Volume 26, Issue 2

Transplantation of Schwann cells (SCs) is a promising therapeutic strategy for spinal cord repair. The introduction of SCs into the injured spinal cord has been shown to reduce tissue loss, promote axonal regeneration, and facilitate myelination of axons for improved sensorimotor function. The pathology of spinal cord injury (SCI) comprises multiple processes characterized by extensive cell death, development of a milieu inhibitory to growth, and glial scar formation, which together limits axonal regeneration. Many studies have suggested that significant functional recovery following SCI will not be possible with a single therapeutic strategy. The use of additional approaches with SC transplantation may be needed for successful axonal regeneration and sufficient functional recovery after SCI. An example of such a combination strategy with SC transplantation has been the complementary administration of neuroprotective agents/growth factors, which improves the effect of SCs after SCI. Suspension of SCs in bioactive matrices can also enhance transplanted SC survival and increase their capacity for supporting axonal regeneration in the injured spinal cord. Inhibition of glial scar formation produces a more permissive interface between the SC transplant and host spinal cord for axonal growth. Co-transplantation of SCs and other types of cells such as olfactory ensheathing cells, bone marrow mesenchymal stromal cells, and neural stem cells can be a more effective therapy than transplantation of SCs alone following SCI. This article reviews some of the evidence supporting the combination of SC transplantation with additional strategies for SCI repair and presents a prospectus for achieving better outcomes for persons with SCI.

Hydrogen sulfide (H 2 S) is an endogenously produced gas that represents a novel third gaseous signaling molecule, neurotransmitter and cytoprotectant. Cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), 3-mercaptopyruvate sulfur transferase with cysteine aminotransferase (3-MST/CAT) and 3-mercaptopyruvate sulfur transferase with d -amino acid oxidase (3-MST/DAO) pathways are involved in the generation of endogenous H 2 S despite the ubiquitous or restricted distribution of those enzymes. CBS, 3-MST/CAT and 3-MST/DAO can be found in the brain, while CSE is widely located in other organs. There also exist up-taking or recycling and scavenging mechanisms in H 2 S metabolism to maintain its persistence for physiological function. In recent years, investigating the role that H 2 S plays in the central nervous system and cardiovascular system has always been a hotspot. To date, effects of H 2 S are at least partially verified in multiple animal models or neuron cell lines of Alzheimer’s disease, Parkinson’s disease, cerebral ischemia, major depression disorders and febrile seizure, although subsequent studies are still badly needed. This article presents an overview of current knowledge of H 2 S focusing on its neuroprotective effects and corresponding signaling pathways, together with connections to potential therapeutic strategies in the clinic.

Neuroinflammation is as an important component of pathogenesis in many types of brain pathology. Immune mechanisms regulate neuroplasticity, memory formation, neurogenesis, behavior, brain development, cognitive functions, and brain metabolism. It is generally believed that essential homeostatic functions of astrocytes – astroglia-neuron metabolic coupling, gliovascular control, regulation of proliferation, and migration of cells in the neurogenic niches – are compromised in neuroinflammation resulting in excitotoxicity, neuronal and glial cell death, and alterations of intercellular communication. Viral neuroinfection, release of non-coding RNAs from the cells at the sites of brain injury or degeneration, and application of siRNA or RNA aptamers as therapeutic agents would require dsRNA-sensing pathways in the cells of neuronal and non-neuronal origin. In this review, we analyze the data regarding the role of astrocytes in dsRNA-initiated innate immune response in neuroinflammation and their contribution to progression of neurodegenerative and neurodevelopmental pathology.

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease that rapidly progresses from mild motor symptoms to severe motor paralysis and premature death. There is currently no cure for this devastating disease; most ALS patients die of respiratory failure generally within 3–5 years from the onset of signs and symptoms. Approximately 90% of ALS cases are sporadic in nature, with no clear associated risk factors. It is reported that ALS is a complex and multifaceted neurodegenerative disease. Less is known about the key factors involved in the sporadic form of the disease. The intricate pathogenic mechanisms that target motor neurons in ALS includes oxidative stress, glutamate excitotoxicity, mitochondrial damage, protein aggregation, glia and neuroinflammation pathology, defective axonal transport, and aberrant RNA metabolism. Despite aggressive research, no therapy has been yet proven to completely reverse the core symptoms of the disease. Riluzole is the only drug approved by the Food and Drug Administration and recommended by the National Institute for Clinical Excellence so far proven to be successful against ALS and may prevent progression and extend life for a few months or so. This article provides a novel understanding in key findings of pathogenesis and interventions currently under investigation to slow disease progression in ALS.

Spreading depression (SD) is a wave phenomenon in gray matter tissue. Locally, it is characterized by massive redistribution of ions across cell membranes. As a consequence, there is sustained membrane depolarization and tissue polarization that depress any normal electrical activity. Despite these dramatic events, SD remains difficult to observe in humans noninvasively, which, for long, has slowed advances in this field. The growing appreciation of its clinical importance in migraine and stroke is therefore consistent with an increasing need for computational methods that tackle the complexity of the problem at multiple levels. In this review, we focus on mathematical tools to investigate the question of spread and its two complementary aspects: What are the physiological mechanisms and what is the spatial extent of SD in the cortex? This review discusses two types of models used to study these two questions, namely, Hodgkin-Huxley type and generic activator-inhibitor models, and the recent advances in techniques to link them.

Accumulating evidence suggests that neuronal nicotinic acetylcholine receptors (nAChRs) may play a key role in the pathophysiology of some neurological diseases such as epilepsy. Based on genetic studies in patients with epileptic disorders worldwide and animal models of seizure, it has been demonstrated that nAChR activity is altered in some specific types of epilepsy, including autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and juvenile myoclonic epilepsy (JME). Neuronal nAChR antagonists also have antiepileptic effects in pre-clinical studies. There is some evidence that conventional antiepileptic drugs may affect neuronal nAChR function. In this review, we re-examine the evidence for the involvement of nAChRs in the pathophysiology of some epileptic disorders, especially ADNFLE and JME, and provide an overview of nAChR antagonists that have been evaluated in animal models of seizure.

Epilepsy is a serious chronic neurologic disorder characterized by recurrent unprovoked seizures resulting from abnormal and highly synchronous neuronal discharges within the brain. Small noncoding RNAs, called microRNAs, play vital roles in epileptogenesis, with potential contributions as valuable biomarkers and targets for the treatment of epilepsy. To maintain cellular homeostasis, cellular components, such as organelles, proteins, protein complexes/oligomers, and pathogens, are delivered to the lysosome for degradation through a process called autophagy, which plays either a protective or a harmful role under epileptic stress. Several autophagic mechanisms have been implicated in epileptogenesis, including the mammalian target of rapamycin pathway, aberrant substrate accumulation, and the formation of epileptic networks. In addition, the regulation of autophagy through microRNAs (miRNAs) represents a novel posttranscriptional regulatory mechanism through ‘autophagamiRNAs’. The correlation between autophagy and miRNA has increased our understanding of the underlying pathogenesis of human diseases. Here, we review the current findings regarding the correlations between miRNA, autophagy, and epilepsy to provide a solid foundation for further examination of the miRNA-autophagy pathway involved in epilepsy pathophysiology.

Peripheral nerve hyperexcitability (PNH) syndromes can be subclassified as primary and secondary. The main primary PNH syndromes are neuromyotonia, cramp-fasciculation syndrome (CFS), and Morvan’s syndrome, which cause widespread symptoms and signs without the association of an evident peripheral nerve disease. Their major symptoms are muscle twitching and stiffness, which differ only in severity between neuromyotonia and CFS. Cramps, pseudomyotonia, hyperhidrosis, and some other autonomic abnormalities, as well as mild positive sensory phenomena, can be seen in several patients. Symptoms reflecting the involvement of the central nervous system occur in Morvan’s syndrome. Secondary PNH syndromes are generally seen in patients with focal or diffuse diseases affecting the peripheral nervous system. The PNH-related symptoms and signs are generally found incidentally during clinical or electrodiagnostic examinations. The electrophysiological findings that are very useful in the diagnosis of PNH are myokymic and neuromyotonic discharges in needle electromyography along with some additional indicators of increased nerve fiber excitability. Based on clinicopathological and etiological associations, PNH syndromes can also be classified as immune mediated, genetic, and those caused by other miscellaneous factors. There has been an increasing awareness on the role of voltage-gated potassium channel complex autoimmunity in primary PNH pathogenesis. Then again, a long list of toxic compounds and genetic factors has also been implicated in development of PNH. The management of primary PNH syndromes comprises symptomatic treatment with anticonvulsant drugs, immune modulation if necessary, and treatment of possible associated dysimmune and/or malignant conditions.