Progress in neurobiology
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Progress in neurobiology · Jul 2007
ReviewNeural plasticity after peripheral nerve injury and regeneration.
Injuries to the peripheral nerves result in partial or total loss of motor, sensory and autonomic functions conveyed by the lesioned nerves to the denervated segments of the body, due to the interruption of axons continuity, degeneration of nerve fibers distal to the lesion and eventual death of axotomized neurons. Injuries to the peripheral nervous system may thus result in considerable disability. After axotomy, neuronal phenotype switches from a transmitter to a regenerative state, inducing the down- and up-regulation of numerous cellular components as well as the synthesis de novo of some molecules normally not expressed in adult neurons. ⋯ Recent research has uncovered that peripheral nerve injuries induce a concurrent cascade of events, at the systemic, cellular and molecular levels, initiated by the nerve injury and progressing throughout plastic changes at the spinal cord, brainstem relay nuclei, thalamus and brain cortex. Mechanisms for these changes are ubiquitous in central substrates and include neurochemical changes, functional alterations of excitatory and inhibitory connections, atrophy and degeneration of normal substrates, sprouting of new connections, and reorganization of somatosensory and motor maps. An important direction for ongoing research is the development of therapeutic strategies that enhance axonal regeneration, promote selective target reinnervation, but are also able to modulate central nervous system reorganization, amplifying those positive adaptive changes that help to improve functional recovery but also diminishing undesirable consequences.
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Progress in neurobiology · Dec 2006
ReviewMitochondrial trafficking and morphology in healthy and injured neurons.
Mitochondria are the primary generators of ATP and are important regulators of intracellular calcium homeostasis. These organelles are dynamically transported along lengthy neuronal processes, presumably for appropriate distribution to cellular regions of high metabolic demand and elevated intracellular calcium, such as synapses. The removal of damaged mitochondria that produce harmful reactive oxygen species and promote apoptosis is also thought to be mediated by transport of mitochondria to autophagosomes. ⋯ Recent studies reveal different manifestations and mechanisms of impaired mitochondrial movement and altered morphology in injured neurons. These are likely to cause varied courses toward neuronal degeneration and death. The goal of this review is to provide an appreciation of the full range of mitochondrial function, morphology and trafficking, and the critical role these parameters play in neuronal physiology and pathophysiology.
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Norepinephrine is involved in intrinsic control of pain. Main sources of norepinephrine are sympathetic nerves peripherally and noradrenergic brainstem nuclei A1-A7 centrally. Peripheral norepinephrine has little influence on pain in healthy tissues, whereas in injured tissues it has variable effects, including aggravation of pain. ⋯ While in baseline conditions the noradrenergic system may have little effect, sustained pain induces noradrenergic feedback inhibition of pain. Noradrenergic systems may also contribute to top-down control of pain, such as induced by a change in the behavioral state. Following injury or inflammation, the central as well as peripheral noradrenergic system is subject to various plastic changes that influence its antinociceptive efficacy.
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Progress in neurobiology · Feb 2006
Biography Historical ArticleJohn Eccles' studies of spinal cord presynaptic inhibition.
Presynaptic inhibition is one of many areas of neurophysiology in which Sir John Eccles did pioneering work. Frank and Fuortes first described presynaptic inhibition in 1957. Subsequently, Eccles and his colleagues characterized the process more fully and showed its relationship to primary afferent depolarization. ⋯ Activation of GABA(A) receptors opens Cl(-) channels, and Cl(-) efflux results in depolarization. Another proposed mechanism of depolarization was an increase in extracellular concentration of K(+) following neural activity. Eccles' work on presynaptic inhibition has since been extended in a variety of ways.
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The flexion or flexor reflex (FR) recorded in the lower limbs in humans (LLFR) is a widely investigated neurophysiological tool. It is a polysynaptic and multisegmental spinal response that produces a withdrawal of the stimulated limb and resembles (having several features in common) the hind-paw FR in animals. The FR, in both animals and humans, is mediated by a complex circuitry modulated at spinal and supraspinal level. ⋯ Several studies have demonstrated that LLFR excitability may be influenced by numerous physiological conditions (menstrual cycle, stress, attention, sleep and so on) and pathological states (spinal lesions, spasticity, Wallenberg's syndrome, fibromyalgia, headaches and so on). Finally, the LLFR is modulated by several drugs and neurotransmitters. In summary, study of the LLFR in humans has proved to be an interesting functional window onto the spinal and supraspinal mechanisms of pain processing and onto the spinal neural control mechanisms operating during posture and locomotion.