surrounding structures (e.g., the lateral hypothalamic area, thalamus, and amygdala) as well as in the major cortical targets of NBM neurons (i.e., the frontal, parietal, and temporal cortices). On an other hand, GABA infusion at the concentration of 10 micrograms.microliter-1 had no significant effect on cerebral metabolism compared to the saline-infused rats. Nevertheless, both GABA at the concentration of 10 micrograms.microliter-1 and saline induced a reduction of cerebral metabolism in the infused NBM, compared to the contralateral noninfused NBM. It was also demonstrated that saline pretreatment reduced the metabolic depression induced by GABA infusion at the highest concentration. When GABA was infused at the concentration of 100 micrograms.microliter-1, a slight reduction of CMRglc was observed in the hemisphere contralateral to the infused one, mainly in NBM target areas. In view of our previous behavioral data, these results suggest among others, that there is no necessary relationship between cerebral glucose metabolism and behavioral expression.

Animals↗
PubMed1992

Cytophotometric analysis of magnocellular azure B-RNA and Feulgen-DNA following chronic GABA infusion into the nucleus basalis of rats.

This investigation was undertaken to examine possible cytopathic effects of GABA infusion on nucleus basalis (NBM) magnocellular neurons. Sixty-three male Long-Evans rats received unilateral, intra-NBM infusions of either GABA100 (100 micrograms/microliters/h), GABA10 (10 micrograms/microliters/h), or ultrafiltered saline (1 microliter/h) for a period of 24 hours. Rats from each of these groups were sacrificed at either 24 hours, 48 hours or 8 days following initiation of infusions. The sham operated hemisphere of each rat served as a control for the infused hemisphere. After stoichiometric azure B-RNA and Feulgen-DNA staining of brain sections, scanning-integrating microdensitometry was used to quantify GABA-induced alterations in these well established indices of neuronal toxicity. These results provide evidence that the neurotoxic effects of 24 hours of 100 micrograms/microliters-h GABA infusion are manifested within 48 hours post-initiation of infusions. Although 24 hours of 10 micrograms/microliters-h GABA infusion suppressed NBM neuronal metabolism, the lower magnitude and duration of this effect signified an impending recovery. GABA infusion resulted in little if any NBM neuronal chromatin template impairment (i.e., reduced Feulgen-DNA reactivity), irrespective of the dosage employed and the delay prior to sacrifice.

Analysis of Variance↗
PubMed1991

Long term effects of septohippocampal lesions and intrahippocampal grafts on acetylcholine concentration, muscarinic stimulated formation of inositol phospholipids and electrically evoked release of neurotransmitters in the rat hippocampus.

Long Evans female rats sustained aspirative lesions of the septohippocampal pathways; subsequently, they received intrahippocampal suspension grafts of fetal septal-diagonal band or hippocampal tissue. The long term (8-10 months post-surgery) effects of these treatments were examined in the hippocampus for the following variables: concentration of hippocampal acetylcholine (ACh), muscarinic-stimulated (carbachol) formation of inositol monophosphate, accumulation of tritiated choline, noradrenaline (3H-NA) and serotonin (3H-5-HT), electrically evoked release of 3H-acetylcholine (3H-ACh), 3H-NA and 3H-5-HT, and choline acetyltransferase (ChAT) activity. The lesions decreased the levels of endogenous ACh, the accumulation of 3H-choline and 3H-5-HT and the evoked release of both 3H-ACh and 3H-5-HT as well as the ChAT activity, but they failed to significantly affect the muscarinic-stimulated formation of inositol monophosphate and the accumulation and release of 3H-NA. Grafts of hippocampal cells were found to be ineffective on all lesion-induced effects. In contrast, grafts of septal-diagonal band origin attenuated the deficit of hippocampal concentrations of ACh and accumulation of 3H-choline without, however, improving release of 3H-ACh, accumulation and release of 3H-5-HT, and ChAT activity. These observations suggest that: (i) denervation-induced hippocampal muscarinic supersensitivity might not be long-lasting or the lesions, which in some cases spared the lateral edges of the fimbria, failed to induce any muscarinic supersensitivity, (ii) intrahippocampal grafts rich in cholinergic neurons do not foster recovery from the lesion-induced noncholinergic deficits we assessed, (iii) recovery of function may be expressed by some but not all biochemical or pharmacological cholinergic variables and (iv) graft-derived hippocampal reinnervation may be less efficient than the endogenous innervation of intact rats as indicated by the restoration of only some of the variables related to cholinergic function by intrahippocampal septal-diagonal band grafts.

Acetylcholine↗
PubMed1991

Graft-induced behavioral recovery from subcallosal septohippocampal damage in rats depends on maturity stage of donor tissue.

Long-Evans female rats sustained electrolytic lesions of the fimbria and the dorsal fornix and, 10-14 days later, received intrahippocampal suspension grafts of septal-diagonal band tissue from either 14-day-old (Group S14, n = 8) or 16-day-old fetuses (Group S16, n = 10), or of parietal cortex from 16-day-old fetuses (Group Cx, n = 10). Sham-operated (Group S, n = 10) and lesion-only (Group Fifo, n = 21) rats served as non-grafted controls. Spontaneous alternation was assessed in a T-maze at three weeks and two months post-grafting. Home cage and open field activity as well as radial maze learning were assessed from two months post-grafting onwards. Fimbria-fornix lesions induced lasting hyperactivity in both the open field and the home cage, impaired radial maze learning and transiently reduced spontaneous alternation rates. Neither type of graft significantly affected home cage activity. Septal-diagonal band grafts improved open field habituation (within trial decline of ambulatory activity) and radial maze learning; the former was observed only in S16 rats, whereas the latter was observed only in S14 rats. Acetylcholinesterase histochemistry revealed an initial lesion-induced depletion of hippocampal acetylcholinesterase (eight days post-surgery) which was no longer observed at the end of the experiment. Acetylcholinesterase positivity was similar in S14 and S16 grafts, which also contained many choline acetyltransferase-positive neurons. Cortical grafts were found to be almost devoid of acetylcholinesterase positivity and no well-stained choline acetyltransferase-positive neurons could be identified. Septal-diagonal band grafts from 14-day-old fetuses and cortical grafts contained more parvalbumin-positive neurons than septal-diagonal band grafts provided by 16-day-old fetuses. These results suggest that grafts rich in cholinergic neurons may promote behavioral recovery from fimbria-fornix lesion-induced deficits. However, such a recovery may concern different behavioral deficits as a function of the age of the implanted tissue, suggesting that the maturity stage of the donor may critically influence the functional expression in the lesioned recipient. Also, such a recovery does not appear to be related solely to cholinergic hippocampal (re)innervation and might depend on the presence, not only of cholinergic neurons, but also of non-cholinergic neuronal populations, such as parvalbumin-positive (probably GABAergic) neurons.

Acetylcholinesterase↗
PubMed1991

The clinical features and prognosis of pseudoseizures diagnosed using video-EEG telemetry.

A total of 110 patients underwent diagnostic evaluation for attacks of uncertain origin by means of video-EEG telemetry and had a diagnosis of pseudoseizures confirmed. Eighty-six patients (78%) were female, mean age of onset 25 years, and mean duration of attacks was 3 years. Many of the patients had erroneously been thought to be suffering from epilepsy. The attacks could be divided into two broad categories: attacks of collapse (one-third) and attacks with prominent motor activity (two-thirds). In some patients, the attacks were associated with incontinence and injury. The differential diagnosis and clinical features of the attacks are described. Additional psychiatric features were present in 52 (47%) patients. Follow-up (for a median 5 years; range, 1 to 14 years) showed that 40% of these patients stopped having pseudoseizures. This favorable outcome was associated with being female, leading an independent life, a formal psychological approach to therapy and counseling, and the absence of coexisting epilepsy, but not with the duration of pseudoepilepsy, prior episodes of pseudostatus, the coexistence of overt psychiatric disease, or the clinical features of the attacks.

Adult↗
PubMed1990

Chronic infusion of GABA and saline into the nucleus basalis magnocellularis of rats: II. Cognitive impairments.

In order to assess sensorimotor and/or cognitive modifications following chronic inhibition of nucleus basalis magnocellularis (NBM) neurons, rats trained in two radial maze paradigms (the classical version of the test and a modified version introducing a one-hour delay between the fourth and the fifth choice) received chronic infusion of gamma-aminobutyric acid (GABA) into the NBM area. GABA (10 and 50 micrograms/microliters/h) was infused for 3 days into the NBM contralateral to their preferred turning direction in the radial maze. Simultaneously, saline (NaCl 0.9%; 1 microliter/h) was infused into the contralateral NBM. GABA and saline infusions were alternated for the subsequent 3-day period. One week later, we investigated the rats' ability to learn a multiple trial passive avoidance task. At the dose of 50 micrograms/microliters, GABA infusion produced (1) a turning bias ipsilateral to the side first infused with GABA, (2) transitory cognitive impairments in radial maze tasks and (3) a deficit in the acquisition of the passive avoidance task. At the dose of 10 micrograms/microliters, the same behavioral deficits were observed except that (1) the turning bias was reversed by the contralateral GABA infusion and (2) cognitive impairments in the radial maze were observed only when a delay was inserted between the fourth and the fifth choice. Histologically, we found a dose-dependent gliosis in the NBM area first infused with GABA. These data suggest a reactivity of the NBM to GABAergic manipulations and the intervention of this structure in both sensorimotor and cognitive processes involved in the radial maze paradigms.

Acetylcholine↗