Lesions Of Fimbria Research Articles

Identifying Diagnostic Markers for Early the Preneoplastic Transformation of Fimbria Lesions at the Origin of Ovarian Cancer in BRCA Mutated Patients

Identifying Diagnostic Markers for Early the Preneoplastic Transformation of Fimbria Lesions at the Origin of Ovarian Cancer in BRCA Mutated Patients

LAPAROSCOPIC DETECTION AND MANAGEMENT OF SUBTLE FIMBRIAL ABNORMALITIES AMONG INFERTILE WOMEN

Objective : To detect subtle fimbrial abnormalities by laparoscopy in infertile women and consequently to manage such cases.Material and Methods : Two hundred and eighty five patients with infertility underwent laparoscopy as a part of infertility evaluation at Mansoura University Hospital. During laparoscopy. fimbrial grasping by non-traumatic forceps and a probe were undertaken to evaluate the fimbrial end of the tube to detect any abnormalities. Serological testing for Chlamydia trachomatis was done in cases of fimbrial abnormalities and then following up pregnancy rate for at least one year.Results : Among 285 patients; 41(14.3%) patients had been found to have subtle fimbrial abnormalities in the form of fimbrial phimosis and agglutination. The technique was performed without significant complications. Chlamydia serology was observed in 26.8% of cases with subtle fimbrial abnormalities. The overall pregnancy rate was (36.5%). Conclusions : Laparoscopy still has its place for diagnosis and management of tubal factor infertility. Surgical correction of subtle fimbrial lesions may improve the fertility potential and increase pregnancy rate in infertile women.

Thalamic and hippocampal mechanisms in spatial navigation: A dissociation between brain mechanisms for learning how versus learning where to navigate

Various studies of hippocampus and medial thalamus (MT) suggest that these brain areas play a crucial, marginal, or no essential role in spatial navigation. These divergent views were examined in experiments using electrolytic Lesions of fimbria–fornix (FF) or radiofrequency or neurotoxic Lesions of MT of rats subsequently trained to find a stable visible (experiment 1) or hidden platform (experiments 2 and 3) in a water maze (WM) pool. Rats with electrolytic Lesions of FF or radiofrequency Lesions of MT were impaired in swimming to a stable visible platform, particularly the MT Lesion Group, suggesting impairment of WM strategies acquisition. Additional Lesioned rats were then tested in a hidden platform version of the WM task. Some rats were given Morris's nonspatial pretraining prior to Lesioning to provide them with training in the required WM behavioral strategies. Nonspatially Pretrained rats with FF Lesions eventually were able to navigate to the hidden platform, but the accuracy of place responding was impaired. This impairment occurred without problems in the motoric control of swimming or the use of WM behavioral strategies, suggesting that these rats had a spatial mapping impairment. Radiofrequency MT Lesions blocked acquisition of WM behavioral strategies by Naive rats throughout 3 days of training, severely impairing performance on all aspects of the hidden platform task. Nonspatially Pretrained rats given the same MT Lesions readily learned the hidden platform location and were indistinguishable from controls throughout spatial training. Rats given neurotoxic Lesions of MT for removal of cells were only mildly impaired and improved considerably during training, suggesting an important role for fibers of passage in WM strategies learning. The results provide a clear dissociation between a role for MT in learning WM behavioral strategies and the hippocampal formation in spatial mapping and memory. This is the first identification of a brain area, MT, that is essential for learning behavioral strategies that by themselves do not constitute the solution to the task but are necessary for the successful use of an innate learning ability: place response learning using spatial mapping.

Effects of Fimbria Lesions on Trace Two-Way Active Avoidance Acquisition and Retention in Rats

The fimbria-fornix (FF) is the main subcortical input to the hippocampus. It has been shown that FF lesions facilitate performance on a standard-delay two-way active avoidance task (AA2), thought to involve implicit memory. The hippocampal region is required for explicit or relational memory. It has been proposed that the hippocampus and related structures might associate events that are separated in space or time and detect elements shared in common by such discontiguous episodes. Therefore, FF lesions would be expected to impair performance on a trace paradigm, which introduces an interval between the CS (conditioned stimulus) and the US (unconditioned stimulus) and is generally considered a model of explicit memory. We predicted that FF lesions would impair memory in a trace AA2 procedure, while the same lesions would facilitate memory in a standard delay version of the task. To test this hypothesis, two experiments were carried out in 102 male Wistar rats. The first experiment characterized the trace paradigm using this kind of conditioning and demonstrated that control rats were able to acquire and retrieve (24 h and 11 days postacquisition) the association between the CS (tone) and the US (electric foot shock) when a trace interval (5, 10, or 20 s) was interposed between both stimuli. In the second experiment, we investigated the effects of FF electrolytic lesions on the same task using delay and trace (10-s trace interval) paradigms. Surprisingly, FF lesions facilitated the acquisition and the 24-h retention of the AA2 not only on the standart delay paradigm, but also with the trace paradigm. We suggest that facilitative effects could be a result of impairment in contextual learning.

Synthesis and behavioral evaluation of a chemical brain-targeting system for a thyrotropin-releasing hormone analogue

A chemical brain-targeting system, in which a redox 1,4-dihydropyridine < = > pyridinium function serves as a targeting moiety and a cholesteryl ester contributes to the improved penetration across the blood-brain barrier, was synthesized for a centrally active TRH analogue, pGlu-Leu-Pro-NH 2. Our retrometabolic design was also based on the progenitor sequence, Glu-Leu-Pro-Gly, where the C-terminal glycine (Gly) functions as an amide precursor via peptidyl glycine α-amidating monooxygenase (PAM) and glutamine (Gln) is the precursor of the N-terminal pyroglutamyl (pGlu) by glutaminyl cyclase. The molecular design included an endopeptidase (post-proline cleaving enzyme) cleavable spacer function. Treatment with the chemical targeting system significantly improved memory-related behavior, without altering thyroid function, in a passive avoidance paradigm in rats bearing bilateral fimbrial lesions.

Laparoscopic fimbrioplasty: an evaluation of 35 cases

The aim of this prospective study was to assess the value of laparoscopic treatment of severe fimbrial occlusions. During a period of 52 months infertile patients with fimbrial lesions were treated by operative laparoscopy. Only those patients requiring incision of the tubal serosa (salpingostomy) were included, representing the most severe lesions. The most frequent cases, those patients requiring simple adhesiolysis and deagglutination of the fringes, were excluded. All tubal lesions were documented carefully. Positive Chlamydia trachomatis (CT) serology was found in 65.7% of the patients. All the patients were followed up for at least 2 years. Three patients lost to follow-up were defined as failures. The global conception rate was 74.3%. The intrauterine pregnancy rate was 51.4%, and the 'take home baby rate' was 37.1% (only the first pregnancy being taken into account). The ectopic pregnancy rate was 22.9%. A positive CT serology was found to have a significant influence on the outcome. It can be concluded that the laparoscopic approach provides results similar to those obtained by microsurgery for the treatment of severe fimbrial occlusions, and represents an acceptable alternative to in-vitro fertilization (IVF) in selected cases.

Axotomized septal cholinergic neurons rescued by nerve growth factor or neurotrophin-4/5 fail to express the inducible transcription factor c-Jun

The inducible transcription factor c-Jun increases in neurons in response to axotomy by unknown mechanisms, and it has been postulated that c-Jun may regulate genes involved in promoting either degeneration or regeneration of axotomized neurons. In this report, we investigated the effect of daily or twice daily intraventricular administration of the neurotrophins nerve growth factor or neurotrophin-4/5 on the decrease in choline acetyltransferase expression and the increase in c-Jun expression in rat medial septum/diagonal band neurons three, seven and 14 days following unilateral, complete, fornix–fimbria lesion. We also examined whether medial septum/diagonal band neurons might die by apoptosis within two weeks of fornix–fimbria lesion using terminal deoxynucleotidyl transferase-mediated dUTP–biotin nick end labelling. Our results show that both nerve growth factor and neurotrophin-4/5 maintain the phenotype of basal forebrain cholinergic neurons following axotomy. Furthermore, using double-labelling immunofluorescence, we found that while c-Jun was expressed in cholinergic neurons in control-treated rats seven days following fornix–fimbria lesion, cholinergic neurons rescued by either nerve growth factor or neurotrophin-4/5 in neurotrophin-treated rats failed to express c-Jun. At no time-point (three, seven or 14 days post-axotomy) did any neurons in the medial septum/diagonal band stain positive for terminal deoxynucleotidyl transferase-mediated dUTP–biotin nick end labelling, suggesting that medial septum/diagonal band neurons do not undergo apoptosis within the first two weeks following axotomy at the time-points observed by us. Therefore, these results show that both nerve growth factor and neurotrophin-4/5 rescue the phenotype of axotomized cholinergic neurons and that these rescued neurons fail to express c-Jun in response to axotomy. In addition, since neither nerve growth factor nor neurotrophin-4/5 induced c-Jun in medial septum/diagonal band cholinergic neurons, it seems unlikely that the neurotrophic effects of nerve growth factor and neurotrophin-4/5 on cholinergic neurons are mediated via c-Jun expression. Furthermore, since axotomy failed to increase terminal deoxynucleotidyl transferase-mediated dUTP–biotin nick end labelling in septal neurons, it appears unlikely that c-Jun expression in these axotomized neurons is related to neuronal degeneration via apoptosis.

Hippocampal afferents to the rat prefrontal cortex: Synaptic targets and relation to dopamine terminals

Afferents to the prefrontal cortex (PFC) from the hippocampal formation and from midbrain dopamine (DA) neurons have been implicated in the cognitive and adaptive functions of this cortical region. In the present study, we investigated the ultrastructure and synaptic targets of hippocampal terminals, as well as their relation to DA terminals within the PFC of adult rats. Hippocampal afferents were labeled either by anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) from the ventral hippocampal formation or by anterograde degeneration following fimbria lesion. Hippocampal terminals in the PFC, identified by either method, formed primarily asymmetric axospinous synapses, with a small percentage forming asymmetric axodendritic synapses. Dopamine terminals in the PFC were identified by peroxidase immunocytochemistry for either tyrosine hydroxylase or DA and formed primarily symmetric synapses onto dendritic spines and small caliber dendritic shafts. Spines that received symmetric synaptic contact from DA terminals invariably also received an asymmetric synapse from an unlabeled terminal, forming a triadic complex. Hippocampal and DA terminals in the PFC were not often observed in the same area of the neuropil, and no examples of convergence of hippocampal and DA terminals onto common postsynaptic targets were observed. Further analysis revealed that spines receiving synaptic contact from hippocampal terminals did not receive additional synaptic contact from any other source. However, when localized to the same area of the neuropil, hippocampal and DA terminals were often in direct apposition to one another, without forming axo-axonic synapses. These results suggest that 1) hippocampal terminals primarily form excitatory synapses onto spiny pyramidal neurons, 2) hippocampal afferents are unlikely to be synaptically modulated by DA or non-DA terminals at the level of the dendritic spine, and 3) appositions between hippocampal and DA terminals may facilitate presynaptic interactions between these afferents to the PFC.

Long-term impoverished housing effects on morris maze performance after a fimbria lesion

Male Wistar rats received bilateral Fimbria lesions and were postoperatively housed in either standard social conditions or in impoverished conditions (one rat per cage) for 2 weeks in experiment I, and for 7 months in experiment II. The effects of lesion and housing conditions were investigated in the Morris maze spatial orientation task. Fimbria lesions increased the latency to reach the platform during acquisition in both experiments, which indicates that functional recovery of the Morris maze impairment does not occur in 7 months time. Post-operative impoverishment for 2 weeks or for 7 months reduced the lesion induced deficit in Morris maze acquisition, while it had a more general effect in the trial without platform. Interestingly, the impoverishment effects were not more severe after 7 months, but even less easily detected. These findings are interpreted as if impoverishment affects the reactiveness of animals to external stimuli, which may help the animal to compensate for the lesion-induced-deficit in Morris maze learning.

ACTH(4–9) analog ORG2766 treatment 7 months delayed still improves Morris maze performance of fimbria-lesioned rats

The ACTH(4–9) analog ORG2766 has been known to affect recovery of damaged functions resulting from injury to neural tissue. The peptides efficacy has often been ascribed to a facilitation of existing recovery, and immediate treatment seemed a prerequisite for efficacy. However, various results in other recovery paradigms do not refer to the neurotrophic properties of the peptide, but rather ascribe the effectiveness of ORG2766 to a general change in attention that indirectly affects functional recovery. Such a change in state is theoretically independent of the occurrence of spontaneous recovery, and, thus, treatment would not be required to coincide with recovery immediately after the damage. To see if ORG2766 can influence the recovery of function without the simultaneous occurrence of spontaneous recovery, this study employed a delay of 7 months after the occurrence of a fimbria lesion before ORG2766 was administered. The selective fimbria lesion produced an impairment in Morris maze performance, which could be attenuated by chronic treatment with ORG2766 immediately after the lesion as well as after 7 months. With respect to spatial orientation, no improvement is assessed in untreated lesioned rats, as the impairment of Morris maze performance in untreated fimbrialesioned rats is as severe as right after the lesion. The data indicates that efficacy of the ACTH(4–9) analog does not rely on the acceleration of spontaneous recovery processes in this paradigm. The behavioral effects of ORG2766 are discussed in the context of a peptide-induced state of enhanced attention.

Behavioral effects of basal forebrain grafts after dorsal septo-hippocampal pathway lesions

There are many reports that basal forebrain grafts ameliorate behavioral impairments produced by dorsal septo-hippocampal pathway lesions, but several studies have either found that this recovery may be unrelated to concomitant restitution of cholinergic markers, may be modest and depend on certain experimental conditions, or instead that grafts may actually exacerbate lesion-induced impairments. In this study, rats received one of three lesions of the dorsal septo-hippocampal pathways or a sham lesion, at 32 days of age, and intrahippocampal basal forebrain grafts or the vehicle control 10 days later. In grafted rats with total aspirative lesion of the fimbria-fornix, there was a substantial AChE-positive hippocampal reinnervation but no improvement of the severe lesion-induced spatial learning deficits, either reference memory or working memory, whether tested at 1 or 5 months post-grafting. In rats with bilateral medial fimbria lesions, grafts were successful, normal in appearance and produced substantial hippocampal cholinergic reinnervation; relative to non-grafted counterparts, however, grafted medial fimbria rats showed an early reference memory impairment and a persistent exacerbation of a working memory deficit. Exacerbation of learning impairments was also apparent in grafted rats with partial hippocampal denervation due to lesion of the cingulate and adjacent cortex above the fimbria-fornix. Nonetheless, basal forebrain grafts normalised general activity in these lesion groups, irrespective of whether the lesion-induced change was an increase or a decrease relative to controls. Graft-derived AChE-positive innervation was more marked than expected in both grafted cingulate-lesioned rats and grafted sham-lesioned rats, while control grafts of fetal cortex (above the septum) produced little or no AChE-positive innervation. Size of basal forebrain grafts, originally 3μ1 at two dorsal sites per hippocampus, increased markedly from rostral to caudal dorsal hippocampus in all groups but did not differ significantly across grafted groups, even with respect to non-lesioned rats. This study adds further evidence that basal forebrain grafts, successful with respect to cholinergic reinnervation, do not always enhance cognitive functions in rat hippocampal lesion models, and confirms that these grafts may have adverse effects after partial septo-hippocampal system lesions. It is important to attend to both the potential negative and positive effects of neural grafts.

Delayed matching-to-sample performance by rats in a new avoidance-motivated maze: Response to scopolamine and fimbria-fornix lesions

A new avoidance-motivated detour-maze in which memory for an immediately preceding sample event could be assessed was evaluated by testing seven 6-month-old male F-344 rats with a delayed matching-to-sample (DMTS) paradigm. Rats first received extensive pretraining with this paradigm over several months and after a minimum of 1,390 choice-trials demonstrated great proficiency in this maze. Studies were then conducted to establish cholinergic and hippocampal involvement in the DMTS task by using drug manipulations (scopolamine and physostigmine), and after lesions to the fimbria-fornix (FF) pathway. A high dose (1.0 mg/kg) of scopolamine but not a low dose (0.3 mg/kg) significantly interfered with choice accuracy as measured by errors and trials to criterion; physostigmine (0.01 and 0.03 mg/kg) had no significant effect; and fimbria lesions significantly disrupted both choice accuracy and runtime performance. Disruption was most pronounced on difficult problems (different paths to the goal). After lesions only, considerable within-trial perseverative errors occurred during the early postlesion weeks on four difficult problems from among the 18 tested. Results were discussed in terms of (a) specificity of this disruption, (b) indications of proactive interference effects, and (c) the movement-related excitation component of maze learning. The present results accord with earlier findings of disruption by scopolamine and FF lesions in a 14-unit T-maze, both mazes having similar performance requirements of shock avoidance and multiple 90-degree turns along the paths to the goal. The present results affirm that this new detour maze provides a viable approach for assessing cognitive performance in a within-subjects design and thereby offers new possibilities for testing various aspects of cognitive processing, particularly for aged rodent models, in a complex aversive situation.

Selective fimbria and thalamic lesions differentially impair forms of working memory in rats

Several series of experiments were designed to compare the effects of selective lesions of the fimbria or of thalamic nuclei on three different tasks involving working memory in rats: object recognition, place recognition, and the radial arm maze test. The main effects of fimbria lesions were as follows: they produced deficits in the radial maze; object recognition was spared or even facilitated, whereas place recognition was impaired. Electrolytic lesions of either centromedian-parafascicularis (CM-Pf) or dorsomedialis (DM) nuclei produced highly significant deficits in the radial maze test but spared object and place recognition. Ibotenate lesions of the CM-Pf had no effect on any test, which means that the critical structure in the effects of the electrolytic lesions of the CM-Pf was the fasciculus retroflexus (FR). These data may contribute two main points to animal models of hippocampal and thalamic amnesia: (1) different forms of working memory in rats might have different neural bases and (2) the FR may be involved in learning and memory processes.

Compensatory elevation of acetylcholine synthesis in vivo by cholinergic neurons surviving partial lesions of the septohippocampal pathway

The present study characterized the effects of partial destruction of the cholinergic septohippocampal pathway on transmitter functions of surviving cholinergic neurons in the hippocampus. Partial and full fimbrial transections were performed, and 3 weeks after lesioning, cholinergic functions were assessed in vivo and in vitro. Hippocampal ChAT activity and the capacity of hippocampal slices to synthesize [3H]ACh in vitro decreased by 35% and 45%, respectively, following partial fimbrial lesions and by 68% and 85%, respectively, following full fimbrial lesions. [3H]ACh release from hippocampal slices in vitro was decreased by 57% and 87%, respectively, following partial and full fimbrial lesions. Partial lesions decreased high-affinity choline uptake into hippocampal synaptosomes by 52%. In contrast to the significant reductions in cholinergic parameters measured in vitro after partial fimbrial lesions, such partial lesions did not significantly alter in vivo measures of hippocampal cholinergic function. Levels of endogenous ACh and choline measured in the hippocampus following partial lesions were similar to that of control values. Also, the hippocampal content of newly synthesized [2H4]ACh and the [2H4]ACh synthesis rate were not significantly different from control values. However, following full fimbrial lesions, in vivo measures of hippocampal cholinergic function were decreased to a degree similar to that observed in vitro. Hippocampal levels of endogenous ACh and [2H4]ACh and the synthesis rate for [2H4]ACh were decreased by 73%, 72%, and 83%, respectively. These results suggest that, following partial destruction of afferent cholinergic fibers that innervate the hippocampal formation, residual cholinergic neurons are able to upregulate their capacity to synthesize and store ACh in vivo, thus compensating for lesion-induced losses of cholinergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Confirmation of the Cholinergic Specificity of the Chol‐1 Gangliosides in Mammalian Brain Using Affinity‐Purified Antisera and Lesions Affecting the Cholinergic Input to the Hippocampus

An antiserum raised to Torpedo electromotor synaptosomal membranes (anti-TSM antiserum) induces a cholinergic-specific immune lysis of mammalian brain synaptosomes and recognizes a group of minor gangliosides appeared, therefore, to be specific to the cholinergic neuron and were designated Chol-1. To confirm the cholinergic specificity of the Chol-1 gangliosidic antigens, we have shown that not only does a mammalian ganglioside fraction that is enriched with respect to the Chol-1 gangliosides inhibit the cholinergic-specific immune lysis induced by the anti-TSM antiserum, but also it can be used to affinity-purify a subpopulation of immunoglobulins from the anti-TSM antiserum that also induce a cholinergic-specific lysis. Furthermore, we have demonstrated that fimbrial lesions, which cause a massive degeneration of cholinergic terminals in the ipsilateral hippocampus, lead to a loss of the Chol-1 gangliosides concomitant with that shown by choline acetyltransferase activity and that lesions to the entorhinal cortex, which cause a loss of mainly glutamergic synapses in the ipsilateral dentate gyrus leading to cholinergic sprouting from adjacent hippocampal areas and an increase in cholinergic markers in the dentate gyrus, produce concomitant increases in choline acetyltransferase activity and Chol-1 content. These results provide strong evidence in favour of the cholinergic specificity of the Chol-1 gangliosides.

Selective fimbria lesions impair acquisition of working and reference memory of rats in a complex spatial discrimination task

It has been reported that transections of the fimbria-fornix or lesions of the hippocampus selectively impair spatial working memory. Disruptive effects of these lesions on reference memory performance, however, have also been reported. We studied the effects of selective fimbria lesions on the acquisition of a complex spatial discrimination in the cone field. The cone field task is a place learning task that permits the simultaneous assessment of working and reference memory performance. Reproducible bilateral stereotaxic lesions were made by knife-cuts parallel to the midline. Sham lesions consisted of similar knife-cuts that were restricted to the overlying tissue. The rats were randomly started from 1 of 4 positions in order to prevent the development of a fixed food search pattern. On both memory components, fimbria-lesioned rats made about twice as many errors as the sham-lesioned and intact subjects, even after extensive training. Transection of the fimbria caused pronounced cholinergic denervation, predominantly at the more ventral part of the hippocampus, as indicated by reduced acetylcholinesterase histochemistry. Our results suggest a major role of the cholinergic innervation of the ventral hippocampus in spatial discrimination.

Effects of physostigmine and d-amphetamine on the behavior of rats with selective fimbria—fornix lesions and intrahippocampal fetal septal cell transplants

Female Long-Evans rats were given electrolytic lesions of either the medial fimbria bilaterally (Fi, n = 24), the dorsal fornix (Fo, n = 24), or both structures (FF, n = 24) at 31 days of age. Ten rats were given sham-operations. Ten days later, half the rats with lesions received bilateral intrahippocampal grafts of embryonic septal cell suspensions (FiT, FoT, FFT, respectively). As already reported in a separate publication (J.C. Dalrymple-Alford, C.R. Kelche, J.C. Cassel, G. Toniolo, V. Pallage, & B.E. Will, 1987, Experimental Brain Research, 210, 115-128), 7 months after transplant surgery, grafted rats were found to be more impaired in an eight-arm radial maze than nongrafted rats. The present report concerns a pharmacological study carried out in the same rats 11 months after grafting. We examined the effects of ip injections of physostigmine (0.01, 0.05, 0.10 mg/kg) and then of d-amphetamine (1.6 mg/kg), as compared with baseline control injections of saline. Just prior to the drug treatments, performances of grafted and nongrafted rats did not differ significantly, but impairments in grafted rats reappeared during subsequent no-injection and saline control trials. Physostigmine failed to affect significantly the performances in rats of any group. d-Amphetamine improved performances in grafted rats with medial fimbria lesions, impaired performances in grafted rats with dorsal fornix lesions, and did not change performances in grafted rats with both lesions, as compared with their respective nongrafted counterparts. Histological analysis revealed variable reinnervation of the host structure and substantial graft-induced lesions of the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of the damaged rat hippocampus with a locally applied electric field.

Previous studies have indicated that axons may be directed to regenerate toward the cathodal source of a locally applied D.C. electric field. In the present studies, similar galvanotropic effects were tested after partial denervation of the rat hippocampus. Following unilateral fimbrial lesions, 1.5 microA of direct current was applied locally to the tissue for 4 weeks. In the experimental group, the distal (temporal) portion of the hippocampus was located near the cathodal electrode, while the proximal (nasal) portion was located near the anode. In two control groups, either the current was reversed, or there was not current delivered to the tissue. Spontaneous alternation behavior 4 weeks post-operatively in the "cathode distal" rats provided results comparable to those in unoperated (normal) animals, whereas the control animals exhibited statistically significantly greater deficits in memory. The ability to learn the location of a submerged platform in a water tank was evident in unoperated and "cathode distal" animals, but not in either of the control groups. Hippocampal acetylcholinesterase activity in "cathode distal" animals was lower than in unoperated animals, but statistically significantly greater than in the other control animals. Results are consistent with the contention that locally applied weak direct current can modulate long term sequellae of hippocampal injury.

Behavioral deficits after intrahippocampal fetal septal grafts in rats with selective fimbria-fornix lesions.

Fetal septal transplants have been shown to promote behavioral recovery in young adult rats with aspiration fimbria-fornix lesions, rats with septal lesions and in intact aged rats. The present study examined the behavioral impact of intrahippocampal septal cell suspension transplants (T) in young female rats that had received, 10 days earlier, either medial fimbria lesions (Group FI.T), dorsal (subcallosal) fornix lesions (Group FO.T) or these two lesions together (Group FIFO.T). Relative to rats with lesions only (groups FI, FO and FIFO), grafted rats, irrespective of lesion locus, displayed unexpected impairments in (i) a serial alternation learning task, 5 weeks and 6 months after transplantation, and (ii) in a radial maze, 7 months after transplantation. In the first alternation test, Group FIFO showed impaired performance relative to Groups FI, FO and the sham-operated controls (Group S). In the second alternation test, Groups FO.T and FO showed impaired performance relative to Groups FI.T and FI, and only the performance of Group FI did not differ from that of Group S. In the radial maze, Groups FI, FO and FIFO all showed impaired performance relative to Group S. By contrast, there were no deleterious effects of lesions or of grafts in the acquisition and retention of a step-through passive avoidance task, 10 weeks after transplantation. Our findings on the effects of selective fimbria-fornix lesions did not confirm the report that rats with FI lesions but not those with FO lesions are unable to learn a serial alternation task, nor the report that FO lesions impair passive avoidance retention. Acetylcholinesterase (AChE) histochemistry revealed that grafts were present but graft-derived innervation of the host hippocampus varied from extensive to almost non-existent in all transplant groups. AChE-positivity in the dorsal hippocampus (DH) was not related to behavioral performance. However, the grafts often grew to a considerable size within the host brain and in many rats, especially those in Group FI.T, produced moderate to extreme damage of the host DH. There was a significant positive correlation between errors in the radial maze and graft-induced DH damage but no relationship between errors and graft size. The results indicate that, after partial lesions of the fimbria-fornix, intrahippocampal septal grafts survive well but are likely to damage recipient structures and result in behavioral impairments.

D-Amphetamine enhanced memory performance in rats with damage to the fimbria

Rats were preoperatively trained on a 5-unit linear maze and were then subjected to fimbria lesions. The animals were then retested on the same task with one group of rats with fimbria lesions and a control group being injected daily with 0.5 mg/kg d-amphetamine sulfate prior to testing. Lesions significantly impaired postoperative performance of the task, while amphetamine facilitated performance in fimbria lesioned rats. Due to an optimal learning of the task, performance of control animals was not significantly facilitated. These results raise several important issues including the mechanisms of functional recovery after brain lesions and the role of the hippocampal formation in learning and memory.