Volume 35, Issue 3

Computational modeling helps neuroscientists to integrate and explain experimental data obtained through neurophysiological and anatomical studies, thus providing a mechanism by which we can better understand and predict the principles of neural computation. Computational modeling of the neuronal pathways of the visual cortex has been successful in developing theories of biological motion processing. This review describes a range of computational models that have been inspired by neurophysiological experiments. Theories of local motion integration and pattern motion processing are presented, together with suggested neurophysiological experiments designed to test those hypotheses.

Clinical studies have shown that individuals with spinal cord injury (SCI) are particularly susceptible to infectious diseases, resulting in a syndrome called SCI-induced immunodeficiency syndrome (SCI-IDS), which is the leading cause of death after SCI. It is believed that SCI-IDS is associated with exaggerated activation of sympathetic preganglionic neurons (SPNs). After SCI, disruption of bulbospinal projections from the medulla oblongata C1 neurons to the SPNs results in the loss of sympathetic inhibitory modulation from the brain and brainstem and the occurrence of abnormally high levels of spinal sympathetic reflexes (SSR), named sympathetic hyperreflexia. As the post-injury survival time lengthens, mass recruitment and anomalous sprouting of excitatory interneurons within the spinal cord result in increased SSR excitability, resulting in an excess sympathetic output that disrupts the immune response. Therefore, we first analyze the structural underpinnings of the spinal cord-sympathetic nervous system-immune system after SCI, then demonstrate the progress in highlighting mechanisms of SCI-IDS focusing on norepinephrine (NE)/Beta 2-adrenergic receptor (β2-AR) signal pathways, and summarize recent preclinical studies examining potential means such as regulating SSR and inhibiting β2-AR signal pathways to improve immune function after SCI. Finally, we present research perspectives such as to promote the effective regeneration of C1 neurons to rebuild the connection of C1 neurons with SPNs, to regulate excitable or inhibitory interneurons, and specifically to target β2-AR signal pathways to re-establish neuroimmune balance. These will help us design effective strategies to reverse post-SCI sympathetic hyperreflexia and improve the overall quality of life for individuals with SCI.

Myelination of axons in the central nervous system offers numerous advantages, including decreased energy expenditure for signal transmission and enhanced signal speed. The myelin sheaths surrounding an axon consist of a multi-layered membrane that is formed by oligodendrocytes, while specific glycoproteins and lipids play various roles in this formation process. As beneficial as myelin can be, its dysregulation and degeneration can prove detrimental. Inflammation, oxidative stress, and changes in cellular metabolism and the extracellular matrix can lead to demyelination of these axons. These factors are hallmark characteristics of certain demyelinating diseases including multiple sclerosis. The effects of demyelination are also implicated in primary degeneration in diseases such as glaucoma and Alzheimer’s disease, as well as in processes of secondary degeneration. This reveals a relationship between myelin and secondary processes of neurodegeneration, including resultant degeneration following traumatic injury and transsynaptic degeneration. The role of myelin in primary and secondary degeneration is also of interest in the exploration of strategies and targets for remyelination, including the use of anti-inflammatory molecules or nanoparticles to deliver drugs. Although the use of these methods in animal models of diseases have shown to be effective in promoting remyelination, very few clinical trials in patients have met primary end points. This may be due to shortcomings or considerations that are not met while designing a clinical trial that targets remyelination. Potential solutions include diversifying disease targets and requiring concomitant interventions to promote rehabilitation.

Association between vestibular function and immune inflammatory response has garnered increasing interest. Immune responses can lead to anatomical or functional alterations of the vestibular system, and inflammatory reactions may impair hearing and balance. Vestibular disorders comprise a variety of conditions, such as vestibular neuritis, benign paroxysmal positional vertigo, Meniere’s disease, vestibular migraine, posterior circulation ischemia, and bilateral vestibular disease. Moreover, some patients with autoimmune diseases develop vestibulocochlear symptom. This paper offers an overview of prevalent vestibular diseases and discusses associations between vestibular dysfunction and immune diseases.

Age-related macular degeneration (AMD) is a complex, multifactorial disease leading to progressive and irreversible retinal degeneration, whose pathogenesis has not been fully elucidated yet. Due to the complexity and to the multiple features of the disease, many efforts have been made to develop animal models which faithfully reproduce the overall AMD hallmarks or that are able to mimic the different AMD stages. In this context, light damage (LD) rodent models of AMD represent a suitable and reliable approach to mimic the different AMD forms (dry, wet and geographic atrophy) while maintaining the time-dependent progression of the disease. In this review, we comprehensively reported how the LD paradigms reproduce the main features of human AMD. We discuss the capability of these models to broaden the knowledge in AMD research, with a focus on the mechanisms and the molecular hallmarks underlying the pathogenesis of the disease. We also critically revise the remaining challenges and future directions for the use of LD models.

Oxidative stress (OS) and inflammation play a key role in the development of hypoxic–ischemic (H–I) induced brain damage. Following H–I, rapid neuronal death occurs during the acute phase of inflammation, and activation of the oxidant–antioxidant system contributes to the brain damage by activated microglia. So far, in an animal model of perinatal H–I, it was showed that neuroprostanes are present in all brain damaged areas, including the cerebral cortex, hippocampus and striatum. Based on the interplay between inflammation and OS, it was demonstrated in the same model that inflammation reduced brain sirtuin-1 expression and affected the expression of specific miRNAs. Moreover, through proteomic approach, an increased expression of genes and proteins in cerebral cortex synaptosomes has been revealed after induction of neonatal H–I. Administration of melatonin in the experimental treatment of brain damage and neurodegenerative diseases has produced promising therapeutic results. Melatonin protects against OS, contributes to reduce the generation of pro-inflammatory factors and promotes tissue regeneration and repair. Starting from the above cited aspects, this educational review aims to discuss the inflammatory and OS main pathways in H–I brain injury, focusing on the role of melatonin as neuroprotectant and providing current and emerging evidence.

Sex differences exist in the onset and progression of Alzheimer’s disease. Globally, women have a higher prevalence, while men with Alzheimer’s disease experience earlier mortality and more pronounced cognitive decline than women. The cause of sex differences in Alzheimer’s disease remains unclear. Accumulating evidence suggests the potential role of X-linked genetic factors in the sex difference of Alzheimer’s disease (AD). During embryogenesis, a remarkable process known as X-chromosome inactivation (XCI) occurs in females, leading to one of the X chromosomes undergoing transcriptional inactivation, which balances the effects of two X chromosomes in females. Nevertheless, certain genes exceptionally escape from XCI, which provides a basis for dual expression dosage of specific genes in females. Based on recent research findings, we explore key escape genes and their potential therapeutic use associated with Alzheimer’s disease. Also, we discuss their possible role in driving the sex differences in Alzheimer’s disease. This will provide new perspectives for precision medicine and gender-specific treatment of AD.

Multiple sclerosis (MS) is an autoimmune debilitating disease of the central nervous system caused by a mosaic of interactions between genetic predisposition and environmental factors. The pathological hallmarks of MS are chronic inflammation, demyelination, and neurodegeneration. Oxidative stress, a state of imbalance between the production of reactive species and antioxidant defense mechanisms, is considered one of the key contributors in the pathophysiology of MS. This review is a comprehensive overview of the cellular and molecular mechanisms by which oxidant species contribute to the initiation and progression of MS including mitochondrial dysfunction, disruption of various signaling pathways, and autoimmune response activation. The detrimental effects of oxidative stress on neurons, oligodendrocytes, and astrocytes, as well as the role of oxidants in promoting and perpetuating inflammation, demyelination, and axonal damage, are discussed. Finally, this review also points out the therapeutic potential of various synthetic antioxidants that must be evaluated in clinical trials in patients with MS.