Validation of the Nepali version of the Spinal Cord Independence Measure Self-Report
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Pathogenesis of aquatic bird bornavirus 1 in turkeys of different age
Aquatic bird bornavirus 1 (ABBV1), an orthobornavirus in the family Bornaviridae, displays a broad host range among avian species, including poultry. The pathogenesis of orthobornaviruses, at least in mammals and psittacines, appears to be mediated by the host immune response against the infected nervous tissue, with younger animals showing a milder disease due to immune tolerance. Here, we tested the ability of ABBV1 to infect domestic turkeys (Meleagris gallopavo), with a focus on evaluating the impact of age at infection. Cohorts of 6-week-old (old) and day-old (young) male turkeys were divided into virus-inoculated and control groups, and kept for up to 12 weeks. Results showed that turkeys of both ages were susceptible to ABBV1 infection by intramuscular administration, following a centripetal and limited centrifugal spread, although infection appeared delayed in old compared to young birds. Notably, only young turkeys developed clinical signs and more frequent inflammation of the central nervous system, indicating that infection at a very early age is unlikely to induce tolerance to ABBV1 infection.
Brainstem serotonin amplifies nociceptive transmission in a mouse model of Parkinson’s disease
Parkinson’s disease arises from the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as akinesia, rigidity, and tremor at rest. The non-motor component of Parkinson’s disease includes increased neuropathic pain, the prevalence of which is 4 to 5 times higher than the general rate. By studying a mouse model of Parkinson’s disease induced by 6-hydroxydopamine, we assessed the impact of dopamine depletion on pain modulation. Mice exhibited mechanical hypersensitivity associated with hyperexcitability of neurons in the dorsal horn of the spinal cord (DHSC). Serotonin (5-HT) levels increased in the spinal cord, correlating with reduced tyrosine hydroxylase (TH) immunoreactivity in the nucleus raphe magnus (NRM) and increased excitability of 5-HT neurons. Selective optogenetic inhibition of 5-HT neurons attenuated mechanical hypersensitivity and reduced DHSC hyperexcitability. In addition, the blockade of 5-HT2A and 5-HT3 receptors reduced mechanical hypersensitivity. These results reveal, for the first time, that PD-like dopamine depletion triggers spinal-mediated mechanical hypersensitivity, associated with serotonergic hyperactivity in the NRM, opening up new therapeutic avenues for Parkinson’s disease-associated pain targeting the serotonergic systems.
The clinical evolution of patients with idiopathic spinal cord herniation: a case series
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AAV1.NT3 gene therapy mitigates the severity of autoimmune encephalomyelitis in the mouse model for multiple sclerosis
Multiple sclerosis (MS) is an immune-mediated chronic inflammatory and neurodegenerative disease of the central nervous system (CNS) affecting more than 2.5 million patients worldwide. Chronic demyelination in the CNS has an important role in perpetuating axonal loss and increases difficulty in promoting remyelination. Therefore, regenerative, and neuroprotective strategies are essential to overcome this impediment to rescue axonal integrity and function. Neurotrophin 3 (NT-3) has immunomodulatory and anti-inflammatory properties, in addition to its well-recognized function in nervous system development, myelination, neuroprotection, and regeneration. For this study, scAAV1.tMCK.NT-3 was delivered to the gastrocnemius muscle of experimental autoimmune encephalomyelitis (EAE) mice, the chronic relapsing mouse model of MS, at 3 weeks post EAE induction. Measurable NT-3 levels were found in serum at 7-weeks post gene delivery. The treated cohort showed improved clinical scores and performed significantly better in rotarod, and grip strength tests compared to their untreated counterparts. Histopathologic studies showed improved remyelination and axon protection. These data correlated with reduced expression of the pro-inflammatory cytokines in brain and spinal cord, and increased percentage of regulatory T cells in the spleens and lymph nodes. Collectively, these findings demonstrate the translational potential of AAV-delivered NT-3 for chronic progressive MS.
Modulating neuroplasticity for chronic pain relief: noninvasive neuromodulation as a promising approach
Chronic neuropathic pain is a debilitating neuroplastic disorder that notably impacts the quality of life of millions of people worldwide. This complex condition, encompassing various manifestations, such as sciatica, diabetic neuropathy and postherpetic neuralgia, arises from nerve damage or malfunctions in pain processing pathways and involves various biological, physiological and psychological processes. Maladaptive neuroplasticity, known as central sensitization, plays a critical role in the persistence of chronic neuropathic pain. Current treatments for neuropathic pain include pharmacological interventions (for example, antidepressants and anticonvulsants), invasive procedures (for example, deep brain stimulation) and physical therapies. However, these approaches often have limitations and potential side effects. In light of these challenges, interest in noninvasive neuromodulation techniques as alternatives or complementary treatments for neuropathic pain is increasing. These methods aim to induce analgesia while reversing maladaptive plastic changes, offering potential advantages over conventional pharmacological practices and invasive methods. Recent technological advancements have spurred the exploration of noninvasive neuromodulation therapies, such as repetitive transcranial magnetic stimulation, transcranial direct current stimulation and transcranial ultrasound stimulation, as well as innovative transformations of invasive techniques into noninvasive methods at both the preclinical and clinical levels. Here this review aims to critically examine the mechanisms of maladaptive neuroplasticity in chronic neuropathic pain and evaluate the efficacy of noninvasive neuromodulation techniques in pain relief. By focusing on optimizing these techniques, we can better assess their short-term and long-term effects, refine treatment variables and ultimately improve the quality of neuropathic pain management.
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