Evaluating Sex Steroid Hormone Neuroprotection in Spinal Cord Injury in Animal Models: Is It Promising in the Clinic?

The primary mechanism of traumatic spinal cord injury (SCI) comprises the initial mechanical trauma due to the transmission of energy to the spinal cord, subsequent deformity, and persistent compression. The secondary mechanism of injury, which involves structures that remained undamaged after the initial trauma, triggers alterations in microvascular perfusion, the liberation of free radicals and neurotransmitters, lipid peroxidation, alteration in ionic concentrations, and the consequent cell death by necrosis and apoptosis. Research in the treatment of SCI has sought to develop early therapeutic interventions that mitigate the effects of these pathophysiological mechanisms. Clinical and experimental evidence has demonstrated the therapeutic benefits of sex-steroid hormone administration after traumatic brain injury and SCI. The administration of estradiol, progesterone, and testosterone has been associated with neuroprotective effects, better neurological recovery, and decreased mortality after SCI. This review evaluated evidence supporting hormone-related neuroprotection over SCI and the possible underlying mechanisms in animal models. As neuroprotection has been associated with signaling pathways, the effects of these hormones are observed on astrocytes and microglia, modulating the inflammatory response, cerebral blood flow, and metabolism, mediating glutamate excitotoxicity, and their antioxidant effects. Based on the current evidence, it is essential to analyze the benefit of sex steroid hormone therapy in the clinical management of patients with SCI.

Development and Characterization of Electrodes Coated with Plasma-Synthesized Polypyrrole Doped with Iodine, Implanted in the Rat Brain Subthalamic Nucleus.

Biological treatments involve the application of metallic material coatings to enhance biocompatibility and properties. In invasive therapies, metallic electrodes are utilized, which are implanted in patients. One of these invasive therapeutic procedures is deep brain stimulation (DBS), an effective therapy for addressing the motor disorders observed in patients with Parkinson's disease (PD). This therapy involves the implantation of electrodes (IEs) into the subthalamic nucleus (STN). However, there is still a need for the optimization of these electrodes. Plasma-synthesized polypyrrole doped with iodine (PPPy/I) has been reported as a biocompatible and anti-inflammatory biomaterial that promotes nervous system regeneration. Given this information, the objective of the present study was to develop and characterize a PPPy/I-coated electrode for implantation into the STN. The characterization results indicate a uniform coating along the electrode, and physical-chemical characterization studies were conducted on the polymer. Subsequently, the IEs, both coated and uncoated with PPPy/I, were implanted into the STN of male rats of the Wistar strain to conduct an electrographic recording (EG-R) study. The results demonstrate that the IE coated with PPPy/I exhibited superior power and frequency signals over time compared to the uncoated IE (p < 0.05). Based on these findings, we conclude that an IE coated with PPPy/I has optimized functional performance, with enhanced integrity and superior signal quality compared to an uncoated IE. Therefore, we consider this a promising technological development that could significantly improve functional outcomes for patients undergoing invasive brain therapies.

Phytochemical Extract from Carica papaya Leaves and Punica granatum Seeds as Therapy Against Cognitive Impairment in a Murine Model.

Mild cognitive impairment (MCI) is defined as inter-stage between normal cognitive aging and major neurocognitive disorder (MND). This state of decay is a crucial factor in treatment to prevent the progression to MND. In this study, our group developed a virtual screening process to evaluate 2568 phytochemical compounds against 5 key proteins associated with MCI and MND. As a result, two potential candidates were identified: carpaine, found in Carica papaya leaves, and punicalagin, present in Punica granatum. A model of cognitive impairment (CI) was developed in 10-month-old male Sprague Dawley rats by administering aluminum chloride (AlCl3) at a dose of 100 mg/kg/day for 30 days. After AlCl3 administration period, one of the groups received carpaine and punicalagin in a phytochemical extract (PE) by oral gavage for 30 days. Novel object recognition test (NOR) was assessed at three different time points (T1 - before CI, T2 - after CI, and T3 - after PE treatment). Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were identified in the hippocampus of rats at the end of the study period. After administration of AlCl3, a reduction in discrimination index vs control rats (CI = 0.012 ± 0.08 vs Control = 0.076 ± 0.03), was observed. After phytochemical extract treatment, a significant increase in discrimination index values was observed in the PE group 0.4643 ± 0.13 vs CI group 0.012 ± 0.08. Additionally, the evaluation of immunohistochemistry showed an increase in GFAP positivity in the hippocampus of the CI groups, while a slight decrease was observed in the PE group. This work addressed a comprehensive methodology that utilized in silico tools to identify phytochemical compounds (carpaine and punicalagin) as potential candidates for affecting key proteins in CI. The phytochemical extract containing carpaine and punicalagin resulted in a trend in the decrease of GFAP expression in the hippocampus and improved recognition memory in rats with CI induced by age and AlCl3 administration.

Tibolone Improves Locomotor Function in a Rat Model of Spinal Cord Injury by Modulating Apoptosis and Autophagy.

Spinal cord injury (SCI) harms patients' health and social and economic well-being. Unfortunately, fully effective therapeutic strategies have yet to be developed to treat this disease, affecting millions worldwide. Apoptosis and autophagy are critical cell death signaling pathways after SCI that should be targeted for early therapeutic interventions to mitigate their adverse effects and promote functional recovery. Tibolone (TIB) is a selective tissue estrogen activity regulator (STEAR) with neuroprotective properties demonstrated in some experimental models. This study aimed to investigate the effect of TIB on apoptotic cell death and autophagy after SCI and verify whether TIB promotes motor function recovery. A moderate contusion SCI was produced at thoracic level 9 (T9) in male Sprague Dawley rats. Subsequently, animals received a daily dose of TIB orally and were sacrificed at 1, 3, 14 or 30 days post-injury. Tissue samples were collected for morphometric and immunofluorescence analysis to identify tissue damage and the percentage of neurons at the injury site. Autophagic (Beclin-1, LC3-I/LC3-II, p62) and apoptotic (Caspase 3) markers were also analyzed via Western blot. Finally, motor function was assessed using the BBB scale. TIB administration significantly increased the amount of preserved tissue (p < 0.05), improved the recovery of motor function (p < 0.001) and modulated the expression of autophagy markers in a time-dependent manner while consistently inhibiting apoptosis (p < 0.05). Therefore, TIB could be a therapeutic alternative for the recovery of motor function after SCI.

Gene expression and locomotor recovery in adult rats with spinal cord injury and plasma-synthesized polypyrrole/iodine application combined with a mixed rehabilitation scheme.

Introduction: Spinal cord injury (SCI) can cause paralysis, for which effective therapeutic strategies have not been developed yet. The only accepted strategy for patients is rehabilitation (RB), although this does not allow complete recovery of lost functions, which makes it necessary to combine it with strategies such as plasma-synthesized polypyrrole/iodine (PPy/I), a biopolymer with different physicochemical properties than PPy synthesized by conventional methods. After SCI in rats, PPy/I promotes functional recovery. Therefore, the purpose of this study was to increase the beneficial effects of both strategies and identify which genes activate PPy/I when applied alone or in combination with a mixed scheme of RB by swimming and enriched environment (SW/EE) in rats with SCI. Methods: Microarray analysis was performed to identify mechanisms of action underlying the effects of PPy/I and PPy/I+SW/EE on motor function recovery as evaluated by the BBB scale. Results: Results showed robust upregulation by PPy/I in genes related to the developmental process, biogenesis, synapse, and synaptic vesicle trafficking. In addition, PPy/I+SW/EE increased the expression of genes related to proliferation, biogenesis, cell development, morphogenesis, cell differentiation, neurogenesis, neuron development, and synapse formation processes. Immunofluorescence analysis showed the expression of ß-III tubulin in all groups, a decreased expression of caspase-3 in the PPy/I group and GFAP in the PPy/I+SW/EE group (p < 0.05). Better preservation of nerve tissue was observed in PPy/I and PPy/SW/EE groups (p < 0.05). In the BBB scale, the control group scored 1.72 ± 0.41, animals with PPy/I treatment scored 4.23 ± 0.33, and those with PPy/I+SW/EE scored 9.13 ± 0.43 1 month after follow-up. Conclusion: Thus, PPy/I+SW/EE could represent a therapeutic alternative for motor function recovery after SCI.

Inflammation: A Target for Treatment in Spinal Cord Injury.

Spinal cord injury (SCI) is a significant cause of disability, and treatment alternatives that generate beneficial outcomes and have no side effects are urgently needed. SCI may be treatable if intervention is initiated promptly. Therefore, several treatment proposals are currently being evaluated. Inflammation is part of a complex physiological response to injury or harmful stimuli induced by mechanical, chemical, or immunological agents. Neuroinflammation is one of the principal secondary changes following SCI and plays a crucial role in modulating the pathological progression of acute and chronic SCI. This review describes the main inflammatory events occurring after SCI and discusses recently proposed potential treatments and therapeutic agents that regulate inflammation after insult in animal models.

Rehabilitation on a treadmill induces plastic changes in the dendritic spines of spinal motoneurons associated with improved execution after a pharmacological injury to the motor cortex in rats.

Lesions to the corticospinal tract result in several neurological symptoms and several rehabilitation protocols have proven useful in attempts to direct underlying plastic phenomena. However, the effects that such protocols may exert on the dendritic spines of motoneurons to enhance accuracy during rehabilitation are unknown. Thirty three female Sprague-Dawley adult rats were injected stereotaxically at the primary motor cerebral cortex (Fr1) with saline (CTL), or kainic acid (INJ), or kainic acid and further rehabilitation on a treadmill 16 days after lesion (INJ+RB). Motor performance was evaluated with the the Basso, Beatie and Bresnahan (BBB) locomotion scale and in the Rotarod. Spine density was quantified in a primary dendrite of motoneurons in Lamina IX in the ventral horn of the thoracolumbar spinal cord as well as spine morphology. AMPA, BDNF, PSD-95 and synaptophysin expression was evaluated by Western blot. INJ+RB group showed higher scores in motor performance. Animals from the INJ+RB group showed more thin, mushroom, stubby and wide spines than the CTL group, while the content of AMPA, BDNF, PSD-95 and Synaptophysin was not different between the groups INJ+RB and CTL. AMPA and synaptophysin content was greater in INJ group than in CTL and INJ+RB groups. The increase in the proportion of each type of spine observed in INJ+RB group suggest spinogenesis and a greater capability to integrate the afferent information to motoneurons under relatively stable molecular conditions at the synaptic level.

Evolution of Spinal Cord Transection of Rhesus Monkey Implanted with Polymer Synthesized by Plasma Evaluated by Diffusion Tensor Imaging.

In spinal cord injury (SCI) there is damage to the nervous tissue, due to the initial damage and pathophysiological processes that are triggered subsequently. There is no effective therapeutic strategy for motor functional recovery derived from the injury. Several studies have demonstrated neurons growth in cell cultures on polymers synthesized by plasma derived from pyrrole, and the increased recovery of motor function in rats by implanting the polymer in acute states of the SCI in contusion and transection models. In the process of transferring these advances towards humans it is recommended to test in mayor species, such as nonhuman primates, prioritizing the use of non-invasive techniques to evaluate the injury progression with the applied treatments. This work shows the ability of diffusion tensor imaging (DTI) to evaluate the evolution of the SCI in nonhuman primates through the fraction of anisotropy (FA) analysis and the diffusion tensor tractography (DTT) calculus. The injury progression was analysed up to 3 months after the injury day by FA and DTT. The FA recovery and the DTT re-stabilization were observed in the experimental implanted subject with the polymer, in contrast with the non-implanted subject. The parameters derived from DTI are concordant with the histology and the motor functional behaviour.

Antihyperalgesic and Antiallodynic Effects of Amarisolide A and Salvia amarissima Ortega in Experimental Fibromyalgia-Type Pain.

Salvia amarissima Ortega is an endemic species of Mexico used in folk medicine to alleviate pain and as a nervous tranquilizer. The S. amarissima extract and one of its abundant metabolites, identified and isolated through chromatographic techniques, were investigated to obtain scientific evidence of its potential effects to relieve nociplastic pain such as fibromyalgia. Then, the extract and amarisolide A (3-300 mg/kg, i.p.) were pharmacologically evaluated in reserpine-induced fibromyalgia-type chronic pain and in depressive-like behavior (as a common comorbidity) by using the forced swimming test in rats. The 5-HT1A serotonin receptor (selective antagonist WAY100635, 1 mg/kg, i.p.) was explored after the prediction of a chemical interaction using in silico analysis to look for a possible mechanism of action of amarisolide A. Both the extract and amarisolide A produced significant and dose-dependent antihyperalgesic and antiallodynic effects in rats, as well as significant antidepressive behavior without sedative effects when the antinociceptive dosages were used. The 5-HT1A serotonin receptor participation was predicted by the in silico descriptors and was corroborated in the presence of WAY100635. In conclusion, S. amarissima possesses antihyperalgesic, antiallodynic, and anti-depressive activities, partially due to the presence of amarisolide A, which involves the 5-HT1A serotonin receptor. This pharmacological evidence suggests that S. amarissima and amarisolide A are both potential alternatives to relieve pain-like fibromyalgia.

An Exploration of Social Cognition in Children with Different Degrees of Genetic Deletion in Williams Syndrome.

An explanation for the social dysfunction observed in Williams syndrome may be deficits in social cognition. This study explored aspects of social cognition in children with Williams syndrome with different genotypes. The 12 participants included one with a 1.1 Mb deletion that retained the GTF2IRD1, GTF2I, and GTF2IRD2 genes, seven with a 1.5 Mb deletion that preserved the GTF2IRD2 gene, and four with a 1.8 Mb deletion with loss of all three genes. The participant retaining all three genes was found to have better performance on social judgment and first-order theory of mind tasks than the group with loss of all three genes. These results may reflect the influence of the GTF2I gene family on social cognition in Williams syndrome.

(-)-Epicatechin reduces muscle waste after complete spinal cord transection in a murine model: role of ubiquitin-proteasome system.

The skeletal muscle mass reduces 30-60% after spinal cord injury, this is mostly due to protein degradation through ubiquitin-proteasome system. In this work, we propose that the flavanol (-)-epicatechin, due its widespread biological effects on muscle health, can prevent muscle mass decrease after spinal cord injury. Thirty-six female Long Evans rats were randomized into 5 groups: (1) Spinal cord injury 7 days, (2) Spinal cord injury + (-)-epicatechin 7 days, (3) Spinal cord injury 30 days, (4) Spinal cord injury + (-)-epicatechin 30 days and (5) Sham (Only laminectomy). Hind limb perimeter, muscle cross section area, fiber cross section area and ubiquitin-proteasome system protein expression together with total protein ubiquitination were assessed. At 30 days Spinal cord injury group lost 49.52 ± 2.023% of muscle cross section area (-)-epicatechin treated group lost only 24.28 ± 15.45% being a significant difference. Ubiquitin-proteasome markers showed significant changes. FOXO1a increased in spinal cord injury group vs Sham (-)-epicatechin reduced this increase. In spinal cord injury group MAFbx increased significantly vs Sham but decrease in (-)-epicatechin treatment group at 30 days. At 7 and 30 days MuRF1 increased in the spinal cord injury and decreased in the (-)-epicatechin group. The global protein ubiquitination increases after spinal cord injury, epicatechin treatment induce a significant decrease in protein ubiquitination. These results suggest that (-)-epicatechin reduces the muscle waste after spinal cord injury through down regulation of the ubiquitin-proteasome system.

Recovery of motor function after traumatic spinal cord injury by using plasma-synthesized polypyrrole/iodine application in combination with a mixed rehabilitation scheme.

Traumatic spinal cord injury (TSCI) can cause paralysis and permanent disability. Rehabilitation (RB) is currently the only accepted treatment, although its beneficial effect is limited. The development of biomaterials has provided therapeutic possibilities for TSCI, where our research group previously showed that the plasma-synthesized polypyrrole/iodine (PPy/I), a biopolymer with different physicochemical characteristics than those of the PPy synthesized by conventional methods, promotes recovery of motor function after TSCI. The present study evaluated if the plasma-synthesized PPy/I applied in combination with RB could increase its beneficial effects and the mechanisms involved. Adult rats with TSCI were divided into no treatment (control); biopolymer (PPy/I); mixed RB by swimming and enriched environment (SW/EE); and combined treatment (PPy/I + SW/EE) groups. Eight weeks after TSCI, the general health of the animals that received any of the treatments was better than the control animals. Functional recovery evaluated by two scales was better and was achieved in less time with the PPy/I + SW/EE combination. All treatments significantly increased ßIII-tubulin (nerve plasticity) expression, but only PPy/I increased GAP-43 (nerve regeneration) and MBP (myelination) expression when were analyzed by immunohistochemistry. The expression of GFAP (glial scar) decreased in treated groups when determined by histochemistry, while morphometric analysis showed that tissue was better preserved when PPy/I and PPy/I + SW/EE were administered. The application of PPy/I + SW/EE, promotes the preservation of nervous tissue, and the expression of molecules related to plasticity as ßIII-tubulin, reduces the glial scar, improves general health and allows the recovery of motor function after TSCI. The implant of the biomaterial polypyrrole/iodine (PPy/I) synthesized by plasma (an unconventional synthesis method), in combination with a mixed rehabilitation scheme with swimming and enriched environment applied after a traumatic spinal cord injury, promotes expression of GAP-43 and ßIII-tubulin (molecules related to plasticity and nerve regeneration) and reduces the expression of GFAP (molecule related to the formation of the glial scar). Both effects together allow the formation of nerve fibers, the reconnection of the spinal cord in the area of injury and the recovery of lost motor function. The figure shows the colocalization (yellow) of ßIII-tubilin (red) and GAP-43 (green) in fibers crossing the epicenter of the injury (arrowheads) that reconnect the rostral and caudal ends of the injured spinal cord and allowed recovery of motor function.

Electroacupuncture and Curcumin Promote Oxidative Balance and Motor Function Recovery in Rats Following Traumatic Spinal Cord Injury.

Spinal cord injury (SCI) is a condition that puts the patient's life at risk in the acute phase and, during the chronic stage, results in permanent deficits in motor, sensory and autonomic functions. Isolated therapeutic strategies have not shown an effect on this condition. Therefore, this study aimed to evaluate the effects of electroacupuncture (EA) and curcumin, alone or combined, on the oxidative balance, motor function recovery and amount of preserved tissue following a traumatic SCI. Long-Evans rats were divided into five groups: SHAM, SCI, SCI + EA, SCI + Curcumin, and SCI + EA + Curcumin. Nitric oxide was significantly decreased in the Curcumin group; the EA, Curcumin and SCI + EA + Curcumin groups had significantly decreased hydroxyl radical and lipid peroxidation levels. Motor function recovery and the amount of preserved spinal cord tissue were significantly greater in the EA, Curcumin and EA + Curcumin groups. The results show that EA and Curcumin treatment alone or in combination decreased oxidative stress, improved functional motor recovery and increased the amount of preserved spinal cord tissue following a traumatic injury.

The Importance of Natural Antioxidants in the Treatment of Spinal Cord Injury in Animal Models: An Overview.

Patients with spinal cord injury (SCI) face devastating health, social, and financial consequences, as well as their families and caregivers. Reducing the levels of reactive oxygen species (ROS) and oxidative stress are essential strategies for SCI treatment. Some compounds from traditional medicine could be useful to decrease ROS generated after SCI. This review is aimed at highlighting the importance of some natural compounds with antioxidant capacity used in traditional medicine to treat traumatic SCI. An electronic search of published articles describing animal models of SCI treated with natural compounds from traditional medicine was conducted using the following terms: Spinal Cord Injuries (MeSH terms) AND Models, Animal (MeSH terms) AND [Reactive Oxygen Species (MeSH terms) AND/OR Oxidative Stress (MeSH term)] AND Medicine, Traditional (MeSH terms). Articles reported from 2010 to 2018 were included. The results were further screened by title and abstract for studies performed in rats, mice, and nonhuman primates. The effects of these natural compounds are discussed, including their antioxidant, anti-inflammatory, and antiapoptotic properties. Moreover, the antioxidant properties of natural compounds were emphasized since oxidative stress has a fundamental role in the generation and progression of several pathologies of the nervous system. The use of these compounds diminishes toxic effects due to their high antioxidant capacity. These compounds have been tested in animal models with promising results; however, no clinical studies have been conducted in humans. Further research of these natural compounds is crucial to a better understanding of their effects in patients with SCI.

Cognitive, Behavioral, and Adaptive Profiles in Williams Syndrome With and Without Loss of GTF2IRD2.

Williams syndrome (WS) is a neurodevelopmental disorder that results from a heterozygous microdeletion on chromosome 7q11.23. Most of the time, the affected region contains ~1.5 Mb of sequence encoding approximately 24 genes. Some 5-8% of patients with WS have a deletion exceeding 1.8 Mb, thereby affecting two additional genes, including GTF2IRD2. Currently, there is no consensus regarding the implications of GTF2IRD2 loss for the neuropsychological phenotype of WS patients. OBJECTIVES: The present study aimed to identify the role of GTF2IRD2 in the cognitive, behavioral, and adaptive profile of WS patients. METHODS: Twelve patients diagnosed with WS participated, four with GTF2IRD2 deletion (atypical WS group), and eight without this deletion (typical WS group). The age range of both groups was 7-18 years old. Each patient's 7q11.23 deletion scope was determined by chromosomal microarray analysis. Cognitive, behavioral, and adaptive abilities were assessed with a battery of neuropsychological tests. RESULTS: Compared with the typical WS group, the atypical WS patients with GTF2IRD2 deletion had more impaired visuospatial abilities and more significant behavioral problems, mainly related to the construct of social cognition. CONCLUSIONS: These findings provide new evidence regarding the influence of the GTF2IRD2 gene on the severity of behavioral symptoms of WS related to social cognition and certain visuospatial abilities. (JINS, 2018, 24, 896-904).

Effect of the combined treatment of albumin with plasma synthesised pyrrole polymers on motor recovery after traumatic spinal cord injury in rats.

Traumatic spinal cord injury (TSCI) is a health problem for which there is currently no treatment or definitive therapy. Medicine has explored therapeutic options for patients with TSCI with the aim to improve their quality of life. One alternative has been the development of biomaterials that offer neuroprotection or neuroregeneration of damaged nerve tissue. The microinjection of iodine-doped polypyrrole particles synthesised by plasma (PPPy/I) has shown neuroprotective effects that favour motor function recovery in experimental animals with TSCI. However, their ability to migrate into the tissue has led to the need to test a suspension vehicle that enables the concentration of particles at the site of injury. To achieve this, two biomaterials of PPPy/I (P1 and P2) were studied. The superficial physicochemical characterisation of the polymers was performed by infrared spectroscopy, X-ray photoelectron spectroscopy and contact angle. The rheological performance under oscillatory shear rate of suspensions containing both polymers alone and in combination with bovine serum albumin was also studied. In vivo tests were performed on animals with and without TSCI that were microinjected with particles of P1 or P2 in suspension using a solution of rat serum albumin. Exposure to the protein solutions generates a protein multilayer on the surface of the biomaterials that can drastically change the behaviour of both P1 and P2, which led to severe repercussions in the in vivo assays. The results showed that surface chemistry plays an important role in the performance and that it is possible to treat TSCI with these materials. The interaction of the surface of materials PPPy/I.1 (P1) and PPPy/I.2 (P2) with bovine serum albumin (BSA) resulted in a series of changes in the surface chemistry of both biomaterials. The contact angle study (Fig. A) showed the presence of a critical BSA concentration ([BSA]c), in which a monolayer was formed on both polymers and then a stable protein multilayer, as evidenced by the establishment of a plateau in the determination of the contact angle. In vivo tests showed that this interaction may be beneficial in the treatment of traumatic spinal cord injury (TSCI), depending on the surface characteristics with or without rat serum albumin (RSA). The TSCI + P1 and TSCI + P2 + RSA groups obtained significant differences in functional recovery compared with the control group according to the Basso, Beattie and Bresnahan scale (BBB).

Delayed injection of polypyrrole doped with iodine particle suspension after spinal cord injury in rats improves functional recovery and decreased tissue damage evaluated by 3.0 Tesla in vivo magnetic resonance imaging.

BACKGROUND CONTEXT: Traumatic spinal cord injury (SCI) causes irreversible damage with loss of motor, sensory, and autonomic functions. Currently, there is not an effective treatment to restore the lost neurologic functions. PURPOSE: Injection of polypyrrole-iodine(PPy-I) particle suspension is proposed as a therapeutic strategy. STUDY DESIGN: This is an in vivo animal study. METHODS: This study evaluates the use of such particles in rats after SCI by examining spared nervous tissue and the Basso, Beattie, and Bresnahan (BBB) scale to evaluate the functional outcome. Diffusive magnetic resonance imaging (MRI) was employed to measure the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) as non-invasive biomarkers of damage after SCI. RESULTS: Fractional anisotropy decreased, whereas ADC increased in all groups after the lesion. There were significant differences in FA when compared with the SCI-PPy-I group versus the SCI group (p<.05). Significant positive correlations between BBB and FA (r2=0.449, p<.05) and between FA and preserved tissue (r2=0.395, p<.05) were observed, whereas significant negative associations between BBB and ADC (r2=0.367, p<.05) and between ADC and preserved tissue (r2=0.421, p<.05) were observed. CONCLUSIONS: The results suggested that PPy-I is neuroprotective as it decreased the amount of damaged tissue while improving the motor function. Non-invasive MRI proved to be useful in the characterization of SCI and recovery.

Nanotechnology as Potential Strategy for the Treatment of Pharmacoresistant Epilepsy and Comorbid Psychiatric Disorders.

BACKGROUND: Pharmacoresistant epilepsy is a disabling neuronal disorder with harmful consequences that impact patient's quality of life. Although psychiatric comorbidities are frequently present in patients with epilepsy, they are more common in those patients with pharmacoresistant epilepsy. Despite medical advances, the current existing therapeutic strategies for pharmacoresistant seizure control are not available for all patients and/or present disadvantages. Moreover, the conventional drug therapies for psychiatric comorbidities have several adverse effects. Therefore, in this field, nanotechnology arises as a novel tool for transporting drugs to the brain under pathological conditions with high efficiency and low side effects. </p> <p> Objective: Present an overview of nanotechnology as a novel, efficient and enhanced therapeutic strategy for controlling pharmacoresistant epilepsy and its associated psychiatric comorbidities. </p> <p> Conclusion: Nanotechnology emerges as a powerful tool for the control and/or treatment of pharmacoresistant epilepsy and its comorbidities in a more efficient and safer way than conventional treatments.

Spinogenesis and Plastic Changes in the Dendritic Spines of Spinal Cord Motoneurons After Traumatic Injury in Rats.

BACKGROUND: Spinal cord injury (SCI) is highly incapacitating, and the neurobiological factors involved in an eventual functional recovery remain uncertain. Plastic changes to dendritic spines are closely related with the functional modifications of behavior. AIM OF THE STUDY: To explore the plastic response of dendritic spines in motoneurons after SCI. METHODS: Female rats were assigned to either of three groups: Intact (no manipulations), Sham (T9 laminectomy), and SCI (T9 laminectomy and spinal cord contusion). RESULTS: Motor function according to a BBBscale was progressively recovered from 2 week through 8 week postinjury, reaching a plateau through week 16. Dendritic spine density was greater in SCI vs. control groups, rostral as well as caudal to the lesion, at 8 and 16 weeks postinjury. Thin and stubby/wide spines were more abundant at both locations and time points, whereas mushroom spines predominated at 2 and 4 months in rostral to the lesion. Filopodia and atypical structures resembling dendritic spines were observed. Synaptophysin expression was lower in SCI at the caudal portion at 8 weeks, and was higher at week 16. CONCLUSION: Spinogenesis in spinal motoneurons may be a crucial plastic response to favor spontaneous recovery after SCI.

Enzyme activities involved in the glutamate-glutamine cycle are altered to reduce glutamate after spinal cord injury in rats.

Glutamate (Glu) neurotransmitter is involved in the excitotoxic damage after spinal cord injury (SCI). Glu is transformed into glutamine (Gln) by glutamine synthetase (GS) enzyme in glial cells. Once into the neurons, Gln is transformed back into Glu by phosphate-activated glutaminase (PAG). Glu is also a precursor for the synthesis of γ-aminobutyric acid through the action of the glutamic acid decarboxylase (GAD) enzyme. The contribution of all these Glu biotransformations after SCI has not been determined. The aim of this work is to characterize the role of GS, PAG, and GAD in the acute phase after SCI. Female Wistar rats were subjected to SCI by contusion and killed 2, 4, 8, and 12 h after surgery. Sham-injury animals, killed at the same time points served as controls. PAG and GAD activities were analyzed by high-performance liquid chromatography, whereas GS activity was determined by ultraviolet-visible spectroscopy. GS activity showed a significant decrease in animals with SCI at all time points evaluated versus the sham group. Similarly, the activity of the PAG was decreased at all time points compared with the control group. Finally, GAD activity was significantly increased in the SCI group when measured at 2, 4, and 8 h after lesion. The results of this study suggest that excitotoxicity is highly regulated through Glu/Gln and Glu/γ-aminobutyric acid cycles as an important mechanism to prevent further damage in the acute phase after lesion.