Band 29, Heft 2

The trigeminal system is one of the most complex cranial nerve systems of the human body. Research on it has vastly grown in recent years and concentrated more and more on molecular mechanisms and pathophysiology, but thorough reviews on this topic are lacking, certainly on the normal physiology of the trigeminal sensory system. Here we review the current literature on neurophysiology of the trigeminal nerve from peripheral receptors up to its central projections toward the somatosensory cortex. We focus on the most recent scientific discoveries and describe historical relevant research to substantiate further. One chapter on new insights of the pathophysiology of pain at the level of the trigeminal system is added. A database search of Medline, Embase and Cochrane was conducted with the search terms ‘animal study’, ‘neurophysiology’, ‘trigeminal’, ‘oral’ and ‘sensory’. Articles were manually selected after reading the abstract and where needed the article. Reference lists also served to include relevant research articles. Fifty-six articles were included after critical appraisal. Physiological aspects on mechanoreceptors, trigeminal afferents, trigeminal ganglion and central projections are reviewed in light of reference works. Embryologic and anatomic insights are cited where needed. A brief description of pathophysiology of pain pathways in the trigeminal area and recent advances in dental stem cell research are also discussed. Neurophysiology at the level of the central nervous system is not reviewed. The current body of knowledge is mainly based on animal and cadaveric studies, but recent advancements in functional imaging and molecular neuroscience are elucidating the pathways and functioning of this mixed nerve system. Extrapolation of animal studies or functioning of peripheral nerves should be warranted.

The growth and regeneration of axons are the core processes of nervous system development and functional recovery. They are also related to certain physiological and pathological conditions. For decades, it has been the consensus that a new axon is formed by adding new material at the growth cone. However, using the existing technology, we have studied the structural tension of the nerve cell, which led us to hypothesize that some subcellular structural tensions contribute synergistically to axonal growth and regeneration. In this review, we classified the subcellular structural tension, osmotic pressure, microfilament and microtubule-dependent tension involved controllably in promoting axonal growth. A squeezing model was built to analyze the mechanical mechanism underlying axonal elongation, which may provide a new view of axonal growth and inspire further research.

Traumatic brain injury (TBI) is a contemporary health problem and a leading cause of mortality and morbidity worldwide. Survivors of TBI frequently experience disabling long-term changes in cognition, sensorimotor function, and personality. A crucial step in understanding TBI and providing better treatment has been the use of models to mimic the event under controlled conditions. Here, we describe the known head injury models, which can be classified as whole animal ( in vivo ), in vitro , and mathematical models. We will also review the ways in which these models have advanced the knowledge of TBI.

White matter injury (WMI) often results in cognitive impairment, behavioral disorders, and cerebral palsy and thus imposes a tremendous burden on society. The cells in brain white matter mainly comprise oligodendrocytes (OLs), astrocytes, and microglia. The dysregulation of OLs development is the pathological hallmark of WMI. Recent studies have demonstrated that microRNAs (miRNAs or miRs) participate in the regulation of OLs development, and the dysregulation of this process represents the pathogenesis of WMI. This review summarizes the progress made in this field that will help clinicians and researchers understand the molecular etiology of WMI and develop miRNAs as new agents for the prevention and treatment of WMI.

Pathology of Alzheimer’s disease (AD) goes far beyond neurotoxicity resulting from extracellular deposition of amyloid β (Aβ) plaques. Aberrant cleavage of amyloid precursor protein and accumulation of Aβ in the form of the plaque or neurofibrillary tangles are the known primary culprits of AD pathogenesis and target for various regulatory mechanisms. Hyper-phosphorylation of tau, a major component of neurofibrillary tangles, precipitates its aggregation and prevents its clearance. Lipid particles, apolipoproteins and lipoprotein receptors can act in favor or against Aβ and tau accumulation by altering neural membrane characteristics or dynamics of transport across the blood-brain barrier. Lipids also alter the oxidative/anti-oxidative milieu of the central nervous system (CNS). Irregular cell cycle regulation, mitochondrial stress and apoptosis, which follow both, are also implicated in AD-related neuronal loss. Dysfunction in synaptic transmission and loss of neural plasticity contribute to AD. Neuroinflammation is a final trail for many of the pathologic mechanisms while playing an active role in initiation of AD pathology. Alterations in the expression of microRNAs (miRNAs) in AD and their relevance to AD pathology have long been a focus of interest. Herein we focused on the precise pathomechanisms of AD in which miRNAs were implicated. We performed literature search through PubMed and Scopus using the search term: (‘Alzheimer Disease’) OR (‘Alzheimer’s Disease’) AND (‘microRNAs’ OR ‘miRNA’ OR ‘MiR’) to reach for relevant articles. We show how a limited number of common dysregulated pathways and abnormal mechanisms are affected by various types of miRNAs in AD brain.

Learning is essential. It allows animals to change circumstances, deal with new situations and adapt to environments. Here, we argue that learning, at behavioral and neural levels, involves efficiency, reflected in metabolic cost reductions. Behaviourally, although multiple solutions to a novel problem may be available, all solutions are not learnt – it is too costly. Furthermore, once a strategy has been selected, it is reinforced producing an efficiency that leads to a maximisation of performance and metabolic cost reductions. Learning can be represented in the brain through many mechanisms; however, if learning is truly efficient, then, all such mechanisms should also be accompanied by a reduction in measurable metabolic costs. By thinking about learning in terms of efficiency, not simply as a descriptive term but rather in terms of metabolic costs, it allows learning to be examined more carefully and provides predictions that can be easily tested (and indeed refuted).

Noninvasive brain stimulation (NIBS) modifies corticospinal excitability (CSE) historically in a predictable manner dependent on stimulation parameters. Researchers, however, discuss high degrees of variability between individuals, either responding as expected or not responding as expected. The explanation for this interindividual variability remains unknown with suggested interplay between stimulation parameters and variations in biological, anatomical, and physiological factors. This systematic review and meta-analysis aimed to investigate the effect of variation in inherent factors within an individual (biological and anatomical factors) on CSE in response to NIBS of the primary motor cortex. Twenty-two studies were included investigating genetic variation (n=7), age variation (n=4), gender variation (n=7), and anatomical variation (n=5). The results indicate that variation in brain-derived neurotrophic factor genotypes may have an effect on CSE after NIBS. Variation between younger and older adults also affects CSE after NIBS. Variation between age-matched males and females does not affect CSE after NIBS, but variation across the menstrual cycle does. Variation between skull thickness and brain tissue morphology influences the electric field magnitude that ultimately reaches the primary motor cortex. These findings indicate that biological and anatomical variations may in part account for interindividual variability in CSE in response to NIBS of the primary motor cortex, categorizing individuals as responding as expected (responders) or not responding as expected (nonresponders).

Sham stimulation is used in randomized controlled trials (RCTs) to assess the efficacy of active stimulation and placebo effects. It should mimic the characteristics of active stimulation to achieve blinding integrity. The present study was a systematic review and meta-analysis of the published literature to identify the effects of sham transcranial electrical stimulation (tES) – including anodal and cathodal transcranial direct current stimulation (a-tDCS, c-tDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS) and transcranial pulsed current stimulation (tPCS) – on corticospinal excitability (CSE), compared to baseline in healthy individuals. Electronic databases – PubMed, CINAHL, Scopus, Science Direct and MEDLINE (Ovid) – were searched for RCTs of tES from 1990 to March 2017. Thirty RCTs were identified. Using a random-effects model, meta-analysis of a-tDCS, c-tDCS, tACS, tRNS and tPCS studies showed statistically non-significant pre-post effects of sham interventions on CSE. This review found evidence for statically non-significant effects of sham tES on CSE.