Alpha2-adrenergic receptor activation reinstates motor deficits in rats recovering from cortical injury.

Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride. Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor cortex injury. The aim of this study was to analyze the role of α2-adrenergic receptors in the restoration of motor deficits in recovering rats after brain damage. The rats were randomly assigned to the sham and injury groups and then treated with the following pharmacological agents at 3 hours before and 8 hours, 3 days, and 20 days after ferrous chloride-induced cortical injury: saline, clonidine, efaroxan (a selective antagonist of α2-adrenergic receptors) and clonidine + efaroxan. The sensorimotor score, the immunohistochemical staining for α2A-adrenergic receptors, and norepinephrine levels were evaluated. Eight hours post-injury, the sensorimotor score and norepinephrine levels in the locus coeruleus of the injured rats decreased, and these effects were maintained 3 days post-injury. However, 20 days later, clonidine administration diminished norepinephrine levels in the pons compared with the sham group. This effect was accompanied by sensorimotor deficits. These effects were blocked by efaroxan. In conclusion, an increase in α2-adrenergic receptor levels was observed after injury. Clonidine restores motor deficits in rats recovering from cortical injury, an effect that was prevented by efaroxan. The underlying mechanisms involve the stimulation of hypersensitive α2-adrenergic receptors and inhibition of norepinephrine activity in the locus coeruleus. The results of this study suggest that α2 receptor agonists might restore deficits or impede rehabilitation in patients with brain injury, and therefore pharmacological therapies need to be prescribed cautiously to these patients.

Absence of Neuroplastic Changes in the Bilateral H-Reflex Amplitude following Spinal Manipulation with Activator IV.

Background and Objectives: Chiropractic spinal manipulation is an alternative medical procedure for treating various spinal dysfunctions. Great interest exists in investigating its neuroplastic effects on the central nervous system. Previous studies have found contradictory results in relation to the neuroplastic changes in the H-reflex amplitude as a response to manual spinal manipulation. The discrepancies could be partly due to differences in the unilateral nature of these recordings and/or the variable force exerted in manual techniques applied by distinct chiropractors. Concerning the latter point, the variability in the performance of manual interventions may bias the determination of the significance of changes in H-reflex responses derived from spinal manipulation. To investigate such responses, a chiropractic device can be used to provide more precise and reproducible results. The current contribution aimed to examine whether spinal manipulation with an Activator IV instrument generates neuroplastic effects on the bilateral H-reflex amplitude in dancers and non-dancers. Materials and Methods: A radiograph verified spinal dysfunction in both groups of participants. Since there were significant differences between groups in the mean Hmax values of the H-reflex amplitude before spinal intervention, an assessment was made of the possible dependence of the effects of spinal manipulation with Activator IV on the basal conditions. Results: Ten sessions of spinal manipulation with Activator IV did not cause statistically significant changes in the bilateral H-reflex amplitude (measured as the Hmax/Mmax ratio) in either group. Furthermore, no significant difference was detected in the effects of spinal manipulation between groups, despite their distinct basal H-reflex amplitude. Conclusions: Regarding the therapeutic benefits of a chiropractic adjustment, herein carried out with Activator IV, the present findings suggest that the mechanism of action is not on the monosynaptic H-reflex pathway. Further research is needed to understand the mechanisms involved.

High Fructose and High Fat Diet Impair Different Types of Memory through Oxidative Stress in a Sex- and Hormone-Dependent Manner.

Metabolic syndrome (MetS) contributes to the spread of cardiovascular diseases, diabetes mellitus type 2, and neurodegenerative diseases. Evaluation of sex- and hormone-dependent changes in body weight, blood pressure, blood lipids, oxidative stress markers, and alterations in different types of memory in Sprague-Dawley rats fed with a high fat and high fructose (HFHF) diet were evaluated. After 12 weeks of feeding the male and female rats with HFHF, body weight gain, increase in blood pressure, and generation of dyslipidemia compared to the animals fed with chow diet were observed. Regarding memory, it was noted that gonadectomy reverted the effects of HFHF in the 24 h novel object recognition task and in spatial learning/memory analyzed through Morris water maze, males being more affected than females. Nevertheless, gonadectomy did not revert long-term memory impairment in the passive avoidance task induced by HFHF nor in male or female rats. On the other hand, sex-hormone-diet interaction was observed in the plasma concentration of malondialdehyde and nitric oxide. These results suggest that the changes observed in the memory and learning of MetS animals are sex- and hormone-dependent and correlate to an increase in oxidative stress.

Motor Recovery after Chronic Spinal Cord Transection in Rats: A Proof-of-Concept Study Evaluating a Combined Strategy.

BACKGROUND: The chronic phase of Spinal Cord (SC) injury is characterized by the presence of a hostile microenvironment that causes low activity and a progressive decline in neurological function; this phase is non-compatible with regeneration. Several treatment strategies have been investigated in chronic SC injury with no satisfactory results. OBJECTIVE- In this proof-of-concept study, we designed a combination therapy (Comb Tx) consisting of surgical glial scar removal plus scar inhibition, accompanied with implantation of mesenchymal stem cells (MSC), and immunization with neural-derived peptides (INDP). METHODS: This study was divided into three subsets, all in which Sprague Dawley rats were subjected to a complete SC transection. Sixty days after injury, animals were randomly allocated into two groups for therapeutic intervention: control group and animals receiving the Comb-Tx. Sixty-three days after treatment we carried out experiments analyzing motor recovery, presence of somatosensory evoked potentials, neural regeneration-related genes, and histological evaluation of serotoninergic fibers. RESULTS: Comb-Tx induced a significant locomotor and electrophysiological recovery. An increase in the expression of regeneration-associated genes and the percentage of 5-HT+ fibers was noted at the caudal stump of the SC of animals receiving the Comb-Tx. There was a significant correlation of locomotor recovery with positive electrophysiological activity, expression of GAP43, and percentage of 5-HT+ fibers. CONCLUSION: Comb-Tx promotes motor and electrophysiological recovery in the chronic phase of SC injury subsequent to a complete transection. Likewise, it is capable of inducing the permissive microenvironment to promote axonal regeneration.

The Complexity of H-wave Amplitude Fluctuations and Their Bilateral Cross-Covariance Are Modified According to the Previous Fitness History of Young Subjects under Track Training.

The Hoffmann reflex (H-wave) is produced by alpha-motoneuron activation in the spinal cord. A feature of this electromyography response is that it exhibits fluctuations in amplitude even during repetitive stimulation with the same intensity of current. We herein explore the hypothesis that physical training induces plastic changes in the motor system. Such changes are evaluated with the fractal dimension (FD) analysis of the H-wave amplitude-fluctuations (H-wave FD) and the cross-covariance (CCV) between the bilateral H-wave amplitudes. The aim of this study was to compare the H-wave FD as well as the CCV before and after track training in sedentary individuals and athletes. The training modality in all subjects consisted of running three times per week (for 13 weeks) in a concrete road of 5 km. Given the different physical condition of sedentary vs. athletes, the running time between sedentary and athletes was different. After training, the FD was significantly increased in sedentary individuals but significantly reduced in athletes, although there were no changes in spinal excitability in either group of subjects. Moreover, the CCV between bilateral H-waves exhibited a significant increase in athletes but not in sedentary individuals. These differential changes in the FD and CCV indicate that the plastic changes in the complexity of the H-wave amplitude fluctuations as well as the synaptic inputs to the Ia-motoneuron systems of both legs were correlated to the previous fitness history of the subjects. Furthermore, these findings demonstrate that the FD and CCV can be employed as indexes to study plastic changes in the human motor system.

Cyclosporin-A enhances non-functional axonal growing after complete spinal cord transection.

Therapeutic approaches that promote both neuroprotection and neuroregeneration would be valuable for spinal cord (SC) injury therapies. Cyclosporin-A (CsA) is an immunosuppressant that, due to its mechanism of action, could both protect and regenerate the neural tissue after injury. Previous studies have already demonstrated that intraperitoneal administration of CsA at a dose of 2.5 mg/kg/12 h during the first 2 days after SC contusion, followed by 5 mg/kg/12 h orally, diminishes tissue damage and improves motor recovery. In order to evaluate the effect of this CsA dosing regimen on axonal growth, we assessed motor recovery, presence of axons establishing functional connections and expression of GAP-43 in rats subjected to a complete SC transection. The Basso-Beattie-Bresnahan rating scale did not show difference in motor recovery of CsA or vehicle-treated rats. Moreover, somato-sensorial evoked potentials demonstrated no functional connections in the SC of these animals. Nevertheless, histological studies showed that: i) a significant number of CsA-treated rats presented growing axons, although they deviated perpendicularly at the edge of the stumps, surrounding them, ii) the expression of GAP-43 in animals treated with CsA was higher than that observed in the control group. Finally, anterograde tracing of the corticospinal tract of rats subjected to an incomplete SC transection showed no axonal fibers reaching the caudal stump. In summary, CsA administered at the dosing-regimen that promotes neuroprotection in SC contused rats induces both GAP-43 expression and axonal growth; however, it failed to generate functional connections in SC transected animals.

Absence of linear correlation between fluctuations in area of simultaneous recorded monosynaptic responses and Hoffmann's reflexes in the rat.

In this study we analyze the possible relationship between fluctuations in area of monosynaptic reflex responses (MSR) and Hoffmann's reflex (H reflexes) in the plantar closed loop pathway of the anesthetized rat. These reflexes were evoked by low-frequency stimuli applied to the sciatic nerve or lateral plantar nerve and then concurrently recorded on the distal tibial nerve or lateral plantar nerve, respectively as well as the lateral plantar muscles in the foot of the anesthetized rat. From trial to trial, H reflexes showed higher variability in area than MSR, whether the latter was recorded in the distal tibial nerve (n=8 experiments) or in the lateral plantar nerve (n=5 experiments). No linear correlation was found between changes in area of concurrently evoked MSR and H reflexes (r(MSR-H,n=8)=0.11+/-0.03 and r(MSR-H,n=5)=0.08+/-0.09, respectively). These findings suggest that trial-to-trial fluctuations in area of H reflexes may involve interaction of several sources of variation, among others to MSR variability (due to pre-, and post-synaptic factors influencing the excitability of spinal motoneurons) in combination with those related to peripheral mechanisms, such as trial to trial activation of a different number of muscle fibers, either by the probabilistic transmitter release from neuromuscular junctions, by activation of motor units of variable size or to fluctuations in excitability of muscle fibers.