Cortical Tissue Grafts Research Articles

Long-term function of ovarian tissue transplants

The long term duration of function of ovarian cortical tissue grafts is reviewed in this paper by describing cases of restoration of fertility by transplant of ovarian cortical tissue from matching donors where the recipient was in need of the transplant due to sterilizing effects of leukemia, premature ovarian failure (POF), and to reflect that it may be possible to postpone the normal time of menopause or to alleviate its symptoms.

Ovarian cryopreservation: experimental or established and a cure for the menopause?

Long-term (>7years) duration of function of ovarian cortical tissue grafts in three patients who have had several successful pregnancies is encouraging and requires us to carefully examine the risk benefit analysis of this technique for our future patients. However, the success rate for ovarian cryopreservation is unclear as the denominator (the number of women in whom frozen-thawed ovarian tissue has been re-implanted) is unknown. There still remain many unknowns and much more research is required before ovarian transplantation can be considered standard practice. The ability of ovarian cryopreservation to preserve fertility for some young survivors of cancer is proven, but the indications for which patients should be offered this exciting new technology are not yet established.

Neural transplants: effects on startle responses in neonatally MSG-treated rats

Neonatal monosodium glutamate (MSG) treatment has been associated with disfunctions in stress responses. Therefore, the present study aimed at examining the acoustic startle response (ASR) in MSG-treated rats and the effects of fetal neural transplantation. Male and female rats were given MSG (4 mg/g) or saline on alternate days from days 2–10 after birth. To determine whether fetal transplants could reverse behavioral impairments observed in MSG-treated rats, at 12 days of age MSG-treated rats received either arcuate nucleus (AN), cortical fetal grafts, or sham surgery into the third ventricle. ASR amplitude was measured at 35–40 days of age, and again in adulthood. MSG produced the expected decrease in the density of hypothalamic neuropeptide Y (NPY) and tyrosine hydroxylase (TH) in the AN area. Corticotropin-releasing factor (CRF) neurons/fibers were not affected by MSG. Pituitary atrophy was observed in all MSG rats. We report a permanent increase in the amplitude and reduction in short-term habituation of ASR in all MSG-treated rats. No effect was observed on long-term habituation in male rats. Cortical, but not AN tissue significantly reduced the magnitude of ASR in MSG animals. The results are discussed in terms of the central pathways mediating ASR, in particular hypothalamo-amygdala connections. It is considered that nonspecific factors mediate recovery produced by cortical tissue grafts, as observed in other models of neural transplan-tation.

Circadian locomotor rhythms in aged hamsters following suprachiasmatic transplant.

Circadian activity rhythms that have been eliminated by lesions of the suprachiasmatic nucleus (SCN) can be restored by fetal SCN grafts. Partial lesions of the host allow simultaneous expression of both donor and host rhythms. Because partial SCN ablation produces characteristic changes in activity rhythms that are similar to those that occur with age, including shortened period, reduced amplitude, and fragmentation, we investigated the extent to which fetal SCN grafts may be expressed by an animal whose activity rhythm exhibits these age-dependent changes. The results indicate that expression of a transplanted clock is possible in an unlesioned aged host. Grafts of fetal SCN into young hosts and cortical tissue grafts into intact aged hosts have no effect. In those aged animals that received SCN grafts, three patterns of expression emerged in the subsequent locomotor activity record: complete dominance of locomotor rhythmicity by the donor; relative coordination between donor and host rhythms; and spontaneous switching between host and donor phenotypes. The results suggest that the expression of rhythmicity by the grafted SCN may depend on the relative amplitude or strength of signals produced by the host and donor SCN.

Meninges play a neurotrophic role in the regeneration of vasopressin nerves after hypophysectomy

Following hypophysectomy the regenerating fibers of magnocellular neurons are known to establish new neurohemal connections with reorganized vasculatures in the median eminence, which lead to establishment of a posterior pituitary-like structure. In order to examine the role of the meninges (the pia mater and the arachnoid) in this regeneration process, we implanted the meningeal tissues obtained from neonatal rat pups into the third ventricle of the adult rats, and then hypophysectomized the host animals. Ten days after hypophysectomy, the meningeal tissue grafts were found to be densely innervated by regenerating vasopressin-immunoreactive fibers. Such fibers had dots and frequently formed large punctuations. On the contrary, few vasopressin fibers were found within the cortical tissue grafts. Further, the exposure of primary hypothalamic cell cultures to the medium conditioned by meningeal cell cultures promoted not only the survival of vasopressin-immunoreactive neurons but also the outgrowth and arborization of the neurites. The survivals of cortical and cerebellum neurons in culture were also promoted by the conditioned medium. These findings raise the possibility that the meninges play an important role in the axonal regeneration process after hypophysectomy.

Host resets phase of grafted SCN: influence of implant site, tissue specificity and pineal secretion

The suprachiasmatic nuclei (SCN) have daily fluctuations in energy consumption with glucose utilization high in the day, and low at night. In a previous study, we used [ 14C]2-deoxyglucose (2-DG) uptake to index the phase of the SCN, and found that in intact hamsters bearing SCN grafts in the third ventricle (3V), the native and grafted SCN, which were initially 12 h out of phase, became synchronized to the phase of the host clock [32]. In the present study, adult males (host animals) and pregnant females (source of donor tissue) were housed in opposite light-dark cycles. Host animals were sacrificed 14 days after implantation with either (1) SCN grafts into the lateral ventricle (LV), or (2) cortical grafts into 3V, or (3) SCN grafts in 3V of pinealectomized hamster. The results indicate that rhythms of 2-DG uptake are not induced in cortical tissue grafts, that the host SCN does not entrain SCN grafts located in the LV, and that entrainment of the grafted SCN (located in 3V) by the host circadian system occurs in the absence of pineal secretions.

An examination of prefrontal lesion size and the effects of cortical grafts on performance of the Morris water task by rats

We studied the effects of prefrontal cortex lesions and prefrontal cortical grafts on the performance of rats in the Morris water task. Adult male rats received cortical tissue grafts (E21) 2 weeks after aspiration of the medial prefrontal cortex. They were later studied in the Morris water maze, and their behavior was subsequently correlated with lesion size, graft presence, and graft size. The results showed that lesion size had a major effect on behavior: animals with lesions including the prelimbic cortex were unable to learn the location of the hidden platform, whereas those with lesions sparing this cortex eventually learned the task, although they were impaired relative to control animals. The presence of cortical grafts had no chronic effect upon behavior, and the size of the graft also did not predict behavior. True Blue injections into the host or graft in different animals showed that although the grafts invaded the hosts, the hosts did not invade the grafts themselves. These results are consistent with the growing body of evidence that suggests that cortical grafts do not allow the re-establishment of neural networks that replace the lost tissue, although there may be a general trophic effect of cortical grafts.

Frontal cortex grafts have opposite effects at different postoperative recovery times

We studied the effect of different postoperative times on the behavioral recovery following brain implants. Adult male rats received cortical tissue grafts 2 weeks after aspiration of the medial frontal cortex. Either 2 (Immediate Group) or 28 (Delay Group) days after grafting, the performance of these rats on a behavioral battery, comprising the Morris water maze task, forepaw use, and grooming, was compared to that of rats with similar lesions and postoperative recovery times but no grafts. Rats tested immediately after receiving implants performed better on the spatial navigation task than rats with similar lesions but no grafts. This improvement, however, was less than that shown by rats with lesions but no grafts permitted to recover for 28 days before testing. In contrast, in the Delay Group, rats with grafts were more greatly impaired than were their operated controls. Neither lesions nor grafts affected grooming although the Immediate Group with grafts were significantly more impaired in using their forepaws during feeding than were any of the other groups. These results lead us to conclude that differing postoperative recovery times and task requirements may account for some of the inconsistent results of the influence of brain grafts on behavioral recovery reported in the literature. We also conclude that cortical tissue implants can have two effects with different time courses and opposite net behavioral effects.

Partial recovery of gustatory function after neurol tissue transplantation to the lesioned gustatory neocortex

The ability of homotypic cortical tissue grafts to induce recovery of function after a gustatory neocortex (GN) lesion was studied using the conditioned taste aversion (CTA) paradigm. On acquisition day, 26 GN-lesioned and 8 sham-lesioned rats were presented with a saccharin solution, followed by an injection of the illness-inducing agent lithium chloride (LiCl). On the test day, 2 days later, saccharin was presented again. The GN-lesioned rats showed significantly less aversion to saccharin on the test day, indicating that the lesion impaired their ability to form taste-illness association. Nine of the lesioned rats were then bilaterally transplanted with fetal GN tissue. Nine weeks after the transplantation, the rats were presented with a LiCl solution, which served as both a tastant and an illness-inducing agent. An NaCl solution, which tasted very similar to the LiCl solution, was used to test the CTA to salt 3 days later. The nontransplanted rats consumed significantly more LiCl than the transplanted and sham-operated rats on the acquisition day, but both transplanted and nontransplanted rats consumed more NaCl than sham-operated rats on the test day. Nissl and Golgi stainings showed numerous somata and extensive arborization of neurons within the grafts. The results indicate that fetal GN grafts can restore the ability to integrate gustatory and visceral inputs but not to form long-lasting taste-illness associations.