Automated Mechanical Peripheral Stimulation Effects on Gait Variability in Individuals With Parkinson Disease and Freezing of Gait: A Double-Blind,Randomized Controlled Trial

Objective

To assess the effects of automated peripheral stimulation (AMPS) in reducing gait variability of subjects with Parkinson disease (PD) and freezing of gait (FOG) treated with AMPS and to explore the effects of this treatment on gait during a single task (walking) and a dual task (walking while attending the word-color Stroop test).

Adenosine A2A receptors are necessary and sufficient to trigger memory impairment in adult mice

Background and Purpose

Caffeine (a non-selective adenosine receptor antagonist) prevents memory deficits in aging and Alzheimer’s disease, an effect mimicked by adenosine A_2A receptor, but not A₁ receptor, antagonists. Hence, we investigated the effects of adenosine receptor agonists and antagonists on memory performance and scopolamine-induced memory impairment in mice.

Experimental Approach

We determined whether A_2A receptors are necessary for the emergence of memory impairments induced by scopolamine and whether A_2A receptor activation triggers memory deficits in naïve mice, using three tests to assess short-term memory, namely the object recognition task, inhibitory avoidance and modified Y-maze.

Key Results

Scopolamine (1.0 mg·kg⁻¹, i.p.) impaired short-term memory performance in all three tests and this scopolamine-induced amnesia was prevented by the A_2A receptor antagonist (SCH 58261, 0.1–1.0 mg·kg⁻¹, i.p.) and by the A₁ receptor antagonist (DPCPX, 0.2–5.0 mg·kg⁻¹, i.p.), except in the modified Y-maze where only {"type":"entrez-protein","attrs":{"text":"SCH58261","term_id":"1052882304"}}SCH58261 was effective. Both antagonists were devoid of effects on memory or locomotion in naïve rats. Notably, the activation of A_2A receptors with CGS 21680 (0.1–0.5 mg·kg⁻¹, i.p.) before the training session was sufficient to trigger memory impairment in the three tests in naïve mice, and this effect was prevented by SCH 58261 (1.0 mg·kg⁻¹, i.p.). Furthermore, i.c.v. administration of CGS 21680 (50 nmol) also impaired recognition memory in the object recognition task.

Conclusions and Implications

These results show that A_2A receptors are necessary and sufficient to trigger memory impairment and further suggest that A₁ receptors might also be selectively engaged to control the cholinergic-driven memory impairment.     

Overcoming obstacles: nerve-sparing issues in radical prostatectomy

PURPOSE: To review, compare, and contrast recovery of potency after robot-assisted radical prostatectomy with specific regard to thermal and excisional nerve injury. Our goal was to compare intensity of injury and ability to recover potency in order to stratify risk by injury type. METHODS: We compare potency outcomes in our first 500 consecutive cases of robot-assisted radical prostatectomy. This is a retrospective review of data collected prospectively into an electronic database. Preoperative inclusion criteria were age less than 66 years, International Index of Erectile Function Score of 22-25, and unilateral or bilateral nerve preservation. Potency data were collected via patient-reported validated questionnaires. Potency was defined with two affirmative responses to: "erections hard enough for sexual intercourse" and were they "satisfactory." Results were collated and graphically analyzed so that time-line comparisons of recovery could be evaluated. RESULTS: Time-line curves were generated comparing recovery of sexual function over 2 years after nervesparing techniques using cautery versus cautery-free and unilateral versus bilateral nerve preservation. Use of no cautery improved early return of sexual function 4.7-fold over cautery. Whether using cautery or cautery-free techniques, a doubling of nerve tissue from one nerve to two nerves spared only resulted in a 1.2-fold improvement of potency recovery both early and long-term. CONCLUSIONS: In our experience, avoidance of thermal injury produces nearly a 5-fold improvement in early return of sexual function. Furthermore, thermal injury appears to induce a dense but largely recoverable injury after 2 years. In contrast to common belief, our results demonstrated that preservation of just one nerve will, in the majority of patients, result in similar potency recovery to that with two nerves preserved. Crossover innervation of the one nerve is favored over compensation and hints that techniques that increase nerve volume at the expense of positive surgical margins may need careful introspection.     

Effect of skilled and unskilled training on nerve regeneration and functional recovery

The most disabling aspect of human peripheral nerve injuries, the majority of which affect the upper limbs, is the loss of skilled hand movements. Activity-induced morphological and electrophysiological remodeling of the neuromuscular junction has been shown to influence nerve repair and functional recovery. In the current study, we determined the effects of two different treatments on the functional and morphological recovery after median and ulnar nerve injury. Adult Wistar male rats weighing 280 to 330 g at the time of surgery (N = 8-10 animals/group) were submitted to nerve crush and 1 week later began a 3-week course of motor rehabilitation involving either “skilled” (reaching for small food pellets) or “unskilled” (walking on a motorized treadmill) training. During this period, functional recovery was monitored weekly using staircase and cylinder tests. Histological and morphometric nerve analyses were used to assess nerve regeneration at the end of treatment. The functional evaluation demonstrated benefits of both tasks, but found no difference between them (P > 0.05). The unskilled training, however, induced a greater degree of nerve regeneration as evidenced by histological measurement (P < 0.05). These data provide evidence that both of the forelimb training tasks used in this study can accelerate functional recovery following brachial plexus injury.     

An ultrastructural study of cell death in the CA1 pyramidal field of the hippocapmus in rats submitted to transient global ischemia followed by reperfusion

In the course of ischemia and reperfusion a disruption of release and uptake of excitatory neurotransmitters occurs. This excitotoxicity triggers delayed cell death, a process closely related to mitochondrial physiology and one that shows both apoptotic and necrotic features. The aim of the present study was to use electron microscopy to characterize the cell death of pyramidal cells from the CA1 field of the hippocampus after 10 min of transient global ischemia followed by short reperfusion periods. For this study 25 adult male Wistar rats were used, divided into six groups: 10 min of ischemia, 3, 6, 12 and 24 h of reperfusion and an untouched group. Transient forebrain ischemia was produced using the 4-vessel occlusion method. The pyramidal cells of the CA1 field from rat hippocampus submitted to ischemia exhibited intracellular alterations consistent with a process of degeneration, with varied intensities according to the reperfusion period and bearing both apoptotic and necrotic features. Gradual neuronal and glial modifications allowed for the classification of the degenerative process into three stages: initial, intermediate and final were found. With 3 and 6 h of reperfusion, slight and moderate morphological alterations were seen, such as organelle and cytoplasm edema. Within 12 h of reperfusion, there was an apparent recovery and more 'intact' cells could be identified, while 24 h after the event neuronal damage was more severe and cells with disrupted membranes and cell debris were identified. Necrotic-like neurons were found together with some apoptotic bodies with 24 h of reperfusion. Present results support the view that cell death in the CA1 field of rat hippocampus submitted to 10 min of global transient ischemia and early reperfusion times includes both apoptotic and necrotic features, a process referred to as parapoptosis.     

Pro-angiogenic effects of resveratrol in brain endothelial cells: nitric oxide-mediated regulation of vascular endothelial growth factor and metalloproteinases

Resveratrol may be a powerful way of protecting the brain against a wide variety of stress and injury. Recently, it has been proposed that resveratrol not only reduces brain injury but also promotes recovery after stroke. But the underlying mechanisms are unclear. Here, we tested the hypothesis that resveratrol promotes angiogenesis in cerebral endothelial cells and dissected the signaling pathways involved. Treatment of cerebral endothelial cells with resveratrol promoted proliferation, migration, and tube formation in Matrigel assays. Consistent with these pro-angiogenic responses, resveratrol altered endothelial morphology resulting in cytoskeletal rearrangements of β-catenin and VE-cadherin. These effects of resveratrol were accompanied by activation of phosphoinositide 3 kinase (PI3-K)/Akt and Mitogen-Activated Protein Kinase (MAPK)/ERK signaling pathways that led to endothelial nitric oxide synthase upregulation and increased nitric oxide (NO) levels. Subsequently, elevated NO signaling increased vascular endothelial growth factor and matrix metalloproteinase levels. Sequential blockade of these signaling steps prevented resveratrol-induced angiogenesis in cerebral endothelial cells. These findings provide a mechanistic basis for the potential use of resveratrol as a candidate therapy to promote angiogenesis and neurovascular recovery after stroke.     

Noninvasive Brain Stimulation Improves Hemispatial Neglect After Stroke: A Systematic Review and Meta-Analysis

Objective

To evaluate the effectiveness of noninvasive brain stimulation (NIBS)—repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS)—on hemispatial neglect and performance in activities of daily living (ADL) after stroke.