The thermodynamic theory of action potential propagation: a sound basis for unification of the physics of nerve impulses

The thermodynamic theory of action potential propagation challenges the conventional understanding of the nerve signal as an exclusively electrical phenomenon. Often misunderstood as to its basic tenets and predictions, the thermodynamic theory is virtually ignored in mainstream neuroscience. Addressing a broad audience of neuroscientists, we here attempt to stimulate interest in the theory. We do this by providing a concise overview of its background, discussion of its intimate connection to Albert Einstein’s treatment of the thermodynamics of interfaces and outlining its potential contribution to the building of a physical brain theory firmly grounded in first principles and the biophysical reality of individual nerve cells. As such, the paper does not attempt to advocate the superiority of the thermodynamic theory over any other approach to model the nerve impulse, but is meant as an open invitation to the neuroscience community to experimentally test the assumptions and predictions of the theory on their validity.

Private Practitioners Knowledge of Local Anaesthetic Systemic Toxicity (LAST)

BACKGROUND Local anaesthetics (LAs) by definition are drugs that reversibly block the transmission of a nerve impulse, causing reversible absence of pain sensations without affecting consciousness. As a complication of local anaesthetic administration, a condition called as local anaesthetic systemic toxicity (LAST) can occur which affects central nervous system (CNS) and cardiovascular system (CVS). Local anaesthetic systemic toxicity is a very serious condition that can cause death. In LAST, blood levels of anaesthetic agent exceed the maximum dose, usually as a result of multiple injections or an accidental injection into a vein. The main objective of this survey was to assess the knowledge of LAST among private practitioners and to spread awareness about this common but often neglected complication of local anaesthetic administration. METHODS A survey was conducted with a questionnaire comprising of 15 questions for 251 private practitioners (registered in Indian Dental Association, Gurugram). The survey was mailed to the participants and the response was collected through online mode only. Using Excel program, the results were organized in graphs and tables, and presented as descriptive statistics. RESULTS Of the 251 surveys sent online, 151 were completed, with a survey completion rate of 60 %. On an average, only 39.9 % of the participating dentists had adequate knowledge of local anaesthetic systemic toxicity. Based on the survey, only 3.3 % of participating dentists knew how to use lipid treatment and 55.6 % had no idea about lipid treatment. CONCLUSIONS If LAST occurs, the key is to recognize it immediately and institute appropriate management. Based on the survey, there is a need to create awareness about local anaesthetic systemic toxicity and its management among dentists. KEY WORDS Local Anaesthesia, Last, Complication, Toxicity, Overdose

The Multiple Roles of Sphingomyelin in Parkinson’s Disease

Advances over the past decade have improved our understanding of the role of sphingolipid in the onset and progression of Parkinson’s disease. Much attention has been paid to ceramide derived molecules, especially glucocerebroside, and little on sphingomyelin, a critical molecule for brain physiopathology. Sphingomyelin has been proposed to be involved in PD due to its presence in the myelin sheath and for its role in nerve impulse transmission, in presynaptic plasticity, and in neurotransmitter receptor localization. The analysis of sphingomyelin-metabolizing enzymes, the development of specific inhibitors, and advanced mass spectrometry have all provided insight into the signaling mechanisms of sphingomyelin and its implications in Parkinson’s disease. This review describes in vitro and in vivo studies with often conflicting results. We focus on the synthesis and degradation enzymes of sphingomyelin, highlighting the genetic risks and the molecular alterations associated with Parkinson’s disease.

Dynamic early clusters of nodal proteins contribute to node of Ranvier assembly during myelination of peripheral neurons

Voltage-gated sodium channels cluster in macromolecular complexes at nodes of Ranvier to promote rapid nerve impulse conduction in vertebrate nerves. Node assembly in peripheral nerves is thought to be initiated at heminodes at the extremities of myelinating Schwann cells and fusion of heminodes results in the establishment of nodes. Here we show that assembly of 'early clusters' of nodal proteins in the murine axonal membrane precedes heminode formation. The Neurofascin (Nfasc) proteins are essential for node assembly, and the formation of early clusters also requires neuronal Nfasc. Early clusters are mobile and their proteins are dynamically recruited by lateral diffusion. They can undergo fusion not only with each other but also with heminodes thus contributing to the development of nodes in peripheral axons. The formation of early clusters constitutes the earliest stage in peripheral node assembly and expands the repertoire of strategies that have evolved to establish these essential structures.

The effects of mechanical noise bandwidth on balance across flat and compliant surfaces

Although the application of sub-sensory mechanical noise to the soles of the feet has been shown to enhance balance, there has been no study on how the bandwidth of the noise affects balance. Here, we report a single-blind randomized controlled study on the effects of a narrow and wide bandwidth mechanical noise on healthy young subjects’ sway during quiet standing on firm and compliant surfaces. For the firm surface, there was no improvement in balance for both bandwidths—this may be because the young subjects could already balance near-optimally or optimally on the surface by themselves. For the compliant surface, balance improved with the introduction of wide but not narrow bandwidth noise, and balance is improved for wide compared to narrow bandwidth noise. This could be explained using a simple model, which suggests that adding noise to a sub-threshold pressure stimulus results in markedly different frequency of nerve impulse transmitted to the brain for the narrow and wide bandwidth noise—the frequency is negligible for the former but significantly higher for the latter. Our results suggest that if a person’s standing balance is not optimal (for example, due to aging), it could be improved by applying a wide bandwidth noise to the feet.

On the study of seizures in newborns and early age children (features of diagnosis and clinical and genetic characteristics of epileptic encephalopathies)

The article is devoted to the urgent problem of neonatology and pediatric neurology — seizures in newborns and young children. In the work, a short review of the clinical and genetic characteristics of monogenic epilepsy is presented, in particular, the main attention is paid to the variants that begin in neonatal and early childhood. It has been shown that a significant number of epileptic encephalopathies are caused by mutations in genes whose protein products form voltage-dependent (sodium and potassium), ligan(dependent (γ-aminobutyric acid — GABA) channels, the functioning of which ensures the passage of a nerve impulse in neurons of the cerebral cortex. The necessity of including the molecular genetic methods into the algorithm for examining a child with epilepsy, in particular with epileptic encephalopathy, is emphasized. It is noted that congenital metabolic disorders are one of the etiological reasons for the development of epileptic seizures in children, in particular in newborns and young children. It was shown that congenital metabolic disorders have phenotypic manifestations of epileptic encephalopathy. Some curable metabolic defects that are accompanied by seizures, their diagnosis and timely treatment are described. No conflict of interest was declared by the authors. Key words: newborn, epilepsy, epileptic encephalopathy, diagnosis, genetic examination, metabolic defects, review.

Protracted Hiccups Induced by Aripiprazole and Regressed after Administration of Gabapentin

Hiccups are sudden, repeated, and involuntary contractions of the diaphragm muscle (myoclonic contraction). It involves a reflex arc that, once activated, causes a strong contraction of the diaphragm immediately followed by the closure of the glottis translating into the classic “hic” sound. Hiccups can be short, persistent, and intractable depending on the duration. The most disabling hiccups often represent the epiphenomenon of a medical condition such as gastrointestinal and cardiovascular disorders; central nervous system (CNS) abnormalities; ear, nose, and throat (ENT) conditions or pneumological problems; metabolic/endocrine disorders; infections; and psychogenic disorders. Some drugs, such as aripiprazole, a second-generation antipsychotic, can induce the onset of variable hiccups. We describe herein the cases of three hospitalized patients who developed insistent hiccups after taking aripiprazole and who positively responded to low doses of gabapentin. It is probable that aripiprazole, prescribed at a low dosage (<7.5 mg/day), would act as a dopamine agonist by stimulating D2 and D3 receptors at the “hiccup center” level—located in the brain stem—thus triggering the hiccup. On the other hand, gabapentin led to a complete regression of the hiccup probably by reducing the nerve impulse transmission and modulating the diaphragmatic activity. The present case series suggests the use of low doses of gabapentin as an effective treatment for aripiprazole-induced hiccups. However, our knowledge of the neurotransmitter functioning of the hiccup reflex arc is still limited, and further research is needed to characterize the neurotransmitters involved in hiccups for potential novel therapeutic targets.

Therapeutic Potential of GABAergic Signaling in Myelin Plasticity and Repair

Oligodendrocytes (OLs) produce myelin to insulate axons. This accelerates action potential propagation, allowing nerve impulse information to synchronize within complex neuronal ensembles and promoting brain connectivity. Brain plasticity includes myelination, a process that starts early after birth and continues throughout life. Myelin repair, followed by injury or disease, requires new OLs differentiated from a population derived from oligodendrocyte precursor cells (OPCs) that continue to proliferate, migrate and differentiate to preserve and remodel myelin in the adult central nervous system. OPCs represent the largest proliferative neural cell population outside the adult neurogenic niches in the brain. OPCs receive synaptic inputs from glutamatergic and GABAergic neurons throughout neurodevelopment, a unique feature among glial cells. Neuron-glia communication through GABA signaling in OPCs has been shown to play a role in myelin plasticity and repair. In this review we will focus on the molecular and functional properties of GABAA receptors (GABAARs) expressed by OPCs and their potential role in remyelination.

On Convergence Analysis and Analytical Solutions of the Conformable Fractional Fitzhugh–Nagumo Model Using the Conformable Sumudu Decomposition Method

The current article studied a nonlinear transmission of the nerve impulse model, the Fitzhugh–Nagumo (FN) model, in the conformable fractional form with an efficient analytical approach based on a combination of conformable Sumudu transform and the Adomian decomposition method. Convergence analysis and error analysis were also carried out based on the Banach fixed point theory. We also provided some examples to support our results. The results obtained revealed that the presented approach is very fantastic, effective, reliable, and is an easy method to handle specific problems in various fields of applied sciences and engineering. The Mathematica software carried out all the computations and graphics in this paper.