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Biomedical subjects

B Will

Publications and source records attributed to B Will.

At least 55 records · Page 3Linked to original sources
PubMed1990

Time-dependent effects of intrahippocampal grafts in rats with fimbria-fornix lesions.

Based on three experiments, this study examined whether behavioral and histological effects of fetal septal or hippocampal grafts placed in the denervated hippocampus depend on the duration of post-grafting delays. Each experiment included four groups of rats: sham-operated rats (Sham), rats with aspirative lesions of the fimbria-fornix (Fifo) and rats given both Fifo lesions and intrahippocampal fetal suspension grafts of either septal (Fifo.ST) or hippocampal (Fifo.HT) origin. All rats were tested (i) for home cage activity, (ii) for activity and reactivity in an open field and (iii) for learning ability in a 8-arm radial maze. Except for home cage activity which was also monitored preoperatively, behavioral tests were conducted between 1-2 months postgrafting in Experiment 1 (EXP1), 5-6 months post-grafting in Experiment 2 (EXP2) and 10-11 months post-grafting in Experiment 3 (EXP3). Each test period lasted 3 weeks. Histological controls consisted of acetylcholinesterase (AChE) and cresyl violet staining. Graft size was estimated by computerized image analysis. Normal rats performed well in each experiment. In all experiments, rats with fimbria-fornix lesions showed increased activity in both their familiar (home cage) and unfamiliar (open field) environments, and their performances in the radial maze task were impaired. In no experiment did grafts, whether hippocampal or septal, affect "noncognitive" behavioral variables. However, maze performance was improved by hippocampal grafts in EXP1 (short delay) and by septal grafts in EXP2 (intermediate delay). No graft-induced effect was found in EXP3 (long delay). Concerning AChE-positivity in the dorsal hippocampus, fimbria-fornix lesions reduced staining densities by at least 60%. Both types of grafts were undiscernably AChE-positive, but only septal grafts provided the denervated hippocampus with a significant AChE-positive fiber ingrowth. Differences among groups in density of hippocampal AChE staining were comparable in all three experiments and no correlation between hippocampal AChE-positivity and maze performance was found. Our results suggest that graft-induced recovery from behavioral effects of fimbria-fornix lesions may depend on both the type of tissue implanted (hippocampal vs septal) and the post-grafting delay (1-2, 5-6 and 10-11 months). The recovery observed at a short post-grafting delay with hippocampal grafts and at a longer post-grafting delay with septal grafts was not persistent and concerned only cognitive function as assessed by radial maze performance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Central spinal cord lesions in stenosis of the cervical canal.

34 patients suffering from cervical spondylotic myelopathy confirmed by myelography were examined by delayed CT 6-10 h after myelography. Twelve patients showed bilateral intramedullary collections of contrast medium, predominantly cranial to the stenosis. In these patients males predominated, the duration of clinical symptoms lasted longer although their age was lower. There was no correlation to the degree and the extension of the narrowing of the cervical spinal canal. Half of 20 patients undergoing consecutive decompressive surgery showed intramedullary contrast enhancement, and this was shown again by postoperative MRI in eight. The postoperative clinical and neurophysiological results revealed no change in the majority of patients, but three patients showing intramedullary contrast medium deteriorated in neurophysiological outcome, while only one of the patients in whom intramedullary contrast medium was not noticed got worse.

Adult↗
PubMed1989

Effects of basic fibroblast growth factor (bFGF) on choline acetyltransferase activity and astroglial reaction in adult rats after partial fimbria transection.

Adult rats received a partial and unilateral transection of the fimbria. They received then intracerebroventricular (i.c.v.) injections of 5 microliters of Tris, half of them containing 2.5 ng of basic fibroblast growth factor (bFGF). They were injected twice a week for 4 weeks. At the end of this period, choline acetyltransferase (ChAT) activity was measured in the hippocampus. ChAT activity, which was decreased by the fimbria transection, was higher (by about 20%) in medial hippocampus of the bFGF group compared with the Tris group. In addition, bFGF enhanced the lesion-induced astroglial reaction by changing the morphology of the astrocytes and increasing the apparent number of these reactive astrocytes.

Animals↗
PubMed1988

Housing conditions modulate the effects of intracerebral grafts in rats with brain lesions.

The aim of this study was to examine whether the behavioural effects of intracerebral grafts in rats with brain lesions can be modulated by postoperative housing conditions. Sixty-six young adult female rats were used. Twenty-two rats were sham-operated (S) and 44 rats sustained a complete aspirative lesion (L) of the fimbria-fornix and overlying tissue. The cavity was used in half the rats as the implantation site for solid fetal septal transplants (LT). Two days later, half the rats of each group were housed in an 'enriched' condition (S.EC, L.EC and LT.EC); the other half remained in standard condition (S.SC, L.SC and LT.SC). Two and 10 months later, the rats were tested in a Hebb-Williams maze. Two months after surgery, there was a highly significant lesion effect, no graft effect and no environmental effect except in S rats, S.EC rats making fewer initial errors than S.SC rats. Ten months after surgery, L rats still made more errors than S rats and S.EC rats made fewer initial errors than S.SC rats; however, the lesion-induced deficits were significantly attenuated in LT.EC rats, but not in LT.SC rats. These data show that both the enriched environment and the implant were unable alone to promote behavioural recovery but, applied together, they reduced the lesion-induced deficits. Dorsal hippocampus acetylcholinesterase (AChE)-staining intensity was reduced by the lesions, but this reduction was partially compensated for by the grafts; however, environmental conditions did not affect AChE-staining significantly. This latter observation suggests that the graft-derived partial cholinergic reinnervation of the hippocampus probably does not underly the behavioural improvement observed only in LT.EC rats.

Acetylcholinesterase↗
PubMed1988

Preoperative enrichment and behavioral recovery in rats with septal lesions.

To assess the behavioral effects of preoperative differential housing male rats were placed in either enriched or isolated environments at weaning prior to receiving either sham operations or septal lesions when 57 days of age. Rats with septal lesions showed reduced habituation of ambulation and initially made fewer rears in an empty open field but made more object-contacts coupled with a lack of habituation in the object-filled field. Septal rats also showed severe impairments when tested in a 12-arm radial maze with 7 arms baited and 5 arms unbaited. Preoperative enrichment did not significantly affect these lesion-induced changes. Nevertheless, enrichment significantly lowered ambulation (but did not affect habituation) in the open field and increased the number of manipulatory relative to nonmanipulatory contacts. However, preoperatively enriched septal rats showed a deficit in spontaneous alternation (45%) in contrast to the high levels (83%) shown by intact enriched rats, whereas both intact and septal isolated rats showed similar levels of spontaneous alternation (68%). These results conflict with earlier reports that preoperative enrichment "protects" rats against the deficits produced by septal lesions.

Animals↗
PubMed1987

Effects of postoperative environment on recovery of function after fimbria-fornix transection in the rat.

We have previously found that rats given dorsal hippocampus lesions show reduced deficits on maze learning, spontaneous alternation and extinction tasks when housed postoperatively in an "enriched" as opposed to an "impoverished" environment. In contrast, postoperative enriched conditions were ineffective in rats given bilateral entorhinal cortex lesions. In this study, we examined whether postoperative differential housing would reduce the impairment in radial maze performance induced by fimbria-fornix transections. Significant interactions were found between lesion state and housing condition for the total number of errors made, the number of errors on the first eight arms visited and for the number of arms visited before the first error in an 8-arm maze. The interaction was due to the fact that, in sham-operated rats, isolated ones made more errors than enriched counterparts whereas, in rats with lesions, enriched ones showed no improvement of performance in comparison to isolated counterparts. These data suggest that the integrity of fimbria-fornix pathways is an important factor for the expression of facilitated maze performance in intact enriched rats and in enriched rats with hippocampal system damage.

Animals↗
PubMed1987

Nerve growth factor is a neurotrophic factor for forebrain cholinergic neurons; implications for Alzheimer's disease.

Findings obtained in recent years provide strong evidence that nerve growth factor (NGF) acts as a neurotrophic factor for cholinergic neurons of the mammalian forebrain. NFG receptors are exclusively localized on these neurons in the rat and human forebrain. NGF promotes survival, fiber elongation and expression of transmitter-specific enzymes of forebrain cholinergic neurons, in vivo and in vitro. In adult rats, intraventricular injections of NGF attenuate the degeneration of these cells after experimental lesions. These findings suggest that NGF might be able to attenuate the degeneration of cholinergic neurons occurring in Alzheimer's disease.

Alzheimer Disease↗
PubMed1986

Long-term effects of nerve growth factor and neural transplants on behavior of rats with medial septal lesions.

The present experiment investigated the interaction between exogenous nerve growth factor (NGF) and intrahippocampal septal grafts on the behavior of rats after a medial septum lesion. Young female rats received a bilateral injection of a fetal septal cell suspension into the dorsal hippocampus either immediately (immediate grafts) or 8 days after the lesion (delayed grafts). For delayed grafts, a higher concentration of endogenous neurotrophic factors can be assumed to be present in the deafferentated host tissue at the time of transplantation. One group of rats with lesions received NGF with the immediate grafts, another group received NGF alone. A sham-operated group and 3 groups with lesions (and given either immediate or delayed intrahippocampal saline injections, or no other treatment) constituted controls. The animals were tested for spontaneous alternation and for performance in a radial 8-arm maze, 1, 5 and 9 months postoperatively. Medial septal lesions reduced spontaneous alternation but, 9 months after surgery, recovery was observed in both lesion-control rats and in rats with delayed grafts (but not with immediate grafts). In the radial maze task, lesions produced a persistent impairment, although both immediate and delayed grafts reduced this deficit several months after surgery (more markedly and rapidly in the case of delayed grafts). NGF, however, increased the maze learning deficit especially 5 months postoperatively. These latter results are in contrast to findings of earlier studies showing transient beneficial effects of NGF administration. It is suggested that the effects of NGF in the present study might be due to an enhanced sprouting of sympathetic fibers into the hippocampal formation.

Animals↗
PubMed1986

Unilateral fimbria/fornix lesions attenuate behavioral symptoms induced by subsequent dorsal hippocampal lesions in rats.

Adult rats were given a unilateral fimbria-fornix (5, 10, 15 micrograms colchicine or electrolytic) lesion 30 days before a restricted bilateral dorsal hippocampal lesion to assess the behavioral effects of temporally and structurally spaced lesions. The rats were tested 30 days after the second-stage surgery in the Hebb-Williams maze learning task. All rats with lesions were impaired in comparison with sham-operated control rats. However, those which sustained electrolytic or 5 micrograms colchicine fimbria-fornix lesions before hippocampal lesions were less impaired than rats which received hippocampal lesions alone or hippocampal lesions preceded by fimbria-fornix lesions with larger doses of colchicine.

Acetylcholinesterase↗
PubMed1986

The effects of postoperative physical environment on novelty seeking behaviour and maze learning in rats with hippocampal lesions.

The effects of different postoperative physical environments on novelty seeking and maze learning were tested in rats that sustained dorsal hippocampal lesions at 30 days. After surgery, rats were isolated for one month, either with objects or without objects in their cages. All rats were moved daily to new cages and observed during the first 5 min; during these periods, sham-operated rats and rats with lesions interacted similarly with their environment. At the end of the differential housing period, rats were tested for their reactions towards a novel object introduced to their familiar environment (test 1) and towards a novel environment they were free to explore or to avoid (test 2). In test 1, rats with lesions made more contacts with the novel object than did intact rats, and rats previously housed with objects, whether they sustained lesions or not, climbed on the novel object more often than rats reared without objects. In test 2, rats with lesions made no clear distinction between the novel and familiar environments irrespective of their postoperative treatment; in contrast, intact rats housed with objects differed from intact rats housed without objects in their preference for the novel and familiar environments and in the locomotor activity they displayed in these environments. Following these two tests, learning performance was assessed in an 8-arm radial maze. Rats with lesions made more errors than the intact rats, and within the rats with lesions those reared with objects tended to make fewer errors than those reared without objects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Acetylcholine-rich transplants in the hippocampus: influence of intrinsic growth factors and application of nerve growth factor on choline acetyltransferase activity.

Three groups of rats received either unilateral fimbria-fornix lesions by aspiration through the overlying cingulate cortex (group I), a fimbria-fornix lesion followed by an intrahippocampal transplant of acetylcholine (ACh)-rich embryonic septal tissue (group II), or a similar septal transplant placed into the intact hippocampus, in the absence of the denervating lesion (group III). The 3 groups were subdivided into equal subgroups receiving 6 intrahippocampal injections of nerve growth factor (NGF) at 4-day intervals, control injections of cytochrome c, or no injections. On the 28th day all animals were sacrificed and the majority taken for biochemical analysis of hippocampal choline acetyltransferase (ChAT). The animals with intact hippocampi (group III) were given a denervating fimbria-fornix lesion 3 days prior to sacrifice in order to reveal graft-derived ChAT activity from intrinsic ChAT activity. The fimbria-fornix lesions (group I) depleted hippocampal ChAT activity to 15-20% of normal, which was not influenced by NGF injections. The ACh-rich grafts placed in the denervated hippocampus (group II) restored hippocampal ChAT activity to approximately 60% of the normal level, and this was promoted to approximately 84% of NGF, but not cytochrome c, injections into the hippocampus. Grafts placed into the intact hippocampus (group III) did not raise ChAT activity above the lesion-alone level, and this was not influenced by NGF injections. Acetylcholinesterase (AChE) histochemistry showed no difference in outgrowth from the grafts in the denervated hippocampus with or without NGF injections. The results are interpreted, in agreement with observations in tissue culture, as indicating that NGF enhances ChAT activity in grafted neurons, rather than promoting survival and growth per se.

Animals↗
PubMed1985

Behavioural and neurochemical effects of chronic intraventricular injections of nerve growth factor in adult rats with fimbria lesions.

Rats received bilateral lesions of the fimbria. These lesions impaired their ability to learn a radial maze. Rats given repeated intraventricular injections of nerve growth factor (NGF, 10 micrograms twice weekly during 4 weeks after the lesion) learned the maze problem more rapidly than rats with the same injury but treated with a control protein (cytochrome c). When retested after a period of 6 weeks without NGF treatment, the performance of NGF-treated and cytochrome c-treated rats with fimbria lesions did not differ. Whereas our previous study showed an increase in choline acetyltransferase (ChAT) activity in the septum and the hippocampus 4 days after the last NGF injection, the present study found that after the retest period (i.e. 10 weeks after the last NGF injection) ChAT activity was increased in the septum but not in the hippocampus. The relationship between the NGF-induced changes in ChAT activity and behaviour is discussed.

Animals↗
PubMed1984

Working memory theory of hippocampal function needs qualification.

To compare the predictive value of "cognitive map" and "working memory" theories of hippocampal function, the performance of rats with dorsal hippocampal lesions was compared to that of control rats in a series of experiments. In Experiment I, experimental rats learned a spatial alternation task with normal ease, but in Experiment II, they were significantly impaired on an elevated 8-arm radial maze. In Experiment III, the performance of the same experimental and control rats was compared on two versions of a 16-arm enclosed radial maze. In the first version, carpet inserts served as cues to mark eight unbaited arms and each of the remaining arms contained one food pellet. While both experimental and control rats successfully avoided the set of cued arms, experimental rats reentered uncued baited arms more frequently than did control rats. In the second version no intramaze cues were provided, but the spatial distribution of baited and unbaited arms remained the same as that used in the first version. In this uncued version, experimental rats both entered unbaited arms and reentered baited arms more frequently than did control rats, i.e., they were impaired in both "reference" and "working" memory. These findings are compatible with the hypothesis that hippocampal lesions result in an impaired capacity to form cognitive maps but they are not compatible with the working memory hypothesis. Furthermore, twelve separate evaluators classed experimental rats as using fewer mapping and more orientation strategies than control rats in the 8-arm maze.

Animals↗
PubMed1983

Effects of post-weaning environment and apparatus dimension on spontaneous alternation as a function of phenotype in "dwarf" mice.

The spontaneous alternations of "dwarf" mice estimated in a Y maze proportioned to the size of control mice demonstrated the necessity of reducing the size of the apparatus for testing the "dwarf" mice. Tested in a maze of reduced dimension, the "dwarf" mice showed a significant deficit in this task but only in a T shaped maze, and not in a Y shaped maze. For one month after weaning, "dwarf" and control mice were reared in either an enriched or an impoverished environment. These rearing conditions did not modify the spontaneous alternation of control mice whether estimated in a T or a Y maze, but they significantly altered the behavior of "dwarf" mice, yet only when evaluated in a T maze: "isolated" "dwarf" mice alternating less than "enriched" "dwarf" mice. It is suggested that this behavioral profile displayed by "dwarf" mice in spontaneous alternation might be explained by a deficit in perceiving, integrating and/or utilizing complex spatial information.

Aging↗
PubMed1983

Does post-operative environment attenuate or exacerbate symptoms which follow hippocampal lesions in rats?

Rats with dorsal hippocampal lesions (L) and control rats were tested pre- and post-operatively, on a spontaneous alternation task. Four days after surgery, the L group alternated significantly less than the control group. Starting on the fifth post-operative day, all rats were placed for either 7, 15 or 23 days in one of three different environments: enriched, social or impoverished. Environmental enrichment increased significantly spontaneous alternation in L rats, even for the shortest enrichment period. Although this result might be task and lesion specific, it clearly indicates that post-operative environmental enrichment can help to reduce post-operative symptoms in brain-damaged animals.

Animals↗
PubMed1982

Effects of postoperative environments following dorsal hippocampal lesions on dendritic branching and spines in rat occipital cortex.

Male Long-Evans rats sustained bilateral dorsal hippocampal lesions or were sham-operated when 31 days old. They were reared thereafter in either an 'enriched' (EC) or an 'impoverished' (IC) environment for one month. The effects of lesion and rearing conditions were measured on dendritic branching and spines in layer V pyramidal cells of area 17 by using a concentric ring analysis and by counting the number of spines on 50 micron segments of basilar dendrites. Hippocampal lesions significantly decreased the branching and the number of spines in both EC and IC rats. In contrast to what was observed in most behavioral studies, in which the effects of the postoperative environment were even larger in animals with lesions than in control animals, the present experiment showed that the cytological measures were affected by postoperative rearing conditions only in sham-operated rats (EC greater than IC). It is suggested, therefore, that the morphologic processes underlying the effects of the environment on behavioral recovery after hippocampal lesions can hardly be located in layer V pyramidal cells of area 17, which is considered as one of the most sensitive to environment in intact animals.

Animals↗