The standard posture is a myth: a scoping review.

BACKGROUND: The standard posture described in Kendall's manual is commonly used for postural assessment. However, no bibliographic reference was provided to support its use. OBJECTIVE: To identify the original source and the procedure followed for the design of that posture and to compare it with current literature on the subject. METHODS: In accordance with the PRISMA Extension for Scoping Reviews recommendations, PubMed and Scopus were searched using the terms "standing posture", "plum line," and "gravity line". Publications in English, French, German, or Spanish that referred to posture in adults without pathology were included. RESULTS: Six articles and 3 books were included in the final analysis. An identical posture to that described in Kendall's manual was identified in an early 19th-century work carried out with the unrealistic objective of maintaining static bipedal standing without muscular support, and including several anatomical misconceptions. Furthermore, the "ideal alignment" described in Kendall's manual does not correspond to the actual line of gravity, the comfortable posture, or natural postural compensations due to age, gender, or race. CONCLUSION: The utilization of this standard to ascertain postural deficiencies is not supported by current evidence and may result in numerous false positives, particularly in the elderly.

Study of paediatric patients with the clinical and biochemical phenotype of glucose transporter type 1 deficiency syndrome.

INTRODUCTION: Glucose transporter type 1 (GLUT1) deficiency syndrome may present a range of phenotypes, including epilepsy, intellectual disability, and movement disorders. The majority of patients present low CSF glucose levels and/or defects in the SLC2A1 gene; however, some patients do not present low CSF glucose or SLC2A1 mutations, and may have other mutations in other genes with compatible phenotypes. AIMS: We describe the clinical, biochemical, and genetic characteristics of the disease and perform a univariate analysis of a group of patients with clinical and biochemical phenotype of GLUT1 deficiency syndrome, with or without SLC2A1 mutations. MATERIAL AND METHODS: The study included 13 patients meeting clinical and biochemical criteria for GLUT1 deficiency syndrome. SLC2A1 sequencing and multiplex ligation-dependent probe amplification were performed; exome sequencing was performed for patients with negative results. RESULTS: Six patients presented the classic phenotype; 2 paroxysmal dyskinesia, 2 complex movement disorders, 2 early-onset absence seizures, and one presented drug-resistant childhood absence epilepsy. Six patients were positive for SLC2A1 mutations; in the other 5, another genetic defect was identified. No significant differences were observed between the 2 groups for age of onset, clinical presentation, microcephaly, intellectual disability, or response to ketogenic diet. Patients with SLC2A1 mutations presented more clinical changes in relation to diet (66.7%, vs 28.6% in the SLC2A1-negative group) and greater persistence of motor symptoms (66% vs 28.6%); these differences were not statistically significant. Significant differences were observed for CSF glucose level (34.5 vs 46mg/dL, P=.04) and CSF/serum glucose ratio (0.4 vs 0.48, P<.05). CONCLUSIONS: GLUT1 deficiency syndrome may be caused by mutations to genes other than SLC2A1 in patients with compatible phenotype, low CSF glucose level, and good response to the ketogenic diet.

Valorization of Sugarcane Straw for the Development of Sustainable Biopolymer-Based Composites.

Sugarcane straw (SCS) is a common agro-industrial waste that is usually incinerated or discarded in fields after harvesting, increasing the importance of developing added-value applications for this residue. In this study, sustainable biocomposites were produced, and the effect of sugarcane straw as a filler/reinforcement of commercial biopolymers was evaluated. Biocomposites were prepared using polylactic acid (PLA), polyhydroxybutyrate (PHB), polyhydroxybutyrate-co-hydroxyvalerate (PHBV), or green polyethylene (Green-PE) with different fiber contents (20, 30, and 40 wt.%). Dry-blending followed by compression molding was used for the biocomposites preparation. The results showed that PLA, PHB, and PHBV biocomposites retained the same impact strength as the neat matrices, even with 40 wt.% of sugarcane straw. The flexural and tensile modulus of PLA, PHB, and PHBV biocomposites increased with 20% of SCS, whereas, in Green-PE biocomposites, these properties increased at all fiber contents. Since any compatibilizer was used, both the flexural and tensile strength decreased with the addition of SCS. However, even with the highest content of SCS, the tensile and flexural strength values were around 20 MPa, making these materials competitive for specific industrial applications.

Exposure to 2.45 GHz radiofrequency modulates calcitonin-dependent activity and HSP-90 protein in parafollicular cells of rat thyroid gland.

In this study we analyzed the response of parafollicular cells in rat thyroid gland after exposure to radiofrequency at 2.45 GHz using a subthermal experimental diathermy model. Forty-two Sprague Dawley rats, divided into two groups of 21 rats each, were individually exposed at 0 (control), 3 or 12 W in a Gigahertz Transverse Electro-Magnetic (GTEM) chamber for 30 min. After radiation, we used simple or fluorescence immunohistochemistry to measure calcitonin cells or cellular stress levels, indicated by the presence hyperplasia of parafollicular cells, heat shock protein (HSP) 90. Immunomarking of calcitonin-positive cells was statistically significant higher in the thyroid tissue of rats exposed to 2.45 GHz radiofrequency and cell hyperplasia appeared 90 min after radiation at the SAR levels studied. At the same time, co-localized expression of HSP-90 and calcitonin in parafollicular cells was statistically significant attenuated 90 min after radiation and remained statistically significantly low 24 h after radiation, even though parafollicular cell levels normalized. These facts indicate that subthermal radiofrequency (RF) at 2.45 GHz constitutes a negative external stress stimulus that alters the activity and homeostasis of parafollicular cells in the rat thyroid gland. However, further research is needed to determine if there is toxic action in human C cells.

Hybrid Blood Collection Tubes: Combining the Best Attributes of Glass and Plastic for Safety and Shelf life.

SiO2 Medical Products, Inc. developed hybrid blood collection tubes (BCTs) that combine the breakage resistance of plastic and a shelf life approaching that of glass. These blended attributes provide improved BCT safety and reliability for patients and clinical workers. A shelf life of at least 2 y with less than 10% draw volume variation was demonstrated on evacuated hybrid BCTs, which is approximately 7 times longer than standard polyethylene terephthalate (PET) BCTs. This translates into more consistent and reliable blood draw volumes over a longer shelf life. The moisture vapor barrier of hybrid BCTs is 5 times lower than that of PET BCTs, which significantly reduces preservative evaporation over their shelf life. As a result, the risk of preservative gelation and alteration to the blood-to-preservative ratio mix is practically eliminated. Cyclic olefin polymer (COP) exhibits superior impact resistance to breakage because of its high ductility and impact strength and is not influenced by defects and flaws as is glass. Although COP has a mechanical toughness comparable with that of PET, it maintains this over a wider range of temperatures (-70 to 121 °C). As a result, COP can tolerate steam sterilization and cold storage temperatures without mechanical fatigue, deformation, or breakage. Lastly, extreme centrifugation of water-filled BCTs did not impose breakage of any kind.

Study of paediatric patients with the clinical and biochemical phenotype of glucose transporter type 1 deficiency syndrome. / Estudio de pacientes pediátricos con fenotipo clínico y bioquímico de síndrome de déficit de transportador de glucosa cerebral (GLUT-1).

INTRODUCTION: Glucose transporter type 1 (GLUT1) deficiency syndrome may present a range of phenotypes, including epilepsy, intellectual disability, and movement disorders. The majority of patients present low CSF glucose levels and/or defects in the SLC2A1 gene; however, some patients do not present low CSF glucose or SLC2A1 mutations, and may have other mutations in other genes with compatible phenotypes. AIMS: We describe the clinical, biochemical, and genetic characteristics of the disease and perform a univariate analysis of a group of patients with clinical and biochemical phenotype of GLUT1 deficiency syndrome, with or without SLC2A1 mutations. MATERIAL AND METHODS: The study included 13 patients meeting clinical and biochemical criteria for GLUT1 deficiency syndrome. SLC2A1 sequencing and multiplex ligation-dependent probe amplification were performed; exome sequencing was performed for patients with negative results. RESULTS: Six patients presented the classic phenotype; 2 paroxysmal dyskinesia, 2 complex movement disorders, 2 early-onset absence seizures, and one presented drug-resistant childhood absence epilepsy. Six patients were positive for SLC2A1 mutations; in the other 5, another genetic defect was identified. No significant differences were observed between the 2 groups for age of onset, clinical presentation, microcephaly, intellectual disability, or response to ketogenic diet. Patients with SLC2A1 mutations presented more clinical changes in relation to diet (66.7% vs. 28.6% in the SLC2A1-negative group) and greater persistence of motor symptoms (66% vs. 28.6%); these differences were not statistically significant. Significant differences were observed for CSF glucose level (34.5 vs. 46mg/dL, P=.04) and CSF/serum glucose ratio (0.4 vs. 0.48, P<.05). CONCLUSIONS: GLUT1 deficiency syndrome may be caused by mutations to genes other than SLC2A1 in patients with compatible phenotype, low CSF glucose level, and good response to the ketogenic diet.

EMF radiation at 2450 MHz triggers changes in the morphology and expression of heat shock proteins and glucocorticoid receptors in rat thymus.

AIMS: Electromagnetic fields (EMFs) can act as inducers or mediators of stress response through the production of heat shock proteins (HSPs) that modulate immune response and thymus functions. In this study, we analyzed cellular stress levels in rat thymus after exposure of the rats to a 2.45 GHz radio frequency (RF) using an experimental diathermic model in a Gigahertz Transverse Electromagnetic (GTEM) chamber. MAIN METHODS: In this experiment, we used H&E staining, the ELISA test and immunohistochemistry to examine Hsp70 and Hsp90 expression in the thymus and glucocorticoid receptors (GR) of 64 female Sprague­Dawley rats exposed individually to 2.45 GHz (at 0, 1.5, 3.0 or 12.0 W power). The 1 g averaged peak and mean SAR values in the thymus and whole body of each rat to ensure that sub-thermal levels of radiation were being reached. KEY FINDINGS: The thymus tissue presented several morphological changes, including increased distribution of blood vessels along with the appearance of red blood cells and hemorrhagic reticuloepithelial cells. Levels of Hsp90 decreased in the thymus when animals were exposed to the highest power level (12 W), but only one group did not show recovery after 24 h. Hsp70 presented no significant modifications in any of the groups. The glucocorticoid receptors presented greater immunomarking on the thymic cortex in exposed animals. SIGNIFICANCE: Our results indicate that non-ionizing sub-thermal radiation causes changes in the endothelial permeability and vascularization of the thymus, and is a tissue-modulating agent for Hsp90 and GR.

The effects of single and repeated exposure to 2.45 GHz radiofrequency fields on c-Fos protein expression in the paraventricular nucleus of rat hypothalamus.

This study investigated the effects of microwave radiation on the PVN of the hypothalamus, extracted from rat brains. Expression of c-Fos was used to study the pattern of cellular activation in rats exposed once or repeatedly (ten times in 2 weeks) to 2.45 GHz radiation in a GTEM cell. The power intensities used were 3 and 12 W and the Finite Difference Time Domain calculation was used to determine the specific absorption rate (SAR). High SAR triggered an increase of the c-Fos marker 90 min or 24 h after radiation, and low SAR resulted in c-Fos counts higher than in control rats after 24 h. Repeated irradiation at 3 W increased cellular activation of PVN by more than 100% compared to animals subjected to acute irradiation and to repeated non-radiated repeated session control animals. The results suggest that PVN is sensitive to 2.45 GHz microwave radiation at non-thermal SAR levels.

A study of neurotoxic biomarkers, c-fos and GFAP after acute exposure to GSM radiation at 900 MHz in the picrotoxin model of rat brains.

The acute effects of microwave exposure from the Global System for Mobile Communication (GSM) were studied in rats, using 900MHz radiation at an intensity similar to mobile phone emissions. Acute subconvulsive doses of picrotoxin were then administered to the rats and an experimental model of seizure-proneness was created from the data. Seventy-two adult male Sprague-Dawley rats underwent immunochemical testing of relevant anatomical areas to measure induction of the c-fos neuronal marker after 90min and 24h, and of the glial fibrillary acidic protein (GFAP) 72h after acute exposure to a 900MHz electromagnetic field (EMF). The experimental set-up facilitated measurement of absorbed power, from which the average specific absorption rate was calculated using the finite-difference time-domain (FDTD) 2h after exposure to EMF radiation at 1.45W/kg in picrotoxin-treated rats and 1.38W/kg in untreated rats. Ninety minutes after radiation high levels of c-fos expression were recorded in the neocortex and paleocortex along with low hippocampus activation in picrotoxin treated animals. Most brain areas, except the limbic cortical region, showed important increases in neuronal activation 24h after picrotoxin and radiation. Three days after picrotoxin treatment, radiation effects were still apparent in the neocortex, dentate gyrus and CA3, but a significant decrease in activity was noted in the piriform and entorhinal cortex. During this time, glial reactivity increased with every seizure in irradiated, picrotoxin-treated brain regions. Our results reveal that c-fos and glial markers were triggered by the combined stress of non-thermal irradiation and the toxic effect of picrotoxin on cerebral tissues.

The action of pulse-modulated GSM radiation increases regional changes in brain activity and c-Fos expression in cortical and subcortical areas in a rat model of picrotoxin-induced seizure proneness.

The action of the pulse-modulated GSM radiofrequency of mobile phones has been suggested as a physical phenomenon that might have biological effects on the mammalian central nervous system. In the present study, GSM-exposed picrotoxin-pretreated rats showed differences in clinical and EEG signs, and in c-Fos expression in the brain, with respect to picrotoxin-treated rats exposed to an equivalent dose of unmodulated radiation. Neither radiation treatment caused tissue heating, so thermal effects can be ruled out. The most marked effects of GSM radiation on c-Fos expression in picrotoxin-treated rats were observed in limbic structures, olfactory cortex areas and subcortical areas, the dentate gyrus, and the central lateral nucleus of the thalamic intralaminar nucleus group. Nonpicrotoxin-treated animals exposed to unmodulated radiation showed the highest levels of neuronal c-Fos expression in cortical areas. These results suggest a specific effect of the pulse modulation of GSM radiation on brain activity of a picrotoxin-induced seizure-proneness rat model and indicate that this mobile-phone-type radiation might induce regional changes in previous preexcitability conditions of neuronal activation.

AT514, a cyclic depsipeptide from Serratia marcescens, induces apoptosis of B-chronic lymphocytic leukemia cells: interference with the Akt/NF-kappaB survival pathway.

Clinical treatment of B-cell chronic lymphocytic leukemia (B-CLL) is limited by the progressive drug resistance and nonselectivity of most drugs towards malignant cells. Depsipeptides are present in certain bacteria and display potent antitumor activity. We have studied the effect of the novel cyclodepsipeptide AT514 (serratamolide) from Serratia marcescens on B-CLL cell viability. AT514 induced apoptosis of B-CLL cells from the 21 patients studied, as confirmed by Annexin-V binding and nuclei condensation, with an average IC50 of 13 microM. AT514 was effective in those B-CLL cases resistant to fludarabine, but had no effect on normal PBL. AT514 preferentially activated the intrinsic apoptotic pathway, as evidenced by loss of mitochondrial membrane potential, release of cytochrome c and activation of caspase-9 and -3, but not of caspase-8. Importantly, AT514 interfered with phosphatidylinositol-3 kinase and protein kinase C survival signals since it increased the apoptotic effect of LY294002 and Bisl inhibitors, and induced Akt dephosphorylation at Ser 473. AT514 also decreased NF-kappaB activity by dramatically reducing the levels of p65 in B-CLL. This was confirmed on functional assays using NF-kappaB-luc-transfected Raji cells and transgenic mice. Our results establish that AT514 induces apoptosis of primary B-CLL cells and could be useful for clinical treatment of this malignancy.

Adhesion to fibronectin via alpha4 integrin (CD49d) protects B cells from apoptosis induced by serum deprivation but not via IgM or Fas/Apo-1 receptors.

Apoptosis is a regulated event crucial to the development and proliferation of normal and malignant B cells. We have studied the role of signals delivered via alpha4 integrin on apoptosis triggered by three different pathways on these cells. For apoptosis induced by serum deprivation, culturing B cells on the recombinant fibronectin fragment H89, a known ligand for alpha4beta1 integrin, resulted in statistically significant (P < 0.005) higher viability values (68%, 65% and 67%) for Ramos, Nalm-6 and EHEB cells, respectively, than culturing cells on poly lysine (42%, 42% and 48%). An antialpha4 MoAb reverted the protecting effect, thus confirming that it was due specifically to alpha4 engagement. Similarly, cells cultured on FN-III4-5, a recently identified fibronectin region which binds activated alpha4 integrin, also showed statistically significant higher viability than poly lysine cultures. Alpha4 engagement however, did not prevent apoptosis induced on Ramos cells via surface IgM. Adhesion of IM-9 cells, a myeloma cell line carrying functional Fas receptors, to the H89 fragment neither increased cell viability upon triggering apoptosis via Fas when compared to poly lysine. These results indicate that alpha4 signalling may overcome B cell apoptosis induced by the lack of growth factors but does not seem to affect the IgM or Fas apoptotic pathways, thus suggesting different intracellular mechanisms for these processes.

Recovery after nigral grafting in 6-hydroxydopamine lesioned rats is due to graft function and not significantly influenced by the remaining ipsilateral or contralateral host dopaminergic system.

The aim of this study was to evaluate whether the recovery observed after grafting of fetal nigral cells in 6-hydroxydopamine lesioned rats is due to the graft itself, and whether the participation of the remaining host dopaminergic system is necessary. The effects of unilateral 6-hydroxydopamine lesion on rotational behavior were not significantly affected by sham grafting or by sham grafting plus repeat ipsilateral lesion, but were suppressed by nigral grafting, and by contralateral lesion. Immunohistochemical and in situ hybridization study of right striata of rats subjected to right-side lesion then right-side sham-grafting, and of right and left striata from rats subjected to right-side lesion then right-side sham-grafting then repeat right-side lesion then left-side lesion, revealed (a) no significant amphetamine-induced Fos activation, (b) marked increases in preproenkephalin mRNA levels, and (c) decreases in preprotachykinin levels, with no significant differences in any of these variables among these three types of striata. After nigral grafting, however, intense Fos expression was observed in the striatum, and preproenkephalin and preproenkephalin mRNA levels returned to normal. This recovery was maintained after subsequent repeat ipsilateral 6-hydroxydopamine lesion followed by contralateral lesion. The results demonstrate that, after dopaminergic denervation, the nigral graft itself is able to induce recovery in the assessed parameters, and that these effects of grafting into striata with maximal unilateral 6-hydroxydopamine lesion are due to graft function, and are not significantly influenced by the remaining ipsilateral or contralateral host dopaminergic system. Additionally, it is interesting to note that bilateral denervation led to changes in striatal preproenkephalin and preproenkephalin mRNA levels similar to those observed after unilateral lesion.

Striatal dopaminergic afferents concentrate in GDNF-positive patches during development and in developing intrastriatal striatal grafts.

Glial cell line-derived neurotrophic factor (GDNF) has potent trophic action on fetal dopaminergic neurons. We have used a double immunocytochemical approach with antibodies that recognize GDNF and tyroxine hydroxylase (TH) or the phosphoprotein DARPP-32, to study the developmental pattern of their interactions in the rat striatum and in intrastriatal striatal transplants. Postnatally, at one day and also at 1 week, GDNF showed a patchy distribution in the striatum, together with a high level of expression in the lateral striatal border, similar to that observed for the striatal marker DARPP-32 and also for TH. In the adult striatum, there was diffuse, weak immunopositivity for GDNF, together with widespread expression of DARPP-32-positive neurons and TH-immunoreactive (TH-ir) fibers. In 1-week-old intrastriatal striatal transplants, there were some GDNF immunopositive patches within the grafts and although there was not an abundance of TH-positive fibers, the ones that were seen were located in GDNF-positive areas. This was clearly evident in 2-week-old transplants, where TH-ir fibers appeared selectively concentrated in GDNF-positive patches. This pattern was repeated in 3-week-old grafts. In co-transplants of mesencephalic and striatal fetal tissue (in a proportion of 1:4), TH-ir somata were located mainly at the borders of areas that were more strongly immunostained for GDNF, and TH-ir fibers were also abundant in these areas and were found in smaller numbers in regions that were weakly positive for GDNF. These results demonstrate that GDNF-ir is coincident with that for TH and DARPP-32, and suggest that GDNF release by fetal striatal neurons both in normal development and in developing striatal grafts may have not only a trophic but also a tropic influence on TH-ir fibers and may be one of the factors that regulate dopaminergic innervation of the striatum.

The overall rod performance test in the MPTP-treated-mouse model of Parkinsonism.

We investigated the usefulness of the Overall Rotarod Performance (ORP) test for evaluating overall locomotory ability in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-injected-mouse model of Parkinson's disease (PD). For this procedure, the mice are pretrained on the rotarod and then tested at a series of increasing speeds, recording the time that the animal remains on the rod at each speed; the overall rod performance (ORP) of each animal is then calculated as the area under the curve in a plot of time-on-the-rod against rotation speed. At 15-day intervals, C57BL/6 mice were injected (or sham-injected) with MPTP, with ORP testing 7-10 days after each injection. After the fourth injection (day 45), mice in the treated group showed clearly lower ORP than mice in the control group (70-90% reduction in ORP), and were thus considered effectively lesioned. Subsequently, we investigated the short-term effects of apomorphine and L-DOPA on ORP in MPTP-treated mice. Apomorphine (at 0.5 or 2.5 mg/kg) had no significant effect, while L-DOPA (at 80 but not at 40 mg/kg) caused almost complete short-term recovery of pretreatment ORP. By about 100 days after the last MPTP injection, MPTP-treated mice showed partial long-term recovery of ORP; at this stage the mice were killed for tyrosine hydroxylase (TH) immunohistochemistry studies. TH immunoreactivity in the striatum showed a strong positive correlation with ORP as tested on day 100. We conclude that the ORP test is useful for evaluating motor deficit in MPTP-treated mice, and the effects of subsequent treatments.

The corticostriatal system mediates the "paradoxical" contraversive rotation but not the striatal hyperexpression of Fos induced by amphetamine early after 6-hydroxydopamine lesion of the nigrostriatal pathway.

In rats with unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway, amphetamine produces ipsiversive rotational behavior and activation of Fos in the intact striatum, but practically no activation of Fos in the denervated striatum. However, a seemingly paradoxical contraversive rotation, accompanied by intense striatal Fos activation in the lesioned striatum, has been observed during the first few days postlesion. In the present work, behavioral tests and immunohistochemistry for Fos protein and tyrosine hydroxylase (TH) were combined to study striatal changes 36 h after 6-OHDA lesion and particularly the possible involvement of glutamatergic corticostriatal afferents. Injection of amphetamine (0.5 mg/kg or 5 mg/kg) induced contraversive rotation and strong and evenly distributed Fos expression in the lesioned striatum; in the contralateral striatum, however, Fos density was lower than in nonlesioned rats. Pretreatment with the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK-801 (either 0.5 mg/kg or 5 mg/kg) did not significantly affect the hyperexpression of Fos in the lesioned striatum, but suppressed the contraversive rotation. Similarly, rats that were subjected to corticostriatal deafferentation (confirmed by sensory neglect tests) and 6-OHDA lesion (1 week or 3 weeks later) showed no significant reduction in the striatal Fos hyperexpression induced by amphetamine (0.5 mg/kg or 5 mg/kg) and no significant rotational asymmetry. In conclusion, the present results indicate that glutamatergic corticostriatal afferents are essential for the contraversive rotational behavior but not the striatal hyperexpression of Fos observed in response to amphetamine early after 6-OHDA lesion, and suggest that intense dopaminergic stimulation of striatal neurons is sufficient for induction of Fos, but that concurrent glutamatergic stimulation is necessary for the motor response.

Time course of striatal, pallidal and thalamic alpha 1, alpha 2 and beta 2/3 GABAA receptor subunit changes induced by unilateral 6-OHDA lesion of the nigrostriatal pathway.

Immunocytochemical techniques were used to investigate the distribution and abundance of GABAA receptor subunits (alpha 1, alpha 2 and beta 2/3) in the brains of unilaterally 6-OHDA-lesioned rats. Three and 7 days after lesion, the alpha 2-subunit was significantly more abundant in the lesion-ipsilateral striatum than in the lesion-contralateral striatum; by 4 weeks after lesion, however, no significant between-side differences were observed. Three and 7 days after lesion, the alpha 1-subunit was significantly less abundant in the lesion-ipsilateral globus pallidus than in the lesion-contralateral side; again, this difference disappeared within 4 weeks of lesion. Similarly, alpha 1 was initially less abundant in several relay thalamic nuclei on the lesioned side while alpha 2 was initially more abundant in intralaminar thalamic nuclei on the lesioned side. There were no significant between-side changes for the beta 2/3-subunits. Comparison of non-lesioned and 6-OHDA-lesioned rats revealed significant differences in brain areas which also showed differences on comparison of the lesioned and non-lesioned sides of 6-OHDA-lesioned rats. These results suggest that there is an early adaptation to the lesion, achieved through changes in GABAA receptor abundance. That some of these changes are no longer apparent after 4 weeks is due not only to partial reversion of the changes in the lesioned side but also to compensatory changes in the non-lesioned side.

Intrathalamic implants of GABA-releasing polymer matrices reduce motor impairments in rats with excitotoxically lesioned striata.

Current models of basal ganglia disorders suggest that the choreoathetosis is the end result of reduced GABAergic inhibition of the motor thalamus. GABA-releasing polymer matrices or control matrices without GABA were implanted either unilaterally or bilaterally in the vicinity of the ventromedial thalamic nucleus of normal rats and of rats with unilateral or bilateral excitotoxic striatal lesions (rat model of Huntington's disease), to study the effects of these GABA-releasing matrices on amphetamine-induced rotational behavior (unilateral implants in unilaterally lesioned rats) and on overnight spontaneous locomotor activity (bilateral implants in bilaterally lesioned rats). Unilateral implants led to a reduction (about 25%) in motor asymmetry; the response was transitory, probably because of the exhaustion of GABA release by the matrix. Some rats showed a more marked and permanent reduction of motor asymmetry, but this was probably due to lesion of the ventromedial nucleus or its thalamocortical projection. Bilateral implants of GABA-releasing matrices (but not control matrices) led to a marked (about 65%) but again transitory reduction in the locomotor hyperactivity induced by bilateral striatal lesion. These results suggest that implantation of a GABA-releasing source may be an effective alternative to intrathalamic fetal-tissue grafts or lesions as an experimental approach to the treatment of hyperkinetic movement disorders.

Time course of striatal changes induced by 6-hydroxydopamine lesion of the nigrostriatal pathway, as studied by combined evaluation of rotational behaviour and striatal Fos expression.

Changes taking place after unilateral 6-hydroxydopamine lesion of the dopaminergic nigrostriatal system have been studied by performing spontaneous, amphetamine-induced and apomorphine-induced rotational behaviour testing and tyrosine hydroxylase (TH) and Fos protein immunohistochemistry in the same rats. Apomorphine at a low dosage (0.25 mg/kg) induced contraversive rotation and supersensitive striatal Fos expression that were detected 24-48 h post-lesion and gradually increased in magnitude. Twenty-four hours after lesion, both high (5 mg/kg) and low doses (0.5 mg/kg) of D-amphetamine induced contraversive rotation and intense striatal Fos activation on the denervated side; however, only the higher dose induced Fos on the normal side. Two, 3 and 4 days after lesion, 0.5 mg/kg amphetamine induced contraversive rotation, but 5 mg/kg induced transitory contraversive rotation which switched to ipsiversive. In the normal striatum, only high doses of amphetamine induced Fos, but Fos induction in the denervated striatum was similar with both doses: areas showing severely decreased TH immunoreactivity still showed considerable Fos immunoreactivity, and some areas still showing TH immunoreactivity had higher Fos density than in the normal side. Seven and 14 days after lesion the loss of TH immunoreactivity and apomorphine-induced supersensitive Fos expression were more evenly distributed, and amphetamine induced only ipsiversive rotation and a low density of Fos-positive nuclei in the denervated striatum. These results indicate that the severe and progressive loss of dopaminergic terminals is counteracted by an early and rapidly progressing dopamine supersensitivity, together with a higher susceptibility to drug-induced dopamine release. This explains the apparently paradoxical contraversive rotation induced by amphetamine during the first week post lesion. However, experiments involving successive drug injections indicated that only the first amphetamine injection releases dopamine from the lesioned terminals.

Intrathalamic striatal grafts survive and affect circling behaviour in adult rats with excitotoxically lesioned striatum.

Current models of basal ganglia disorders suggest that choreoathetosis is the end result of reduced GABAergic inhibition of the motor thalamus. Graft-derived release of GABA from intrastriatal striatal grafts has also been reported. In the present work, cell suspension grafts from embryonic day 14-15 rat striatal primordia were implanted close to the ventromedial thalamic nucleus to investigate whether they can develop and survive in this ectopic location, and whether they induce changes in the circling behaviour of the host. The grafts were implanted either in normal rats or in rats whose striatum had been lesioned with ibotenic acid. These grafts were implanted either ipsilateral or contralateral to the lesioned striatum. Additionally, some rats received intrastriatal grafts, and lesioned but non-grafted rats and lesioned rats that had received injections of saline or of cell suspensions from fetal spinal cord in the thalamus were used as control. Four to eight months after transplantation, circling behaviour after amphetamine or apomorphine injection was evaluated. Serial sections were stained with Cresyl Violet and studied immunohistochemically with antibodies against DARPP-32 (dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein, as striatal marker), Fos protein, glutamate decarboxylase (67,000 mol. wt), glutamate decarboxylase (65,000 mol. wt) and GABA. Cresyl Violet sections showed that the intrathalamic striatal grafts developed into tissue masses resembling those observed in intrastriatal striatal grafts. DARPP-32 immunohistochemistry revealed that the grafts were composed of DARPP-32 immunoreactive (striatum-like) and DARPP-32-negative patches. The intrathalamic grafts of rats which had received a low dose of apomorphine (0.25 mg/kg) 2 h before perfusion showed clusters of intensely Fos-immunoreactive nuclei throughout the transplant, indicating that these cells had developed dopamine receptors and supersensitivity to dopamine agonists. Double Fos and DARPP-32 immunohistochemistry revealed that the Fos-positive nuclei were located in the striatum-like areas. Finally, the intrathalamic grafts also contained neurons immunoreactive to GABA and glutamate decarboxylase (65,000 and 67,000 mol. wt). Rats that had received intrathalamic grafts contralateral to the lesioned striatum (i.e. contralateral to the lesion-induced turning direction) showed a significant reduction of circling both after amphetamine (78% reduction) or apomorphine (77% reduction) injection. Rats that had received grafts ipsilateral to the lesioned striatum showed a 75% decrease in amphetamine-induced circling, but no significant change in apomorphine-induced circling. No significant drug-induced circling was observed in non-lesioned and grafted rats. Sham grafting (saline) or grafting of weakly GABAergic tissue (fetal spinal cord) had no significant effects on lesion-induced circling behaviour.(ABSTRACT TRUNCATED AT 400 WORDS)