Comments on Intracellular Studies of Presynaptic Inhibition

The use of intracellular electrodes, e.g., (micropipettes), in electrophysiological studies of the central nervous system, has enhanced our understanding of the basic function of the nervous system. The purpose of this paper is to review a study in which this microtechnique was successfully employed in the spinal cord

Spinal neurons that contain gastrin-releasing peptide seldom express Fos or phosphorylate extracellular signal-regulated kinases in response to intradermal chloroquine

Background: Gastrin-releasing peptide (GRP) is thought to play a role in the itch evoked by intradermal injection of chloroquine. Although some early studies suggested that GRP was expressed in pruriceptive primary afferents, it is now thought that GRP in the spinal cord is derived mainly from a population of excitatory interneurons in lamina II, and it has been suggested that these are involved in the itch pathway. To test this hypothesis, we used the transcription factor Fos and phosphorylation of extracellular signal-regulated kinases (ERK) to look for evidence that interneurons expressing GRP were activated following intradermal injection of chloroquine into the calf, in mice that express enhanced green fluorescent protein (EGFP) in these cells. Results: Injection of chloroquine resulted in numerous Fos- or phospho-ERK (pERK) positive cells in the somatotopically appropriate part of the superficial dorsal horn. The proportion of all neurons in this region that showed Fos or pERK was 18% and 21%, respectively. However, among the GRP–EGFP, only 7% were Fos-positive and 3% were pERK-positive. As such, GRP–EGFP cells were significantly less likely than other neurons to express Fos or to phosphorylate ERK. Conclusions: Both expression of Fos and phosphorylation of ERK can be used to identify dorsal horn neurons activated by chloroquine injection. However, these results do not support the hypothesis that interneurons expressing GRP are critical components in the itch pathway

On the origin of F-wave: involvement of central synaptic mechanisms

Neurophysiological methods are used widely to gain information about motor neuron excitability and axon conduction in neurodegenerative diseases. The F-wave is a common biomarker used to test motor neuron properties in the diagnosis of neurological diseases. Although the origin of the F-wave is a subject of debate, the most widely accepted mechanism posits that the F-wave is generated by the backfiring of motor neurons stimulated antidromically from the periphery. In this study, we developed an ex vivo mouse sciatic nerve-attached spinal cord preparation with sensory axons severed. In this preparation, stimulation of the whole sciatic nerve or its tibial branch evoked responses with the electrophysiological signatures of F-waves. Manipulations of synaptic transmission by either removal of extracellular calcium or block of post-synaptic glutamate receptors abolished these responses. These results suggest that F-waves are mediated by spinal microcircuits activated by recurrent motor axon collaterals via glutamatergic synapses

PTEN inhibitor bisperoxovanadium protects oligodendrocytes and myelin and prevents neuronal atrophy in adult rats following cervical hemicontusive spinal cord injury

Cervical spinal cord injury (SCI) damages axons and motor neurons responsible for ipsilateral forelimb function and causes demyelination and oligodendrocyte death. Inhibition of the phosphatase and tensin homologue, PTEN, promotes neural cell survival, neuroprotection and regeneration in vivo and in vitro. PTEN inhibition can also promote oligodendrocyte-mediated myelination of axons in vitro likely through Akt activation. We recently demonstrated that acute treatment with phosphatase PTEN inhibitor, bisperoxovanadium (bpV)-pic reduced tissue damage, neuron death, and promoted functional recovery after cervical hemi-contusion SCI. Evidence suggests bpV can promote myelin stability; however, bpV effects on myelination and oligodendrocytes in contusive SCI models are unclear. We hypothesized that bpV could increase myelin around the injury site through sparing or remyelination, and that bpV treatment may promote increased numbers of oligodendrocytes. Using histological and immunofluorescence labeling, we found that bpV treatment promoted significant spared white matter (30%; p < 0.01) and Luxol Fast Blue (LFB)+ myelin area rostral (Veh: 0.56 ± 0.01 vs. bpV: 0.64 ± 0.02; p < 0.05) and at the epicenter (Veh: 0.4175 ± 0.03 vs. bpV: 0.5400 ± 0.03; p < 0.05). VLF oligodendrocytes were also significantly greater with bpV therapy (109 ± 5.3 vs. Veh: 77 ± 2.7/mm2; p < 0.01). In addition, bpV increased mean motor neuron soma area versus vehicle-treatment (1.0 ± 0.02 vs. Veh: 0.77 ± 0.02) relative to Sham neuron size. This study provides key insight into additional cell and tissue effects that could contribute to bpV-mediated functional recovery observed after contusive cervical SCI

Phosphorylation of ERK in neurokinin 1 receptor-expressing neurons in laminae III and IV of the rat spinal dorsal horn following noxious stimulation

BACKGROUND: There is a population of large neurons with cell bodies in laminae III and IV of the spinal dorsal horn which express the neurokinin 1 receptor (NK1r) and have dendrites that enter the superficial laminae. Although it has been shown that these are all projection neurons and that they are innervated by substance P-containing (nociceptive) primary afferents, we know little about their responses to noxious stimuli. In this study we have looked for phosphorylation of extracellular signal-regulated kinases (ERKs) in these neurons in response to different types of noxious stimulus applied to one hindlimb of anaesthetised rats. The stimuli were mechanical (repeated pinching), thermal (immersion in water at 52°C) or chemical (injection of 2% formaldehyde). RESULTS: Five minutes after each type of stimulus we observed numerous cells with phosphorylated ERK (pERK) in laminae I and IIo, together with scattered positive cells in deeper laminae. We found that virtually all of the lamina III/IV NK1r-immunoreactive neurons contained pERK after each of these stimuli and that in the great majority of cases there was internalisation of the NK1r on the dorsal dendrites of these cells. In addition, we also saw neurons in lamina III that were pERK-positive but lacked the NK1r, and these were particularly evident in animals that had had the pinch stimulus. CONCLUSION: Our results demonstrate that lamina III/IV NK1r-immunoreactive neurons show receptor internalisation and ERK phosphorylation after mechanical, thermal or chemical noxious stimuli

Molecular and cellular aspects of plasticity after neural injury

This review focuses on our effort to address plasticity of the nervous system after neural injury. We have used different animal models to examine cellular mechanisms of plasticity underlying the pathological and repair processes. After severance of sensory input from one inner ear, topographic representations of spacecentered coordinates in the brain undergo plastic changes. During vestibular compensation, tissue plasticity constitutes an important component for functional recovery of neuronal network. In Parkinsonian animals, modulation of signaling via glutamatergic synapses, neurotrophins and neurokinins contributes to the protection of basal ganglion neurons from degeneration, thereby delaying deterioration of motor functions. With the use of animal models of neural injury, we further overcome the molecular restriction at the glial scar to enhance neural regrowth and remyelination, pointing to the possibility of developing new therapeutic strategies to stimulate neural plasticity and repair in the adult nervous system.published_or_final_versio

The Effect of Music Therapy on Anxiety and Vital Signs of Patients with Acute Coronary Syndrome: A Study in the Cardiac Care Unit of Vali-Asr Hospital, Eghlid, Iran

Background: Acute coronary syndrome is an emergency situation, characterized by a sudden decrease of blood flow to the heart and chest pain during a heart attack or unstable angina. High levels of anxiety increases mortality risk up to three times. The aim of this study was to determine the effect of music therapy on anxiety level and vital signs of patients with acute coronary syndrome admitted in the coronary care unit of Vali- Asr hospital, in Eghlid city. Methods: This clinical trial was conducted on 70 acute coronary syndrome patients who were eligible for the study during 2011-2012. Anxiety level was measured by the standard Spielberger Questionnaire and vital signs of patients were recorded before and after the intervention. Data were analyzed through SPSS18 and using mean, percentage, standard deviation, independent and paired t- test. Results: Music had no effect on vital signs but significantly reduced anxiety level (P=0.049). Anxiety was significantly higher in females, but showed no significant relationship with age and education. There was no significant relationship between age, sex and education with respiratory rate, heart rate and systolic or diastolic blood pressure. Conclusions: Music as an easy and low cost intervention without any complication can be used to reduce anxiety in patients in Coronary Care Units

Left Main Stem Percutaneous Coronary Intervention: Does On-Site Surgical Cover Make a Difference?

BACKGROUND: Nonsurgical centers (NSC) contribute significantly to the capacity of overall percutaneous coronary intervention (PCI) in the United Kingdom. Although previous studies have demonstrated similar PCI outcomes in surgical centers (SC) versus NSC, it is unknown whether this applies to more complex procedures such as left main stem (LMS) PCI. We compared patient characteristics and outcomes of LMS PCI performed across SC and NSC in England and Wales. METHODS: A retrospective analysis of procedures between January 2006 and March 2020 was performed using the British Cardiovascular Intervention Society database and stratified according to the surgical status of the center. The primary outcomes assessed were in-hospital major adverse cardiovascular and cerebrovascular events, all-cause mortality, and Bleeding Academic Research Consortium stage 3 to 5 bleeding. RESULTS: Forty thousand seven hundred forty-four patients underwent LMS PCI during the period, of which 13?922 (34.2%) had their procedure performed at an NSC. The proportion of LMS PCI performed in NSC increased >2-fold (15.9% in 2006 to 36.7% in 2020). There was no association between surgical cover location and in-hospital mortality (odds ratio, 0.92 [95% CI, 0.69-1.22]), in-hospital major adverse cardiovascular and cerebrovascular events (odds ratio, 1.00 [95% CI, 0.79-1.25]), or emergency coronary artery bypass graft surgery (odds ratio, 1.00 [95% CI, 0.95-1.06]). NSC had lower Bleeding Academic Research Consortium 3 to 5 bleeding complications (odds ratio, 0.53 [95% CI, 0.34-0.82]). CONCLUSIONS: There has been an increase in LMS PCI volumes at NSC, particularly elective LMS PCI. LMS PCI performed at NSC was not associated with increased mortality, in-hospital major adverse cardiovascular and cerebrovascular events, or emergency coronary artery bypass graft surgery, despite higher disease complexity

Charcot osteoarthropathy: one disease, two presentations

Charcot osteoarthropathy or Charcot foot is a disabling complication of diabetes and is associated with poor prognosis and high mortality. Its pathogenesis is not fully understood and its treatment is at best symptomatic. Furthermore, it is not known whether there is a specific type of neuropathy which affects osteoclastic activity, and thereby leads to reduction of bone mineral density and the development of Charcot osteoarthropathy. Recently it has been proposed that there is a difference in the presentation of Charcot osteoarthropathy between type 1 and type 2 diabetes. This article reviews the link between underlying osteopenia, abnormal biomechanical forces and type of neuropathy, and their varying interaction in the pathogenesis of Charcot osteoarthropathy in type 1 and type 2 diabetes. Further attention is drawn to the newly discovered osteoprotegerin/receptor activator of nuclear factor kappaB ligand (OPG/RANKL) cytokine system, which controls bone resorption. Increased osteoclastic activity in the acute Charcot foot may be associated with altered expression of OPG/RANKL signaling pathway and modulation of the OPG/RANKL equilibrium in Charcot osteoarthropathy may provide additional therapeutical option to manage this difficult condition.Biomedical Reviews 2005; 16: 43-48