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1.
The study was conducted on 48 free-moving male rats to find out the role of the medial preoptic alpha2 receptors in the regulation of sleep and body temperature. Recording electrodes for assessment of sleep-wakefulness, and injector cannulae for injection of drugs in the medial preoptic area were chronically fixed on the skulls of the animals. The noradrenergic fibres projecting to the medial preoptic area were destroyed in 24 rats by administration of 6-hydroxydopamine at the ventral noradrenergic bundle. Though arousal was produced in normal rats by the injection of the alpha2 adrenergic agonist, clonidine, at the medial preoptic area, it induced sedation in rats with noradrenergic fibre lesion. Clonidine did not alter the rectal temperature in normal rats but it induced hypothermia in lesioned rats. Injection of alpha2 antagonist, yohimbine, at the medial preoptic area induced sleep in rats with intact noradrenergic fibres. However, the sleep inducing effect of this drug was very much attenuated in the lesioned animals. There was no significant change in body temperature, in both these groups of animals, after yohimbine administration. The study indicates the role of presynaptic alpha2 adrenergic receptors in arousal response and indirectly supports the contention that the alpha1 postsynaptic receptors at the medial preoptic area are involved in hypnogenesis. It also suggests that the thermal changes induced by adrenergic system are mediated through alpha1 postsynaptic receptors. But the thermal changes do not contribute towards the induced alterations in sleep-wakefulness. It is proposed that there should be separate sets of noradrenergic terminals for regulation of sleep and body temperature.  相似文献   

2.
Previous rodent studies have demonstrated the capacity of cerebellar transplants to organize into trilaminar cell layers typically observed in the normal cerebellum. In Purkinje Cell (PC)-deficient animals, PCs will migrate into the host and form synaptic connections. Recently, fetal cerebellar grafts transplanted into the Purkinje cell degeneration (pcd) mutant mouse were shown to result in an improvement of motor behaviors. These studies indicate the potential therapeutic use of neural transplantation in patients with cerebellar degeneration. In the present study, human fetal cerebellar tissue (8.5 wk postconception) was dissociated and transplanted into the normal cerebellum of nude mice. Six months following transplantation, histological analysis revealed donor cells in recipient mice. Immunostaining for the 28 kDa calcium-binding protein (calbindin) revealed the presence of donor PCs that were organized in discrete cellular layers within the transplant neuropil. In most cases the dendritic processes were oriented in a planar fashion perpendicular to the transplant cell layer. Human neurofilament immunostaining revealed bundles of donor fibers within the core of the transplant and/or at the periphery. These bundles were found to be calbindin positive (PC fibers). Three animals provided evidence of donor PC axon growth ventrally into host white matter, and in one case, this ventral migration reached the deep cerebellar nuclei. Most notable was the development of a pronounced folia-like organization by the implanted cell suspensions. Glial processes within the grafts were aligned perpendicular to the long axis of the transplant folia. These results demonstrate the capacity of human fetal cerebellar cell suspension to reorganize into cell layers typical of the normal cerebellum following transplantation into the rodent cerebellum, and develop an organotypic folia-like organization.  相似文献   

3.
Pulp tissue, enamel and incisal and basal dentine of the mandibular incisor were taken from one litter of rats and transplanted subcutaneously or intracerebrally to sex-matched, 5-day-old animals of the subsequent litter of the same parents. As sham-operations the mere transplantation instrument was inserted into the transplantation sites. With some exceptions, the host animals were killed 4, 32, 128-138 and 210 days after the operation and the transplantation sites were examined either grossly or microscopically or both. The pulp tissue transplantation had resulted in formation of osseous tissue observed 128 days post-operatively. Bone was found in association with many of the basal dentine transplants 128-210 days after their insertion whereas no such tissue was observed with the transplanted enamel of incisal dentine. The sham-operation seemed to have elicited intracerebral bone formation in two animals. The osteoinductive activity of the transplanted tissues seemed reduced by their mineral phase. Further, in contrast to demineralized hard tissues, the non-demineralized inductive agents do not seem to possess bone morphogenetic properties.  相似文献   

4.
One of the most determining factors for the survival of tissue grafts is an intact vasculature. This vasculature must, however, be linked to the circulation of the host animals for survival and growth to occur. The mechanism(s) of revascularization of pancreatic tissue grafts is still unclear and more so the process by which the host blood vessels anastomose with those of the graft. The microvasculature and revascularization of neonatal pancreatic tissue fragments transplanted into the anterior eye chamber of rats were investigated using conventional light and electron microscopy as well as the india ink perfusion method. Light microscopy demonstrated that the blood vessels of the host iris revascularized the transplants within 24 h of transplantation. Sinusoidal blood capillaries were observed to invade the peripheral parts of the grafts. The capillary encroachment from the iris into the graft continued through the second day of transplantation. The host-graft anastomosis developed completely and became prominent and conspicuous after the third day of transplantation. Many capillaries were observed to encroach into the graft from the iris. The vasculature of the graft was increased in comparison with that of normal pancreatic tissue. This increase was prominent especially around pancreatic islet and ductal cells which survived after transplantation. Blood cells observed in these vessels of the graft indicated a functional state. The ultrastructure of the intrinsic blood vessels of the graft was intact and showed the peculiar fenestrations normally seen in the blood vessels of endocrine tissues. These observations indicated that pancreatic tissue fragments transplanted into the anterior eye chamber of rats were revascularized within 24 h. The revascularization was completed at the end of the third day of transplantation when definitive blood vessels linked the circulation of the graft with that of the iris.  相似文献   

5.
PURPOSE: Small intestinal transplantation remains a significant clinical problem. Allogeneic fetal intestinal (AFI) transplantation shows promise, particularly regarding procurement; however, no studiesto date have evaluated the potential success of true allogeneic loci implantation. The authors hypothesized that isolated segments of AFI could be heterotopically transplanted but would require immunosuppression to survive. METHODS: Donor tissue was obtained from late-gestation Brown Norway rat fetuses with a histo-locus RTN and Fischer fetuses with a histo-locus RT1L. The recipients were adolescent male Fischer rats with a histo-locus RT1L. A 1.2-cm segment of fetal small bowel was implanted in the omentum of the recipient rat and allowed to mature for 5 weeks. Animals were then separated into five groups. Group A served as controls with syngeneic fetal intestinal (SFI) transplant. Group B received AFI with no immunosuppression; group C, AFI transplant with five days of FK506; group D, AFI with 10 days of FK506; and Group E, AFI with daily FK506 for the entire 5-week maturation period. Animals were killed on day 35. RESULTS: All animals gained weight over the maturation period. Groups B, C, and D had no viable transplant segments at day 35. Groups A and E both had well-developed viable segments confirmed by gross and histological evaluation. CONCLUSIONS: FK506 allows for normal intestinal development for use in allogeneic fetal bowel transplantation. With this observation, the use of fetal intestine transplanted into the portal circulation emerges as a potentially viable alternative to present intestinal transplant models.  相似文献   

6.
The effect of bovine brain gangliosides was studied in rats lesioned by partial suction of the right somatosensory cortex and also in rats implanted with a piece of fetal brain tissue in this area. In both experiments a group of animals received 30 mg/kg i.p. of gangliosides daily for a period of 7 days after surgery. In lesioned rats, the untreated group showed a lower maintenance on a tight rope test at 7 as well as at 14 days, as compared with a sham-operated group (p < 0.05). In transplanted rats ganglioside treatment prevented the increase of the probability of falls from a horizontal bar at days 7 and 14 post-operations and the probability of slips on a vertical bar at day 7 (p < 0.05). Rats were killed at day 15 and brain coronal sections were obtained. Nuclear area and circularity were measured in a sample of cortical and grafted cells in a computer aid-image analyzer. Ganglioside protection on the normal size and shape of the nuclei in the ipsilateral cortex in lesioned as well as in transplanted rats (p < 0.01) was found. A higher nuclear area in ganglioside than in saline treated grafts was noted. Results suggest a protective action of the gangliosides against the lesion-induced motor dysfunction and secondary cortical cell degeneration.  相似文献   

7.
Fetal tissue transplantation has gathered considerable interest among researchers dealing with organ transplantation. A large number of studies concerning fetal intestinal transplantation have been published in the past 2 decades, almost all of them aiming to determine the feasibility of a properly functioning fetal transplant in continuity with the host's own enteral system. This study was designed to determine the absorptive capacity of the neogut in vivo, without anastomosing the transplant to the host's intestine, and to evaluate its use as an accessory enteral segment. Intestinal segments taken from Wistar albino fetuses were transplanted subcutaneously into the abdominal wall of 20 Sprague-Dawley rats. Immunosuppression was maintained by daily cyclosporin A (Cy A) 10 mg/kg injections s.c. and evaluated by determination of serum Cy A level and T-helper/T-suppressor cell ratio. The neogut was converted into a Thiry-Vella loop 2 weeks after transplantation. A test solution composed of 20% glucose and Trophamine was perfused via the stomas; glucose and amino acid absorption gradients were calculated. The gamma-glutamyl transferase (GGT) activity and mitotic index of the neogut were determined. Results were compared to those obtained from the host. There was no significant difference (P > 0.05) in glucose absorption between the neogut and the host tissue. Amino acid absorption and specific GGT activity were significantly less (P < 0.01) in the neogut. There was no significant difference (P > 0.05) between neogut and host intestine in mitotic index. Our data support the idea of using a transplanted fetal intestinal segment as an accessory feeding route.  相似文献   

8.
PURPOSE: To investigate the effect of fluorescein on human fetal neural retina and adult rat retina; and to use fluorescein to map the area of subretinal transplantation. METHODS: In vitro: Human fetal neural retina (8 to 14 weeks gestational age) was incubated in 0.03% fluorescein in Dulbecco's Modified Eagles Medium (DMEM) or DMEM alone for 30 min. Viability was determined using the trypan blue exclusion test, and results were compared. Effects of the fluorescein on cell morphology were assessed by observation of primary cultures for 1 week. In vivo: Human fetal neural retina was mechanically dissociated in 0.03% fluorescein in DMEM and transplanted to the subretinal space of immunosuppressed rats. To control for the effect of fluorescein on the grafted tissue, transplants were also performed in DMEM only. After transplantation, indirect ophthalmoscopy and true color fundus photography were performed to document the area covered by the transplant. One month after transplantation, the appearance of grafts exposed to fluorescein was compared to those that were not, at the light microscopic level. RESULTS: In vitro: Exposure of human fetal neural retina to fluorescein had no effect on viability. Similarly, in tissue culture, the fluorescein-exposed cells exhibited the same phenotype as the controls. In vivo: Immediately after transplantation the graft site was clearly outlined within the subretinal area and fluoresced intensely. There were no traces of the dye 2 h after transplantation. Cells that were transplanted with fluorescein survived transplantation, and one month after transplantation could be seen forming subretinal grafts. No differences were noted between these and control grafts. CONCLUSIONS: Fluorescein is an effective dye for immediate and transient localization of trans-scleral transplants to the subretinal space. It allows mapping of the area covered by the injection without interfering with the viability and differentiation of the transplanted cells. It allows unequivocal photo- and video-documentation in both the albino and pigmented fundi. It is already FDA approved for many other extra- and intraocular studies and now has directly been shown to be non-toxic to both human fetal neural retina and adult rodent retina.  相似文献   

9.
Cerebrovascular disease exemplifies the poor regenerative capacity of the CNS. While there are methods to prevent cerebral infarction, there is no effective therapy available to ameliorate the anatomical, neurochemical and behavioral deficits which follow cerebral ischemia. Focal and transient occlusion of the middle cerebral artery (MCA) in rodents has been reported to result in neuropathology similar to that seen in clinical cerebral ischemia. Using specific techniques, this MCA occlusion can result in a well-localized infarct of the striatum. This review article will provide data accumulated from animal studies using the MCA occlusion technique in rodents to examine whether neural transplantation can ameliorate behavioral and morphological deficits associated with cerebral infarction. Recent advances in neural transplantation as a treatment modality for neurodegenerative disorders such as Parkinson's disease, have revealed that fetal tissue transplantation may produce neurobehavioral recovery. Accordingly, fetal tissue transplantation may provide a potential therapy for cerebral infarction. Preliminary findings in rodents subjected to unilateral MCA occlusion, and subsequently transplanted with fetal striatal tissue into the infarcted striatum have produced encouraging results. Transplanted fetal tissue, assessed immunohistochemically, has been demonstrated to survive and integrate with the host tissue, and, more importantly, ameliorate the ischemia-related behavioral deficits, at least in the short term. Although, this review will focus primarily on cerebral ischemia, characterized by a localized CNS lesion within the striatum, it is envisioned that this baseline data may be extrapolated and applied to cerebral infarction in other brain areas.  相似文献   

10.
Sleep pressure and rebound comprise the two compensatory or “homeostatic” responses to sleep deprivation. Although sleep pressure is expressed by infant rats as early as postnatal day (P)5, sleep rebound does not appear to emerge until after P11. We reexamined the developmental expression of these sleep-regulatory processes in P2 and P8 rats by depriving them of sleep for 30 min using a cold, arousing stimulus delivered to a cold-sensitive region of the snout. This method effectively increased sleep pressure over the 30-min period (i.e., increases in the number of arousing stimuli presented over time). Moreover, sleep rebound (i.e., increased sleep during the recovery period) is demonstrated for the first time at these ages. Next, we showed that precollicular transections in P2 rats prevent sleep rebound without affecting sleep pressure, suggesting that the brainstem is sufficient to support sleep pressure, but sleep rebound depends on neural mechanisms that lie rostral to the transection. Finally, again in P2 rats, we used c-fos immunohistochemistry to examine neural activation throughout the neuraxis during sleep deprivation and recovery. Sleep deprivation and rebound were accompanied by significant increases in neural activation in both brainstem and hypothalamic nuclei, including the ventrolateral preoptic area and median preoptic nucleus. This early developmental expression of sleep pressure and rebound and the apparent involvement of brainstem and hypothalamic structures in their expression further solidify the notion that sleep–wake processes in newborns—defined at these ages without reference to state-dependent EEG activity—provide the foundation on which the more familiar processes of adults are built. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

11.
Using xeno-transplantation, interactions of neural tissues of vertebrates and insects were studied. Ventral neurogenic primordium of Notch Drosophila melanogaster embryos was transplanted into neural tube of amphibian and mammalian embryos with the aid of microhydrofeeding. Embryos of four different amphibian species, random bred mice and rats were used as graft recipients. It was concluded that there is a possibility to incorporate nerve cells of insects into the brain of vertebrates. Morphological and functional contacts can be established between the transplanted cells and host brain tissues. Transplanted Drosophila cells preserve their viability for a long time, so that a prolonged influence of the transplant upon the recipient can be predicted, which may be used in medical practice. A mixture of human fetal brain and Notch Drosophila melanogaster neural embryonic tissues were transplanted into the ventro-lateral nucleus of the thalamus of the patients of Parkinson' disease. As a result, tremor and constrained movements disappeared. Post-operation patients have been observed within 13-38 months. No side effects were noted during this time.  相似文献   

12.
The striatum of rats was lesioned by unilateral administration of MPP+. Two weeks later, a suspension of fetal mesencephalic cells (FMC), obtained from 14-day rat embryos, was injected into the lesioned striatum. Two weeks after grafting, the success of implantation and recovery of dopamine function were assessed by tyrosine hydroxylase immunocytochemistry (TH) and the measurement of striatal dopamine content. In addition, the extracellular concentrations of dopamine and dopamine metabolites were studied by microdialysis in vivo before and after perfusion of MPP+ to induce dopamine release from vesicular stores. TH+ cell bodies were seen in the lesioned grafted striata, indicating that fetal cells survived in these striata. In addition, there was a marked increase in TH-immunoreactivity in the neuronal fibers and terminals in the area surrounding the cell implant, suggesting a compensatory response of the host tissue which may involve fiber sprouting. Grafting induced a recovery in indices of dopamine function, including recovery in dopamine content, and basal and MPP+-induced dopamine release. Thus, grafts of FMC may provide a significant recovery of dopamine function in MPP+-lesioned striata.  相似文献   

13.
The transplantation of tissue containing dopamine-producing cells into the mammalian central nervous system is an emerging treatment for Parkinson's disease, despite relatively poor survival of implanted tissue. Recent evidence has suggested that Cytodex microcarriers enhance the survival of dopaminergic rat chromaffin cells transplanted into the rat striatum in the absence of immunosuppression. The current study was undertaken to evaluate the survival of rat and human fetal ventral mesencephalic neurons (VM) implanted alone or after attachment to microcarriers in the striatum of rats without immunosuppression. Rat fetal VM neurons demonstrated enhanced survival in the rat striatum when transplanted on microcarriers, compared to their transplantation alone during the 3-mo period examined in the present study. Transplants of human fetal VM neurons on microcarriers also survived remarkably well in the rat striatum without systemic immunosuppression. In contrast, human fetal VM cells transplanted alone into the rat striatum did not survive without systemic immunosuppression. There was no evidence of TH fiber sprouting in the vicinity of any transplant site. These data indicated that Cytodex microcarriers provide enhanced survival of both rat allograft and human xenograft fetal mesencephalic cells in the rat striatum without the necessity of systemic immunosuppression, perhaps by inducing a unique neuron-glia environment.  相似文献   

14.
Undifferentiated glandular stomach tissue fragments from 16.5-day fetal rats were transplanted under the kidney capsule of syngeneic adult rats, and the proliferation, differentiation and morphogenesis of the transplanted tissues were investigated. Gastric epithelial cells began to invaginate 3-4 days after the transplantation and immature glands were formed after 1 week. During the period, there was a gradual increase in the expression of pepsinogen and cathepsin E, markers of cytodifferentiation of the stomach epithelia, both at protein and mRNA levels. Cathepsin E was weakly expressed in undifferentiated gastric epithelial cells at 16.5 days of gestation, and a higher level of the expression was observed in differentiated epithelia of the transplants. In contrast, the pepsinogen-producing cells first appeared around days 3-4 after transplantation and gradually increased in number to about 30% of the epithelial cells and became localized at the bottom of the gland. During the period of the experiment up to 1 month, the pepsinogen-producing cells were all positive for class III mucin and cathepsin E, indicating the immature character of these cells. In addition, no parietal cells were observed. When the tissue fragments were transplanted into adrenalectomized animals, the epithelial differentiation and morphogenesis was suppressed, but its proliferation was enhanced. The observed changes were reversed by hydrocortisone replacement. These results suggest that the development of the 16.5-day fetal stomach is regulated intrinsically to a certain extent by the genetic program of the cells involved and various gastric functions develop in the absence of luminal stimulation, stage-specific systemic hormonal change, neuronal regulation or other systemic influences, and that glucocorticoids modulate the developmental program of the fetal stomach tissues.  相似文献   

15.
Young DA/HAN strain rats were submitted to an equilibrium test consisting in maintaining equilibrium upon a rotorod rotating at 10 or 20 rpm. They were either intact or lesioned, the lesion consisting in destruction of the inferior olivary complex (IOC) by 50-95 mg/kg i.p. administration of 3-acetylpyridine (3-AP) at day 15, followed, 2 to 4 h later, by i.p. injection of niacinamide (300 mg/kg). All the 3-AP-treated animals included in this study were completely lesioned, the extent of the lesion being estimated by both the response of the rats to harmaline and histological controls at the end of the experiments. The IOC lesioned rats were either naive (tested at one given day) or trained every day (10 trials per day); among the latters, some were trained before and after the lesion, the others being trained either before or only after. Control rats were submitted to the same training schedule. Both quantitative (time during which the animals maintained the equilibrium upon the rotating rod) and behavioral data (strategy used by the animals to maintain equilibrium) were obtained. The results demonstrate that, compared to those of controls rats, the quantitative and behavioral scores of the IOC lesioned animals were altered. Comparison of naive and trained animals shows that the impairment of the equilibrium behavior is not only due to the ataxia provoked by the IOC lesion but is also due to cognitive deficits. However, prelesion training facilitates the acquisition of a more efficient postlesion equilibrium behavior. From these results, it can be concluded that the olivo-cerebellar pathway is involved in the adaptation of motor behavior to the environmental conditions.  相似文献   

16.
Rats (n?=?11) with bilateral kainate lesions of the caudate nucleus and subsequent unilateral transplantation of embryonic striatal tissue into the damaged area preferred 4 months later to reach for food with the forepaw contralateral to the graft. No such asymmetry was observed in lesioned, nontransplanted (n?=?8) or unoperated (n?=?5) control rats. Good integration of the graft with the host brain was indicated by the finding that cortical spreading depression did not enter the lesioned caudate nucleus but did penetrate into the lesioned caudate with the graft almost as regularly as in intact rats. Behavioral asymmetry produced by unilateral grafts in bilaterally lesioned animals reveals the effects of transplantation with more sensitivity than the graft-induced compensation of the asymmetries caused by unilateral lesions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

17.
18.
We have studied the function of partial orthotopic liver transplantation in the rat by evaluating prothrombin time (PT), liver blood flow, basal and glucose-stimulated insulin secretion and glucose tolerance, and the reticuloendothelial function (RES) in hepatectomized rats subjected to partial liver transplantation. A graft corresponding to 68% of a normal liver was transplanted to totally hepatectomized rats. Comparison was made between control rats and rats subjected to 32% liver resection. PT was not significantly different in the transplanted group compared with liver-resected and control rats. Laser Doppler flowmetry showed that at 28 days after surgery, blood flow had increased in the transplanted livers. Furthermore, on the third day after transplantation, basal plasma insulin was increased and the plasma insulin response to glucose was exaggerated, suggesting reduced insulin action and impaired insulin degradation. Finally, uptake of radioactive-labeled E. coli bacteria, as a measure of RES function, was not compromised in transplanted animals. Based on these results, we conclude that reduced-size liver transplant in out-bred rats results in fast normalization of liver function after surgery although, immediately after surgery, glucose intolerance is seen.  相似文献   

19.
Differential growth of neural transplants as related to the age of the donor embryos was investigated in this study. Neocortical tissue of constant volume, obtained from embryos of 15, 16, 17, 18, 19, 20, and 21 days' gestational age, was transplanted into the cerebellum of 10-day-old rats. The fully grown transplants were analyzed quantitatively and qualitatively 90 days after transplantation. The ultimate volume of the transplants and the estimated total number of neurons in them followed a gradient in relation to the age of the donor embryos. At one extreme, the neural transplants from 15-day-old embryos grew very large, showing a 21-fold increase in size, and at the other extreme, those from 21-day-old embryos grew less than two-fold in volume. These differences were determined by the developmental history of the transplants. Neural tissue obtained from 15-day-old embryos contained predominantly neuroepithelial cells which continued to proliferate even after transplantation. This resulted in the large size of these transplants. At the other extreme, neural tissue from 21-day-old embryos contained predominantly preformed neuroblasts, and they simply differentiated afte transplantation. Due to this, the transplants were small in size. Neural tissues obtained from other embryos of different gestational ages between these two extremes contained neuroepithelial cells and preformed neuroblasts in differential ratios. The number of neuroepithelial cells in the transplants and their differential proliferative activity after transplantation, and the number of neuroblasts present, determined the differential sizes of these transplants. In histological preparations, all transplants were seen to contain normal-looking and well-differentiated neurons, and normal-looking neuropil. The transplants were integrated with the host brain, in that there was neither any gap nor any scar tissue between the transplants and the host neural tissue surrounding them. Neither the transplants nor the host brains showed any pathological reaction or neoplastic growth.  相似文献   

20.
The present study examined the effect of ibotenic acid lesions of the medial preoptic area (mPOA) on the expression of a conditioned place preference (CPP) for vaginocervical stimulation. Rats with bilateral lesions of the mPOA failed to display the CPP for vaginocervical stimulation shown by rats with sham or incomplete lesions. These findings provide additional support for the role of the mPOA in the neural circuitry underlying the reinforcing effects of female sexual behavior and raise the possibility that the altered pattern of approach and withdrawal behavior observed following lesions of the mPOA may be attributable in part to a diminution of the reinforcing effects of vaginocervical stimulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

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