A cut or crush injury to a peripheral nerve results in the degeneration of that portion of the axon isolated from the cell body. The rapid degeneration of this distal segment was for many years believed to be a process intrinsic to the nerve. It was believed that Schwann cells both phagocytosed degenerating axons and myelin sheaths and also provided growth factors to promote regeneration of the damaged axons. In recent years, it has become apparent that (...) the degenerating distal segment is invaded by monocytes from the blood. We will review the evidence that these recruited macrophages play a role in both degeneration and regeneration of peripheral nerve axons after injury and consider whether the slow degeneration and poor monocyte recruitment in the central nervous system may contribute to the poor regeneration there. (shrink)

Summary Theories of familial, racial, and national degeneration in the late nineteenth and early twentieth centuries have been explored by historians in the context of social and moral pathology. At the same time nerve degeneration was studied in the post mortem room and in the laboratory but links to the broader ideology of degeneration have not been investigated by scholars. This paper joins these domains by examining the concept of Wallerian degeneration. It argues that various (...) discourses—including those of the laboratory scientist, the clinician, and the social theorist—employed the term degeneration, and these discourses frequently overlapped demonstrating that degeneration was a ubiquitous fact of Victorian and Edwardian nature. (shrink)

In the literature investigating the long history of appeals to ‘nature’, in its multiple meanings, for rules of conduct or justification of social order, little attention has been paid to a long-standing tradition in which medical and physiological arguments merged into moral and social ones. A host of medical authors, biologists, social writers and philosophers assumed that nature spoke its moral language not only in its general economy, but also within and through the body. This is why, for instance, many (...) critics of Malthus argued that physiological self-regulating mechanisms ensured a spontaneous adaptation of fertility to the circumstances. Beliefs in a beneficent economy of nature persisted when Providence was replaced by evolution. To some, they provided reasons for hope even when others worried about ‘unfit’ members of society increasing at a quicker rate than ‘fit’ ones. The nerves gradually replaced food and blood as moral mediators between society and the body. When faith in bio-social progress was shaken by degeneration theories, and fin de siècle anxiety concerned underpopulation rather than overpopulation, not an insignificant proportion of those who emphasised the bad effects of modern civilisation resorted to ideas and arguments based on a view of the body in which physiology and morality worked together. A common language and common assumptions linked the Kulturpessimisten to their optimistic eighteenth-century colleagues, in spite of their different forecasts. The present paper traces continuities and discontinuities in the operation of a persistent set of interrelated ideas and assumptions on the coalescence of the physiological and the moral across disciplines and contexts. (shrink)

This commentary provides experimental data in support of the critical role of capsaicin-sensitive primary afferent fibers in the initiation and maintenance of pathological pain. The demonstration of capsaicin-induced, centrally-evoked cutaneous hyperalgesia, and of neuroplastic changes elicited by the degeneration of C-fiber primary afferent terminals following peripheral nerve damage, indicates a significant contribution of capsaicin-sensitive sensory ganglion neurons in the development of pathological pain conditions. [coderre & katz].

This paper focuses on the make-up of different cultures in experimental neurology, neuroanatomy, and clinical psychiatry. These cultures served as important research bases for early regenerative concepts and projects in the area of neurology and psychiatry at the beginning of the 20th century. Nevertheless, the developments in brain research and clinical neurology cannot be regarded to be isolated from broader societal developments, as the discourses on social de- and regeneration, neurasthenia, nerve-weakness and experiences of the brain-injured after WWI show. (...) Societal and cultural developments directly influenced researchers’ conceptualisation, scientific ideas, and even their experimental and clinical orientation. They directly reflect which scientific problems the neuroscientists felt inclined to address and what areas they began to leave aside. Using the concept of socio-technical experiments, it is demonstrated that research methodologies in neuronal de- and regeneration studies were not simply a product of recent advances in the scientific differentiation of somatic neurology or brain-psychiatry. Moreover, they resulted in important interdisciplinary attempts which emerged from great collaborative work including neuroscientists from various areas of investigation in both basic and clinical contexts. (shrink)

Both blood vessels and nerves are guided to their target. Vascular endothelial growth factor (VEGF)A is a key signal in the induction of vessel growth (a process termed angiogenesis). Though initial studies, now a decade ago, indicated that VEGF is an endothelial cell‐specific factor, more recent findings revealed that VEGF also has direct effects on neural cells. Genetic studies showed that mice with reduced VEGF levels develop adult‐onset motor neuron degeneration, reminiscent of the human neurodegenerative disorder amyotrophic lateral sclerosis (...) (ALS). Additional genetic studies confirmed that VEGF is a modifier of motor neuron degeneration in humans and in SOD1G93A mice—a model of ALS. Reduced VEGF levels may promote motor neuron degeneration by limiting neural tissue perfusion and VEGF‐dependent neuroprotection. VEGF also affects neuron death after acute spinal cord or cerebral ischemia, and has also been implicated in other neurological disorders such as diabetic and ischemic neuropathy, nerve regeneration, Parkinson's disease, Alzheimer's disease and multiple sclerosis. These findings have raised growing interest in assessing the therapeutic potential of VEGF for neurodegenerative disorders. BioEssays 26:943–954, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The Motoneurone and its Muscle Fibres presents a state-of-the-art summary of knowledge concerning the motoneurones, vital for innervating and commanding skeletal muscles. No muscle action would be possible without motoneurones. These cells are therefore absolutely essential for the execution of normal behaviour and for life support. It is their degeneration that leads to various kinds of motoneurone disease that are often ultimately lethal. However, the study of motoneurones is also important for general insights as to how neurones work, because (...) the motoneurone is probably the best understood kind of nerve cell so far in neuroscience. Motoneurones of the spinal cord were the first type of central nerve cell to be subjected to detailed physiological measurements, and much is known about how their activity is regulated by synapses from other central neurones. For most of the individual neurones within the central nervous system, the precise functional tasks are difficult to define. However, for motoneurones much is now known about their short- and long-term interactions with their main targets, the skeletal muscle fibres. Functions of neurones must be analyzed in relation to the response properties of their target cells. Therefore, this book deals with both, summarizing classical as well as recent knowledge concerning the motoneurone and its muscle fibres. This is the first time that so many aspects of this broad subject matter are treated in one comprehensive monograph. (shrink)

Difficulty is a severe instructor, set over us by the supreme ordinance of a parental guardian and legislator, who knows us better than we know ourselves, as he loves us better too.... Our antagonist is our helper. This amicable conflict with difficulty obliges us to an intimate acquaintance with our object, and compels us to consider it in all its relations. It will not suffer us to be superficial. It is the want of nerves of understanding for such a talk; (...) it is the degenerate fondness for tricking short-cuts and little fallacious facilities, that has in so many parts of the world created governments with arbitrary powers. (Edmund Burke). (shrink)

The Liver kinase B1 with its downstream target AMP activated protein kinase (LKB1‐AMPK), and the key nutrient sensor mammalian target of rapamycin complex 1 (mTORC1) form two signaling systems that coordinate metabolic and cellular activity with changes in the environment in order to preserve homeostasis. For example, nutritional fluctuations rapidly feed back on these signaling systems and thereby affect cell‐specific functions. Recent studies have started to reveal important roles of these strategic metabolic regulators in Schwann cells for the trophic support (...) and myelination of axons. Because aberrant intermediate metabolism along with mitochondrial dysfunction in Schwann cells is mechanistically linked to nerve abnormalities found in acquired and inherited peripheral neuropathies, manipulation of the LKB1‐AMPK, and mTORC1 signaling hubs may be a worthwhile therapeutic target to mitigate nerve damage in disease. Here, recent advances in our understanding of LKB1‐AMPK and mTORC1 functions in Schwann cells are covered, and future research areas for this key metabolic signaling network are proposed. (shrink)

Epidemics of organophosphate‐induced delayed neuropathy (OPIDN) have paralysed thousands of people. This syndrome of nerve axon degeneration is initiated by organophosphates which react with neuropathy target esterase (NTE). Dosing experiments with adult chickens raise the possibility that OPIDN is initiated by a gain‐of‐function mechanism. By contrast, loss of NTE function by mutation causes massive apoptosis in Drosophila brain. Now, Winrow et al. show that nte−/− mice die by mid‐gestation, but nte+/− mice appear hyperactive and are more sensitive than (...) wild‐type mice to a fatal form of OP toxicity.1 Thus, different toxic syndromes may be initiated via a single target protein. BioEssays 25:742–745, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Stein & Glasier suggest embryonic neural tissue grafts as a potential treatment strategy for Alzheimer's and Parkinson's disease. As an alternative, we suggest that the family of nerve growth factor-related neurotrophins and their trk (tyrosine kinase) receptors underlie cholinergic basal forebrain (CBF) and dopaminergic substantia nigra neuron degeneration in these diseases, respectively. Therefore, treatment approaches for these disorders could utilize neurotrophins.

Alzheimer's disease results from the degeneration of neurons. Degenerating nerve cells express atypical proteins, and amyloid is deposited. We suggest that some of these events are strongly influenced by genetic factors and age. Animal models should be useful in investigating the pathogenic mechanisms that lead to the brain abnormalities seen in this disease.

The Classical Theory of function in the nervous system postulates that the nerve impulse is the result of a sequential reversal of the membrane potential due to an increased permeability of the membrane, first to sodium ions, then to potassium ions. The new theory presents a bio-physical model which depicts the nerve impulse as an event involving the motions of electrons and waves, and their interactions with sodium and potassium atoms and ions. The velocity of the nerve (...) impulse (the most important parameter of nerve function) is determined by the product of two constants: c = the speed of light, which is a constant for all nerves; k =a constant for each nerve and is believed to be a specific property of nerve matter related in some way to the atomic process. The theory proposes that the nerve impulse in the axon is dualistic in nature (particles and waves play equally significant roles). The dualistic nature accounts for the three most fundamental characteristics of conduction of the nerve impulse: periodicity (conduction of a nerve impulse over long distances with constant velocity and form); non-summing (two nerve impulses cannot be in the same place at the same time); quantum nature of each nerve impulse — i.e., the unit message of the nerve impulse is an indivisible unit. (shrink)

In 2001, I experienced severe radial neuropathy, leading to permanent dysfunctions in the fingers of my left hand. In this personal account of nerve damage, medical and surgical treatment, and adaptation, I first describe the sequence of neuropathies, then turn to how through serendipity, the brace enabled other connections—nervelines—with individuals and places. The brace is a metonym of a severed nerve with its associated loss of movement and capacity; it is also both a functional orthotic and an affordance. (...) It carries me forward, activating other nervelines and networks to make things happen. I write of literal and metaphoric nerves, evolving connectivities, and fiber lines, thought lines and collaborations. I then extend the idea of nervelines and networks to global connnections; I emphasize how the organization of labor, the distribution of goods and services, and the expectations of workers shape body histories and life outcomes. (shrink)

This article is about the beginnings of tissue culture-the culture of living, reproducing cells of complex organisms outside the body. It argues that Ross Harrison's experiments in nerve culture between 1907 and 1910 should be viewed as part of a larger shift in early twentieth-century laboratory practice from in vivo to in vitro experimentation. Via a focus on the temporality of experiment-contrasting the live object of Harrison's investigation with the static object of histological representations-this article details the production of (...) a new and surprising form of life, cellular life in vitro. Tissue culture, developed from Harrison's experiments, was greeted with great surprise and disbelief, despite Harrison's protestations that he had merely juxtaposed extant techniques. An analysis of these initial reactions to tissue culture illuminates the extent to which cells living visibly outside of the body in glass broke with in vivo practices and assumptions of the hiddenness and interiority of certain processes of growth and change. (shrink)

Mind and matter.--Moral nerve.--Herbert Spencer as a moralist.--Huxley as a moralist.--Substitutional morals: the principle of punishment.--Literary and scientific verdicts.--The genesis of modern kindliness.--Stuart Mill.--Thomas Carlyle.--The French revolution.--Epoch-making incidents and persons.--The slow change in the fundamental characteristics of peoples and individuals.--Emerson on Napoleon.--Goldwin Smith.--Material prosperity and religion.--Nerve forces as totalities.--The evolution of the direct man (direct brain).

Since Popper and Lakatos, the demarcation line between science and non-science has been considered one of the fundamental issues of the philosophy of science. According to Lakatos, pseudoscience is a non-science, which appears as science, using science's public authority. Since then, mountains of texts have been published on how non-sciences, such as astrology, are not sciences. -/- But the enemy is not on the other side of the border. The enemy is in our midst. Science has been institutionalized. The best (...) way to do the pseudoscience is to fuss inside the big enterprise recognized as a science. (shrink)

:Advocates of cosmopolitan ideals, to the extent that they engage with questions of institutional design, typically imagine replicating or refining existing, nation-state models of governance but on an international scale. This essay argues that cosmopolitan ethics need not go hand in hand with international government, and may be better served by a different approach. I explore the concept of degeneracy as a principle of institutional evaluation and design in international politics. Degeneracy is a characteristic of complex systems in which multiple (...) components of the system offer overlapping functions, and is a key component in the robustness of such systems. Non-degenerate systems, by contrast, exhibit fragility in the face of adverse conditions. When applied to systems of governance, degeneracy commends polycentricity and allows for some evaluation of the robustness of different mechanisms and forms of polycentric governance. Cosmopolitan ideals are better served by providing alternatives to existing forms of governance than by building on them. I consider some concrete policy applications of this idea, focusing on immigration and intellectual property. (shrink)

The chapter discusses the following quotation from Charles Peirce: "One of these days, perhaps, there will come a writer of opinions less humdrum than those of Dr. (Alfred Russel) Wallace, and less in awe of the learned and official world...who will argue, like a new Bernard Mandeville, that man is but a degenerate monkey, with a paranoic talent for self-satisfaction, no matter what scrapes he may get himself into, calling them 'civilization,' and who, in place of the unerring instincts of (...) other races, has an unhappy faculty for occupying himself with words and abstractions, and for going wrong in a hundred ways before he is driven, willy-nilly, into the right one. Dr. Wallace would condemn such an extravagant paradoxer." Charles Peirce, 1901 -/- . (shrink)

Cognitive dysfunction in Alzheimer’s disease is caused by disturbances in neuronal circuits of the brain underpinned by synapse loss, neuronal dysfunction and neuronal death. Amyloid beta and tau protein cause these pathological changes and enhance neuroinflammation, which in turn modifies disease progression and severity. Vagal nerve stimulation, via activation of the locus coeruleus, results in the release of catecholamines in the hippocampus and neocortex, which can enhance synaptic plasticity and reduce inflammatory signalling. Vagal nerve stimulation has shown promise (...) to enhance cognitive ability in animal models. Research in rodents has shown that VNS can have positive effects on basal synaptic function and synaptic plasticity, tune inflammatory signalling, and limit the accumulation of amyloid plaques. Research in humans with invasive and non-invasive VNS devices has shown promise for the modulation of cognition. However, the direct stimulation of the vagus nerve afforded with the invasive procedure carries surgical risks. In contrast, non-invasive VNS has the potential to be a broadly available therapy to manage cognitive symptoms in early AD, however, the magnitude and specificity of its effects remains to be elucidated, and the non-inferiority of the effects of non-invasive VNS as compared with invasive VNS still needs to be established. Ongoing clinical trials with healthy individuals and patients with early AD will provide valuable information to clarify the potential benefits of non-invasive VNS in cognition and AD. Whether invasive or non-invasive VNS can produce a significant improvement on memory function and whether its effects can modify the progression of AD will require further investigation. (shrink)

The essay concerns the negative end of the political argument of the Republic, that injustice—the rule of unreason—is both widespread and undesirable, and that whatever shadows of virtue or order might be found in its midst are corrupt and unstable. This claim is explained in detail in Republic 8 and 9. These passages explain recognizable faults in recognizable regimes in terms of the failure of the rule of reason and the corresponding success of the rule of non-rational forms of motivation. (...) I will first look at degenerate regimes as they appear in a less systematic way in the Ship of State passage in Republic 6 and in the discussion with Thrasymachus in book 1. I then give a general overview of the system of degenerate regimes in book 8 to examine what exactly goes wrong with them and why, and explain how the process of degeneration ought be understood as the progressive decay of the rule of reason. Finally, I argue that a close look at this decay reveals something surprising: that degenerate regimes and characters feature weak versions of virtue, shadow-virtues that are based on appearances and held in place by force. Thus in the end the whole process of degeneration ought be understood as an extended conflict between reason and appetite. (shrink)

In Philip J. Ivanhoe’s introduction to his Readings from the Lu-Wang School of Neo-Confucianism, he argues convincingly that the Ming-era Neo-Confucian philosopher Wang Yang-ming (1472–1529) was much more influenced by Buddhism (especially Zen’s Platform Sutra) than has generally been recognized. In light of this influence, and the centrality of questions of selfhood in Buddhism, in this article I will explore the theme of selfhood in Wang’s Neo-Confucianism. Put as a mantra, for Wang “self-awareness is world-awareness.” My central image for this (...) mantra is the entire cosmos anthropomorphized as a doctor engaged in constant self-diagnosis, in which effort s/he is assisted by an entire staff of the nerves/nurses—individual humans enlightened as Wangian sages. In short, I will argue that the world for Wang could be meaningfully understood as a mindful, self-healing body within which humans are the sensitive nerves, using our mindful awareness to direct attention to the affected areas when injury or disease occurs. We are, and must thus recognize that we are, the bold but sensitive nervous system of the cosmos, sharing (like neurons) our loving excitement, carrying out (like a medical nurse) the doctor’s orders for the self-care of our cosmic body/medical corps. (shrink)

Thomas Hobbes’ theory of punishment plays a constitutive role in the Leviathan’s theory of state sovereignty. Despite this, Hobbes’ justification for punishment is widely found to be discrepant, weak, inconsistent, and contradictory. Two dominant tendencies in the scholarship attempt to stabilize the Leviathan’s justification for the state’s right to punish by either identifying it with the sovereign’s right to war or by elaborating a theory of authorization within the state. In contrast, by tracing the deployments of the metaphor that Hobbes (...) utilizes to evoke the state’s right to punish in the Leviathan (i.e. that of the nerves of the Leviathan) this paper finds that these two accounts can be made to be consistent with each other — thereby destabilizing the grounds upon which the theory of punishment can be founded. (shrink)

A striking feature of John Dewey’s philosophical attitude in his later period is that for self-description, he did not prefer the term “pragmatism.” Instead, he employed such isms as “experimentalism” and “naturalism.” In the period in which he moved towards developing his own original philosophy, he even stated that “I reject root and branch to the term ‘pragmatism.’”1 As he was at the time drawn to naturalism, it might be revealing indeed that he rejects “root and branch” to “pragmatism.” Also (...) in the newly released notes for his lectures on social philosophy in China 1919, the word “pragmatism” goes without a single mention.2 The reader does not encounter the creed for a “pragmatist social... (shrink)

Background: Primary open-angle glaucoma patients exhibit widespread white matter degeneration throughout their visual pathways. Whether this degeneration starts at the pre- or post-geniculate pathways remains unclear. In this longitudinal study, we assess the progression of WM degeneration exhibited by the pre-geniculate optic tracts and the post-geniculate optic radiations of POAG patients over time, aiming to determine the source and pattern of spread of this degeneration.Methods: Diffusion-weighted MRI scans were acquired for 12 POAG patients and 14 controls (...) at two time-points 5.4 ± 2.1 years apart. Fiber density, an estimate of WM axonal density, was computed for the OTs and ORs of all participants in an unbiased longitudinal population template space. First, FD was compared between POAG patients and the controls at time-point 1 and time-point 2 independently. Secondly, repeated measures analysis was performed for FD change in POAG patients between the two time-points. Finally, we compared the rate of FD change over time between the two groups.Results: Compared to the controls, POAG patients exhibited significantly lower FD in the left OT at TP1 and in both OTs and the left OR at TP2. POAG patients showed a significant loss of FD between the time-points in the right OT and both ORs, while the left OR showed a significantly higher rate of FD loss in POAG patients compared to the controls.Conclusions: We find longitudinal progression of neurodegenerative WM changes in both the pre- and post-geniculate visual pathways of POAG patients. The pattern of changes suggests that glaucomatous WM degeneration starts at the pre-geniculate pathways and then spreads to the post-geniculate pathways. Furthermore, we find evidence that the trans-synaptic spread of glaucomatous degeneration to the post-geniculate pathways is a prolonged process which continues in the absence of detectable pre-geniculate degenerative progression. This suggests the presence of a time window for salvaging intact post-geniculate pathways, which could prove to be a viable therapeutic target in the future. (shrink)

[Accepted for publication in Lakatos's Undone Work: The Practical Turn and the Division of Philosophy of Mathematics and Philosophy of Science, special issue of Kriterion: Journal of Philosophy. Edited by S. Nagler, H. Pilin, and D. Sarikaya.] Lakatos’s analysis of progress and degeneration in the Methodology of Scientific Research Programmes is well-known. Less known, however, are his thoughts on degeneration in Proofs and Refutations. I propose and motivate two new criteria for degeneration based on the discussion in (...) Proofs and Refutations – superfluity and authoritarianism. I show how these criteria augment the account in Methodology of Scientific Research Programmes, providing a generalized Lakatosian account of progress and degeneration. I then apply this generalized account to a key transition point in the history of entropy – the transition to an information-theoretic interpretation of entropy – by assessing Jaynes’s 1957 paper on information theory and statistical mechanics. (shrink)

We present a case study of two scientific perspectives on the phenomenon of nerve signal propagation, a bio-electric and a thermodynamic perspective, and compare this case with two accounts of scientific perspectivism: those of Michela Massimi and Juha Saatsi, respectively. We demonstrate that the interaction between the bio-electric perspective and the thermodynamic perspective can be captured in Saatsi’s terms of progress in explanatory understanding. Using insights from our case study, we argue that both the epistemic and pragmatic dimensions of (...) scientific understanding are important for increasing explanatory understanding of phenomena. The epistemic dimension of understanding is important for increasing the number of actually answered what-if-things-had-been-different questions about a phenomenon, the pragmatic dimension for pointing out the potentially answerable what-if questions that have been overlooked or purposefully neglected thus far. Exposing the limitations of the acquired understanding within a particular perspective can be achieved by criticizing the assumptions that have been adopted to make models of the perspective intelligible, but that are considered problematic from a rival perspective. (shrink)

The Hungarian-born philosopher of science Imre Lakatos introduces the methodology of scientific research programs, and also makes a famous distinction between “progressive” and “degenerating” programs. Although Lakatos does not give extensive guidance as to whether philosophical rather than scientific theories could also be judged in this way, he does give some intriguing hints in his discussion of a debate on induction between Rudolf Carnap and Karl Popper. After considering two extant but misguided attempts to use “degenerating” as a polemical term (...) in philosophy, this article gathers the aforementioned hints from Lakatos and a few others from Alfred North Whitehead in an effort to identify what a “progressive philosophy” might look like. (shrink)

This article explores two very different forms in which immoral conduct was problematized over the course of the 19th century. It does this by contrasting the sexual purity politics of the Vice Society and the medicalization of morality as `moral insanity'. Early in the century the Vice Society promoted coercive legislation with the aim of `suppressing vice'. From mid-century, moral insanity theories sought to grapple with vice by disaggregating `moral' from other forms of insanity. These two movements had quite distinct (...) and incompatible lines of development; and they never overtly engaged with each other. The article makes its key argument by demonstrating the way in which such dissimilar trajectories came together towards the end of the century in the `moral hygiene' movement, mobilizing discourses of `degeneration' (and `feeblemindedness') with projects promoting sexual purity. (shrink)

The type of cognitive theory of emotion traditionally espoused by philosophers of mind makes two central claims. First, that the occurrence of propositional attitudes is essential to the occurrence of emotions. Second, that the identity of a particular emotional state depends upon the propositional attitudes that it involves. In this paper I try to show that there is little hope of developing a theory of emotion which makes these claims true. I examine the underlying defects of the programme, and show (...) that several recent variants fail to repair these defects. Furthermore, even if such a theory could be developed, it would not achieve many of the things that we look to a theory of emotion for. I argue that philosophers should turn their attention to new and more promising approaches. These have been developed by various of the special sciences, while philosophy has remained enthralled by traditional, propositional attitude psychology. (shrink)