Anatomy of the mastoid triangle and morphometric sex differences.

OBJECTIVE OF THE STUDY: This study aimed to quantify the area of the mastoid triangle (MT) and assess potential morphometric differences between males and females. PATIENTS: The sample consisted of 244 dry human skulls, with biological sex known based on genetic analysis, collected from a medicolegal osteological database from Central-Western Brazil. MATERIALS AND METHODS: The study was observational, analytical, and cross-sectional. The skulls were analyzed using Heron's equation to calculate the area of the MT. The landmarks connecting each of the sides of the triangle were: Porion (Po)>Mastoidale (Ma)>Asterion (Ast). Morphometric references were calculated and compared based on sex. RESULTS: The area of the MT was nearly 14% larger in males compared to females (p<0.05). The mean MT area for the right and left sides of males were 684.11±93.25mm2 and 668.94±111.95mm2, respectively. In females, the mean MT for the right and left sides were 588.93±91.09mm2 and 582.88±102.98mm2, respectively. Right and left side measurements were significantly different (p<0.05), except for Po-Ast (p=0.232). CONCLUSION: Morphometric features regarding the MT were slightly different between males and females. Application of the MT as a dimorphic tool should be adjuvant. Moreover, this tool should be considered carefully, especially because the sex-based differences were statistically significant, but discrete between males and females.

Influence of the Flowable Resin Layer on Bond Strength Between Resin Cement and a Universal Adhesive Applied in the Immediate Dentin-sealing Technique.

OBJECTIVES: The present study evaluated the influence of a flowable resin layer on bond strength between resin cement and a universal adhesive applied using an immediate dentin sealing (IDS) technique. METHODS AND MATERIALS: Coronary portions of bovine teeth were randomly divided into six groups (n=15). In the IDS.U group, the exposed dentin was immediately sealed with the Single Bond Universal adhesive (3M ESPE) following the self-etching protocol. In the IDS.UF group, a layer of Filtek Z350 (3M ESPE) flow resin was applied over the universal adhesive. In the DDS (control) group, the dentin was kept "fresh" and delayed dentin sealing was performed. After 24 hours in distilled water at 37°C, dentin surfaces were treated with pumice, phosphoric acid, and the application of the universal adhesive in the IDS.U and IDS. UF groups. The DDS group was treated with pumice and the universal adhesive was applied. The samples received cylinders of resin cement Rely X Ultimate (3M ESPE) made with the aid of starch tubes of 0.96 mm in diameter and 2 mm in length. They were submitted to the microshear bond strength test (µSBS) at 0.5 mm/min, after 24 hours (T1) and 3 months (T2). The fracture areas were evaluated qualitatively using a DSM 300 microscope (KOZO) with 45× magnification and classified as: adhesive, cohesive in cement, cohesive in dentin, or mixed. Samples were analyzed by scanning electron microscopy (SEM). The data were compared statistically between groups using the Kruskal-Wallis test, and intra-groups using the Mann-Whitney test (α=0.05). RESULTS: There were no significant differences between groups for the bond strength values (p>0.05). The IDS.UF group showed higher values at 3 months, when compared to the values of 24 hours (p<0.001). All groups showed a predominance of adhesive fracture (86.7% to 100%). SEM showed dentinal tubules exposed in the IDS.U and DDS groups; in the IDS.UF group, the tubules were completely sealed. CONCLUSIONS: The flow resin can be used on the adhesive when using the IDS technique because it increased the bond strength values after 3 months and promoted effective sealing of the dentinal tubules.

Functional integration of striatal allografts in a primate model of Huntington's disease.

Huntington's disease is an autosomal dominant, inherited disorder that results in progressive degeneration of the basal ganglia (especially the neostriatal caudate nucleus and putamen) and other forebrain structures and is associated with a clinical profile of movement, cognitive and psychiatric impairments for which there is at present no effective therapy. Neuropathological, neurochemical and behavioral features of the disease can all be reproduced in experimental animals by local injection of excitotoxic or metabolic toxins into the neostriatum. All these features of the disease can be alleviated, at least in rats, by transplantation of embryonic striatal tissue into the degenerated striatum, which was the basis for commencing the first clinical trials of striatal transplantation in Huntington's patients. However, although rat striatal xenografts may temporarily reduce apomorphine-induced dyskinesias in monkeys, there has been no demonstration that allograft techniques that work well in rats translate effectively to the much larger differentiated striatum of primates. Here we demonstrate good survival, differentiation and integration of striatal allografts in the primate neostriatum, and recovery in a test of skilled motor performance. Long-term graft survival in primates indicates probable success for clinical transplants in Huntington's disease; in addition, our data suggest that graft placement has a direct influence on the pattern and extent of functional recovery.

Reliability and validity of two software systems used to measure the pharyngeal airway space in three-dimensional analysis.

The aim of this study was to test the reliability and validity of two software systems used to measure the pharyngeal airway space three-dimensionally. A sample of 40 cone beam computed tomography images from adult patients was taken from a database. The cone beam computed tomography images were analysed by InVivoDental and Dolphin 3D software systems by two calibrated examiners. Three nasopharynx and oropharynx prototypes were used as a reference standard to validate the software systems. The volume, minimum area and minimum area localization were the measurements tested. Measurements were compared using a paired t-test; correlated using Pearson's correlation and linear regression. Bland-Altman analysis was also used. We found significant differences in the oropharynx volume (P=0.002) and nasopharynx minimum area localization (P=0.009). The Dolphin 3D software presented higher-volume values than the ones found in the prototype, while the InVivoDental software presented lower values. Strong (r>0.7; P>0.001) or very strong (r>0.9; P>0.001) correlations were observed between the software systems. Bland-Altman analysis found good agreement between prototypes and the software systems. The measurements obtained from the Dolphin 3D and InVivoDental software systems are both reliable, strongly correlated, but should not be assumed as equal. Dolphin 3D software overestimates the nasopharynx and oropharynx volumes, while the InVivoDental software underestimates them.

A simple breeding protocol for the procurement of accurately staged rat donor embryos for neural transplantation.

Obtaining accurately staged rat embryos can be difficult because of the variety of breeding protocols employed and because precise staging cannot be confirmed until excision of the embryos from the dam. The detection of estrus, pairing of animals, and confirmation of pregnancies is generally left to commercial suppliers, as in-house breeding can be laborious and unpredictable. Here we describe a simple, reliable in-house breeding protocol for the generation of accurately staged embryos as assessed by measurements of average crown to rump length (CRL).

Recovery of functional deficits following early donor age ventral mesencephalic grafts in a rat model of Parkinson's disease.

It has previously been reported that dopaminergic grafts derived from early donor age, embryonic age 12-day-old (E12) rat embryos produced a fivefold greater yield of dopamine neurons than those derived from conventional E14 donors. The present study addresses whether E12 grafts are able to ameliorate lesion-induced behavioral deficits to the same extent as E14 grafts. In a unilateral rat model of Parkinson's disease, animals received grafts derived from either E12 or E14 donor embryos, dispersed at four sites in the lesioned striatum. Both E12 and E14 grafts were able to induce recovery on both amphetamine and apomorphine rotation tests, and to ameliorate deficits in the cylinder, stepping test, and corridor tests, but were unable to restore function in the paw reaching task. E12 grafts were equivalent to E14 grafts in their effects on lesion-induced deficits. However, E12 grafts resulted in cell yields greater than previously reported for untreated primary tissue, with mean TH-positive cell counts in excess of 25,000 neurons, compared with E14 TH cell counts of 4000-5000 cells, representing survival rates of 75% and 12.5%, respectively, based on the expected adult complement. The equivalence of graft induced behavioral recovery between the two graft groups is attributed to a threshold number of cells, above which no further improvement is seen. Such high dopamine cell survival rates should mean that multiple, functioning grafts can be derived from a single embryonic donor, and if similar yields could be obtained from human tissues then the goal of one embryo per patient would be achieved.

A rat embryo staging scale for the generation of donor tissue for neural transplantation.

In rat models of Parkinson's and Huntington's diseases, embryonic neural cells obtained from embryos of specified ages can be implanted into the brain to partially restore both physiology and function. However, in litters produced using overnight mating protocols (often from commercial suppliers), the embryonic age can be difficult to determine precisely. As a result, embryonic size based on crown to rump length (CRL) is usually a more reliable method of embryo staging than the day of mating. This approach is not without difficulty. There are a number of rat staging scales in the literature, none of which deal with donor ages younger than E13, and there are discrepancies between scales at some donor ages. In the present article, we have devised a short mating-period protocol to produce precisely aged embryos. We show that CRL is a highly accurate, reproducible index of donor age and we present an updated embryonic staging scale for Sprague-Dawley (CD) rats that includes donor ages younger than those previously reported.

Improved survival of young donor age dopamine grafts in a rat model of Parkinson's disease.

In an attempt to improve the survival of implanted dopamine cells, we have readdressed the optimal embryonic donor age for dopamine grafts. In a rat model of Parkinson's disease, animals with unilateral 6-hydroxydopamine lesions of the median forebrain bundle received dopamine-rich ventral mesencephalic grafts derived from embryos of crown to rump length 4, 6, 9, or 10.5 mm (estimated embryonic age (E) 11, E12, E13 and E14 days post-coitus, respectively). Grafts derived from 4 mm embryos survived poorly, with less than 1% of the implanted dopamine cells surviving. Grafts derived from 9 mm and 10.5 mm embryos were similar to those seen in previous experiments with survival rates of 8% and 7% respectively. The best survival was seen in the group that received 6 mm grafts, which were significantly larger than all other graft groups. Mean dopamine cell survival in the 6 mm group (E12) was 36%, an extremely high survival rate for primary, untreated ventral mesencephalic grafts applied as a single placement, and more than fivefold larger than the survival rate observed in the 10.5 mm (E14) group. As E12 ventral mesencephalic tissues contain few, if any, differentiated dopamine cells we conclude that the large numbers of dopamine cells seen in the 6 mm grafts must have differentiated post-implantation. We consider the in vivo conditions which allow this differentiation to occur, and the implications for the future of clinical trials based on dopamine cell replacement therapy.

Amelioration of non-motor dysfunctions after transplantation of human dopamine neurons in a model of Parkinson's disease.

BACKGROUND: Patients suffering from Parkinson's disease (PD) display cognitive and neuropsychiatric dysfunctions, especially with disease progression. Although these impairments have been reported to impact more heavily upon a patient's quality of life than any motor dysfunctions, there are currently no interventions capable of adequately targeting these non-motor deficits. OBJECTIVES: Utilizing a rodent model of PD, we investigated whether cell replacement therapy, using intrastriatal transplants of human-derived ventral mesencephalic (hVM) grafts, could alleviate cognitive and neuropsychiatric, as well as motor, dysfunctions. METHODS: Rats with unilateral 6-hydroxydopamine lesions to the medial forebrain bundle were tested on a complex operant task that dissociates motivational, visuospatial and motor impairments sensitive to the loss of dopamine. A subset of lesioned rats received intrastriatal hVM grafts of ~9 weeks gestation. Post-graft, rats underwent repeated drug-induced rotation tests and were tested on two versions of the complex operant task, before post-mortem analysis of the hVM tissue grafts. RESULTS: Post-graft behavioural testing revealed that hVM grafts improved non-motor aspects of task performance, specifically visuospatial function and motivational processing, as well as alleviating motor dysfunctions. CONCLUSIONS: We report the first evidence of human VM cell grafts alleviating both non-motor and motor dysfunctions in an animal model of PD. This intervention, therefore, is the first to improve cognitive and neuropsychiatric symptoms long-term in a model of PD.

In vivo transgene expression from an adenoviral vector is altered following a 6-OHDA lesion of the dopamine system.

We have investigated the in vivo dynamics of an adenovirus-based, LacZ expressing vector, RAd36, at different doses, when injected unilaterally into the corpus striatum of normal rats. We have further investigated the characteristics of this vector in the presence of a 6-OHDA lesion of the nigrostriatal pathway. The dopamine-depleting lesion had an effect on both the number and the distribution of cells transduced by the adenoviral vector. The lesioned side of the brain contained significantly greater numbers of beta-galactosidase positive cells than the unlesioned side at 3 days, 1 week and 4 weeks post-injection and the distribution of transduced cells was altered by the presence of a dopamine lesion. We conclude that the increased levels of transgene expression seen in the lesioned hemisphere are due to a change in the diffusion characteristics of the injected vector in the lesioned hemisphere. These results indicate that, when investigating the use of virus-based vectors, ultimately for use in gene therapies in the CNS, the in vivo dynamics of the vector need to be assessed not only in the normal brain, but also in the pathological brain state such as animal models of target diseases.

Delivery of sonic hedgehog or glial derived neurotrophic factor to dopamine-rich grafts in a rat model of Parkinson's disease using adenoviral vectors Increased yield of dopamine cells is dependent on embryonic donor age.

The poor survival of dopamine grafts in Parkinson's disease is one of the main obstacles to the widespread application of this therapy. One hypothesis is that implanted neurons, once removed from the embryonic environment, lack the differentiation factors needed to develop the dopaminergic phenotype. In an effort to improve the numbers of dopamine neurons surviving in the grafts, we have investigated the potential of adenoviral vectors to deliver the differentiation factor sonic hedgehog or the glial cell line-derived neurotrophic factor GDNF to dopamine-rich grafts in a rat model of Parkinson's disease. Adenoviral vectors containing sonic hedgehog, GDNF, or the marker gene LacZ were injected into the dopamine depleted striatum of hemiparkinsonian rats. Two weeks later, ventral mesencephalic cell suspensions were prepared from embryos of donor ages E12, E13, E14 or E15 and implanted into the vector-transduced striatum. Pre-treatment with the sonic hedgehog vector produced a three-fold increase in the numbers of tyrosine hydroxylase-positive (presumed dopaminergic) cells in grafts derived from E12 donors, but had no effect on E13-E15 grafts. By contrast, pre-treatment with the GDNF vector increased yields of dopamine cells in grafts derived from E14 and E15 donors but had no effect on grafts from younger donors. The results indicate that provision of both trophic and differentiation factors can enhance the yields of dopamine neurons in ventral mesencephalic grafts, but that the two factors differ in the age and stage of embryonic development at which they have maximal effects.

Behavioral assessment of the ability of intracerebral embryonic neural tissue grafts to ameliorate the effects of brain damage in marmosets.

The transplantation of neuronal tissue into the brains of patients with Parkinson's disease is already being assessed as an experimental treatment for the symptoms of this disease, and the possibility of using similar graft tissue to ameliorate the symptoms of other neurodegenerative diseases is being considered. In this context, a small number of transplant experiments have been carried out in monkeys with lesions of the central dopamine and cholinergic systems. These experiments make it possible to determine the optimum methods of transplantation in an animal whose brain is structurally more closely related to the human than that of the rat and to assess the behavioral consequences of transplantation on symptoms that either resemble very closely the symptoms seen in patients, or are of a complex cognitive nature and are therefore more difficult to measure in the rat. It is intended that these experiments will contribute to the development of better treatments for the neurodegenerative diseases, either by the use of transplantation as a clinical treatment, or by contributing to a better understanding of the mechanisms that normally maintain neuronal function and that fail in these diseases.

The effects of donor stage on the survival and function of embryonic striatal grafts in the adult rat brain. I. Morphological characteristics.

The effects of the stage of donor embryos on the survival of grafts from different neuronal cell types have been well documented. Indeed, this parameter has been shown to be highly important in the survival and function of transplants of various tissues of the CNS. However this question has not been addressed in grafts of embryonic striatal tissue transplanted into animal models of Huntington's disease. In this study, rats which had received a unilateral ibotenic acid lesion in the dorsal striatum received grafts from a standard dissection of embryonic striatal primordium taken from donors of embryonic stage either E14, E16, E17 or E19 days. Three months after transplantation six rats from each group were killed for analysis of graft survival and morphology. The remaining animals in each group were killed between 10 and 14 months after grafting. Graft morphology was detected using a range of markers including: acetylcholinesterase and Cresyl Violet, the 32,000 mol. wt dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32), tyrosine hydroxylase and striatally-enriched phosphatase. All the grafts from different donor stages survived well at both time-points and Cresyl Violet staining indicated neuronal cell types spread throughout the grafts. The transplants were seen to have a characteristic "patchy" appearance with areas of dense AChE activity and DARPP-32 immunopositivity interspersed with areas of much lighter expression. These areas also co-localized consistently with striatally-enriched phosphatase and tyrosine hydroxylase expression, indicating that they comprised the striatal-like compartment of the graft (the so called P zones, containing cells of the mature striatum), and receiving specific afferent input from the host dopaminergic system. There was no significant difference in total graft volume, when comparing individual groups at both time-points from grafting. However, when comparing the volume of the P zones, the striatal primordium from the youngest donor stages (E14 and E16) produced grafts with a significantly higher proportion of striatal-like tissue. Therefore, in order to increase the proportion of striatal tissue within these grafts, tissue from younger embryonic donors should be used. This has important implications in the application of this model towards clinical trials in Huntington's disease.

Dopaminergic grafts implanted into the neonatal or adult striatum: comparative effects on rotation and paw reaching deficits induced by subsequent unilateral nigrostriatal lesions in adulthood.

We have examined whether dopaminergic mesencephalic grafts implanted into neonates can provide more extensive protection against deficits induced by a subsequent unilateral lesion of the mesotelencephalic dopaminergic pathway than when the grafts are implanted in adulthood. A dopamine-rich neuronal cell suspension obtained from embryonic day 14 mesencephali was injected unilaterally into the neostriatum of otherwise intact neonatal or adult rats at one day or two months of age, respectively. Two months later, the ipsilateral mesotelencephalic dopaminergic pathway was destroyed by unilateral injection of 6-hydroxydopamine. The behavioural effects of the grafts were evaluated in tests of drug-induced rotation and skilled paw reaching. After completion of the behavioural testing, animals were killed and brains were processed for tyrosine hydroxylase immunohistochemistry. In rats receiving transplants as adults, grafts were compact and located in the neostriatum. In contrast, in rats receiving transplants neonatally, fewer dopaminergic neurons survived and they were dispersed over a large area of the host neostriatum and nucleus accumbens. After lesioning, all animals manifested strong rotation in response to amphetamine: this was not initially prevented by the grafts, made at either age, up to three months following the lesion, but was reduced in both groups of grafted rats by seven months after lesioning. This prolonged period for the development of recovery contrasts markedly with the rapid recovery obtained when similar grafts are implanted into the denervated neostriatum of adult rats that had received a prior 6-hydroxydopamine lesion. The development of apomorphine rotation, thought to reflect the development of receptor supersensitivity following lesions, was partially blocked to a similar extent by the grafts in both age groups. In contrast to their effects in the rotation tests, the dopaminergic grafts had no detectable effect on the profound contralateral deficit induced by the lesions in the paw-reaching test, whether implanted into neonatal or adult brains. Thus, whereas the age of the host at the time of implantation can markedly influence the gross morphological organization of dopaminergic grafts implanted into the neostriatum, the functional effects were similar, whether the grafts were implanted into neonatal or adult hosts.

Cholecystokinin-dependent regulation of host dopamine inputs to striatal grafts.

Intrastriatal infusions of cholecystokinin-8-sulphate in the rat exerts a dose-dependent inhibition of dopamine-release from nigrostriatal terminals in the neostriatum, as measured by push-pull perfusion. This effect is abolished by excitotoxic lesions of the neostriatum, which, along with behavioural, electrophysiological and receptor binding studies, suggests that cholecystokinin exerts its action indirectly on dopamine release via receptors located on intrinsic striatal neurons. Grafts of embryonic striatum implanted in the lesioned striatum become innervated by host-derived dopamine axons and restore the response of those host neurons to cholecystokinin infusion. This suggests that the innervation of the grafts by dopaminergic axons of the host brain does not simply provide a tonic input to the grafts, but rather represents a phasic input that is under dynamic local regulation by graft-host feedback influences from the transplanted neurons themselves.

Dopamine-rich grafts in the neostriatum and/or nucleus accumbens: effects on drug-induced behaviours and skilled paw-reaching.

This study compares the behavioural efficiency of dopaminergic mesencephalic neurons implanted into the rat neostriatum and/or the nucleus accumbens. The dopaminergic mesotelencephalic pathway was unilaterally destroyed by injection of 6-hydroxydopamine into the medial forebrain bundle at the level of the lateral hypothalamus. Three weeks later, embryonic dopaminergic mesencephalic neurons were implanted into the denervated neostriatum, or the nucleus accumbens or into both locations (double grafts). All animals were tested over a four month period for amphetamine- and apomorphine-induced rotation, apomorphine-induced locomotor activity, and on a skilled paw reaching task. The characteristic ipsilateral rotation induced by amphetamine observed in lesioned animals was significantly reduced by neostriatal and double grafts, but persisted in animals with grafts in the nucleus accumbens alone. Four months after grafting, an overcompensation of rotation was observed for the neostriatal and double grafted animals, which now rotated contralaterally, i.e. away from the grafted side. The rotation induced by apomorphine in lesioned rats was decreased by neostriatal and double grafts and to a lesser extent by grafts implanted into the nucleus accumbens. Apomorphine-induced locomotor hyperactivity in lesioned animals was ameliorated by the nucleus accumbens and by double grafts. In the paw-reaching task, lesioned animals showed severe impairment in the use of the contralateral limb, which none of the grafts alleviated. Pretreatment with amphetamine had variable effects on the paw-reaching task which persisted in subsequent drug-free trials, suggesting that a conditioning mechanism may be involved. These findings suggest that the simultaneous reinnervation of the neostriatum and the nucleus accumbens by dopaminergic transplants is not sufficient to re-establish normal function in more complex behavioural tasks.

The effects of donor stage on the survival and function of embryonic striatal grafts in the adult rat brain. II. Correlation between positron emission tomography and reaching behaviour.

Grafts of embryonic striatal primordia are able to elicit behavioural recovery in rats which have received an excitotoxic lesion to the striatum, and it is believed that the P zones or striatal-like tissue within the transplants play a crucial role in these functional effects. We performed this study to compare the effects of different donor stage of embryonic tissue on both the morphology (see accompanying paper) and function of striatal transplants. Both the medial and lateral ganglionic eminence was dissected from rat embryos of either 10 mm, 15 mm, 19 mm, or 23 mm crown-rump length, and implanted as a cell suspension into adult rats which had received an ibotenic acid lesion 10 days prior to transplantation. After four months the animals were tested on the "staircase task" of skilled forelimb use. At 10-14 months rats from the groups which had received grafts from 10 mm or 15 mm donor embryos were taken for positron emission tomography scanning in a small diameter positron emission tomography scanner, using ligands to the dopamine D1 and D2 receptors, [11C]SCH 23390 and [11C]raclopride, respectively. A lesion-alone group was also scanned with the same ligands for comparison. Animals which had received transplants from the 10 mm donors showed a significant recovery with their contralateral paw on the "staircase test". No other groups showed recovery on this task. Similarly, the animals with grafts from the youngest donors showed a significant increase in D1 and D2 receptor binding when compared to the lesion-alone group. No increase in signal was observed with either ligand in the group which had received grafts from 15 mm donors. Success in paw reaching showed a strong correlation to both the positron emission tomography signal obtained and the P zone volume of the grafts. These results suggest that striatal grafts from younger donors (10 mm CRL) give greater behavioural recovery than grafts prepared from older embryos. This recovery is due to both the increased proportion of striatal-like tissue within the grafts and an increase in functional D1 and D2 dopamine receptors measured by positron emission tomography, i.e. a more extensive integration of the graft with the host brain.

Behavioural, histochemical and biochemical consequences of selective immunolesions in discrete regions of the basal forebrain cholinergic system.

The effectiveness of a recently developed immunotoxin, 192 IgG-saporin, was evaluated for making selective lesions of subgroups of basal forebrain cholinergic neurons. Following a pilot series of injections into the nucleus basalis magnocellularis to establish the effective dose for intraparenchymal lesions, separate groups of rats received injections of the immunotoxin into the septum, into the diagonal band of Broca or into the nucleus basalis magnocellularis. The lesions produced extensive and effective loss of cholinergic neurons in the discrete areas of the basal forebrain, as identified by loss of cells staining for acetylcholinesterase and p75NGFr, with a parallel loss of acetylcholinesterase staining and choline acetyltransferase activity in the target areas associated with each injection site in the dorsolateral neocortex, cingulate cortex and hippocampus. The selectivity of the lesion for cholinergic neurons was supported by the lack of gliosis and sparing of small to medium-sized cells at the site of injection of the toxin, including the glutamate decarboxylase immunoreactive cells that contribute to the septohippocampal projection. In spite of the extensive disturbance in the cholinergic innervation of the neocortex and hippocampus, immunotoxin lesions produced no detectable deficit in the Morris water maze task in any of the lesion sites within the basal forebrain. By contrast small but significant deficits were seen on tests of nocturnal activity (septal and nucleus basalis magnocellularis lesions), open field activity (septal and diagonal band lesions), passive avoidance (nucleus basalis magnocellularis lesions) and delayed non-matching to position (septal lesions). The results indicate that the 192 IgG-saporin provides a powerful tool for making effective lesions of the basal forebrain cholinergic neurons, and that the behavioural sequelae of such lesions warrant further detailed investigation.

Behavioral recovery after transplantation into a rat model of Huntington's disease: dependence on anatomical connectivity and extensive postoperative training.

Rats were trained to perform a conditioned stimulus-response task known to be sensitive to striatal damage, after which they received unilateral excitotoxic striatal lesions. The subsequent implantation of graft tissue into the lesioned striatum was either immediate (9 days) or substantially delayed (70 days). When retested 14 weeks later, all graft and lesion rats were equally impaired initially and biased their responding toward the ipsilateral side. Graft-associated recovery was evident with repeated postoperative testing, but only in rats that had received transplants 9 days postlesion. It is suggested that this training-dependent, graft-associated recovery is mediated specifically by the restored host-graft connections.

Septal grafts improve acquisition of an operant timing task after fimbria-fornix lesions in rats: Role of the interval between lesion and transplantation surgeries.

In a previous study we evaluated the conditions under which septal grafts could ameliorate performance of rats with fimbria-fornix lesions in an operant differential reinforcement of low rates of responding (DRL) task. Although the best recovery was demonstrated by the group in which the grafts were made 10 days following the lesion surgery, this factor (lesion-graft interval) was confounded with the developmental stage of the donor tissue, and it was suggested that the age of the embryonic donor was a more significant factor than the lesion graft interval in achieving good recovery. The present study provides a better control of embryonic age of the donor tissues, and we report that cholinergic rich septal grafts implanted into the host hippocampus either immediately or 11 days following fimbria-fornix lesion yielded better recovery than when the grafts were implanted after longer (8 weeks) lesion-graft intervals. In addition, grafts implanted into the intact hippocampus were without significant effect when the host rats were subjected to a delayed fimbria-fornix lesion made 10 weeks after graft implantation. These results corroborate the hypothesis of Nieto-Sampedro, Manthorpe and colleagues that 'wound-derived neurotrophic factors' can promote the functional viability of embryonic septal grafts in the hippocampus, even if such factors are not absolutely necessary for graft survival.