Restorative neurology and neuroscience最新文献

Background: Peripheral nerve injury (PNI) is the most common type of nerve trauma yet, while injured motoneurons exhibit a robust capacity for regeneration, behavioral recovery is protracted and typically poor. Neurotherapeutic approaches to PNI and repair have primarily focused on the enhancement of axonal regeneration, in terms of rate, axonal sprouting, and reconnection connectivity. Both electrical stimulation (ES) and treatment with androgens [e.g., testosterone propionate (TP)] have been demonstrated to enhance axonal sprouting, regeneration rate and functional recovery following PNI. To date, very little work has been done to examine the effects of ES and/or TP on dendritic morphology and organization within the spinal cord after PNI.

Objective: The objective of the current study was to examine the impact of treatment with TP and ES, alone or in combination, on the dendritic arbor of spinal motoneurons after target disconnection via sciatic nerve crush injury in the rat.

Methods: Rats received a crush injury to the sciatic nerve. Following injury, some animals received either (1) no further treatment beyond implantation with empty Silastic capsules, (2) electrical nerve stimulation immediately after injury, (3) implantation with Silastic capsules filled with TP, or (4) electrical nerve stimulation immediately after injury as well as implantation with TP. All of these groups of axotomized animals also received bi-weekly electromyography (EMG) testing. Additional groups of intact untreated animals as well as a group of injured animals who received no further treatment or EMG testing were also included. Eight weeks after injury, motoneurons innervating the anterior tibialis muscle were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions.

Results: After nerve crush and ES and/or TP treatment, motoneurons innervating the anterior tibialis underwent marked dendritic hypertrophy. Surprisingly, this dendritic hypertrophy occurred in all animals receiving repeated bi-weekly EMG testing, regardless of treatment. When the EMG testing was eliminated, the dendritic arbor extent and distribution after nerve crush in the treated groups did not significantly differ from intact untreated animals.

Conclusions: The ability of repeated EMG testing to so dramatically affect central plasticity following a peripheral nerve injury was unexpected. It was also unexpected that gonadal steroid hormones and/or ES, two neurotherapeutic approaches with demonstrated molecular/behavioral changes consistent with peripheral improvements in axonal repair and target reconnection, do not appear to impact central plasticity in a similar manner. The significance of peripheral EMG testing and resulting central plasticity reorganization remains to be determined.

Background: Cognitive dysfunctions after a brain stroke have a huge impact on patients' disability and activities of daily living. Prism adaptation (PA) is currently used in patients with right brain damage to improve lateralized spatial attentional deficits. Recent findings suggest that PA could also be useful for rehabilitation of other cognitive functions.

Objective: In the present study, we tested for the efficacy on cognitive rehabilitation of a novel device in which the procedure of prism adaptation is digitized and followed by cognitive training of attention and executive functions using serious games.

Methods: Thirty stroke patients were randomly assigned to two groups: an experimental group of 15 patients, which performed the experimental rehabilitation training using the novel device in 10 consecutive daily sessions; a control group of 15 patients, which performed the routine cognitive training in 10 consecutive daily sessions. Both groups were tested before and after the rehabilitation program on neuropsychological tests (digit and spatial span forward and backward, attentional matrices, Stroop task) and on functional scales (Barthel index and Beck Anxiety Index).

Results: The main results showed that only patients who received the experimental rehabilitation training improved their scores on tests of digit span forward, spatial span backward, attentional matrices and Stroop. Moreover, patients of the experimental but not of the control group showed a significant correlation between improvement on some tasks (mainly spatial span backward) and improvement on activities of daily living as well as with reduction of anxiety levels.

Conclusions: These results suggest that combining digital PA with cognitive training using serious games may be added in clinical settings for cognitive rehabilitation of stroke patients, with beneficial effects extending in promoting independency in activities of daily living and reduction of psychiatric symptoms.

Background: The hippocampus is highly vulnerable to damage in the brain ischemia-reperfusion injury model. Leuprolide acetate has been shown to promote neurological recovery after injury in various regions of the central nervous system.

Objective: The objective of this study was to assess the histology of the hippocampus and the expression of neuronal recovery markers, specifically the 200 kDa neurofilaments and the myelin basic protein, in rats with brain ischemia-reperfusion injury treated with leuprolide acetate.

Methods: The rats were divided into three groups: Sham, ischemia-reperfusion with saline solution, and ischemia-reperfusion treated with leuprolide acetate. Coronal brain slices were obtained and stained with hematoxylin-eosin. The histological analysis involved quantifying the number of neurons in the hippocampal regions CA1, CA3 and DG. The myelin basic protein and neurofilaments were quantified using western blot.

Results: The number of neurons in CA1 and DG was significantly higher in the leuprolide acetate group compared to the untreated group. Additionally, the expression of neurofilament and myelin basic protein markers was significantly increased in rats treated with leuprolide acetate compared to the untreated rats.

Conclusions: Leuprolide acetate promotes the recovery of hippocampal neurons in an acute brain ischemia-reperfusion injury model. These findings suggest that leuprolide acetate could be a potential therapeutic intervention for reversing damage in hippocampal ischemic lesions.

Background: The default mode network (DMN) is a large-scale brain network tightly correlated with self and self-referential processing, activated by intrinsic tasks and deactivated by externally-directed tasks.

Objective: In this study, we aim to investigate the novel approach of default mode activation during progressive muscle relaxation and examine whether differential activation patterns result from the movement of different body parts.

Methods: We employed neuroimaging to investigate DMN activity during simple body movements, while performing progressive muscle relaxation. We focused on differentiating the neural response between facial movements and movements of other body parts.

Results: Our results show that the movement of different body parts led to deactivation in several DMN nodes, namely the temporal poles, hippocampus, medial prefrontal cortex (mPFC), and posterior cingulate cortex. However, facial movement induced an inverted and selective positive BOLD pattern in some of these areas precisely. Moreover, areas in the temporal poles selective for face movement showed functional connectivity not only with the hippocampus and mPFC but also with the nucleus accumbens.

Conclusions: Our findings suggest that both conceptual and embodied self-related processes, including body movements during progressive muscle relaxation, may be mapped onto shared brain networks. This could enhance our understanding of how practices like PMR influence DMN activity and potentially offer insights to inform therapeutic strategies that rely on mindful body movements.

Background: Pharmacological treatments for ischemic stroke remain limited to thrombolysis, which is associated with increased risk of potentially fatal hemorrhage. Treatments with Recombinant Human Fibroblast Growth Factor 18 (rhFGF18) and Growth and Differentiation Factor 11 (rhGDF11) appear promising based on different preclinical models. The goal of this study was to compare the effects of rhFGF18 and rhGDF11 directly on survival, behavioral deficits, and histological fingerprint of cerebral ischemia in the Wistar rat middle cerebral artery occlusion (MCAO) model of stroke.

Methods: Ischemia-reperfusion injury was induced using a 2-hour transient MCAO. Animals were administered rhFGF18 (infusion), rhGDF11 (multi-injection), or Phosphate Buffered Saline (PBS) vehicle control and followed for 42 days. Motor-Cognitive deficits were evaluated using the Morris Water Maze at Days 0 (pre-MCAO), 7, 21, and 42. Histopathological assessments were performed on Days 21 and 42.

Results: Day 7 post-ischemia water maze performance times increased 38.3%, 2.1%, and 23.1% for PBS, rhFGF18, and rhGDF11-treated groups, respectively. Fraction of neurons with abnormal morphology (chromatolysis, pyknotic nuclei, somal degeneration) decreased in all groups toward Day 42 and was lowest for rhFGF18. AChE-positive fiber density and activity increased over time in the rhFGF18 group, remained unchanged in the rhGDF11 treatment arm, and declined in the PBS control. Metabolic increases were greatest in rhGDF11 treated animals, with both rhFGF18 and rhGDF11 achieving improvements over PBS, as evidenced by increased succinate dehydrogenase and lactate dehydrogenase activity. Finally, rhFGF18 treatment exhibited a trend for reduced mortality relative to PBS (5.6%, 95% CI [27.3%, 0.1% ] vs. 22.2%, 95% CI [47.6%, 6.4% ]).

Conclusions: rhFGF18 treatment appears promising in improving survival and promoting motor-cognitive recovery following cerebral ischemia-reperfusion injury.