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Biomedical subjects

E Yoles

Publications and source records attributed to E Yoles.

46 records · Page 3Linked to original sources
PubMed1994

Inflammation after axonal injury has conflicting consequences for recovery of function: rescue of spared axons is impaired but regeneration is supported.

Neural injury leads to tissue damage beyond that caused by the initial lesion, mainly as a result of a chain of autodestructive events triggered by the trauma. These events apparently include the activation of immune-derived cells and their products, as treatment with anti-inflammatory agents, such as corticosteroids, limits the damage and thus improves recovery. On the other hand, immune-derived substances, such as cytokines, are thought to play an important role in post-traumatic axonal regeneration. Thus, the need to reduce inflammation to limit the spread of damage appears to be in conflict with the need to permit inflammation to promote regeneration. Comprehension and resolution of this apparent conflict may lead to the development of treatment protocols aimed at rescuing axons spared by the initial injury, without hampering the potential regeneration of directly and indirectly injured axons. In this study, carried out on rats with crushed optic nerves, daily intraperitoneal injections of dexamethasone commencing prior to the injury significantly attenuated the injury-induced decrease in electrophysiological activity and reduced the area of tissue damage. On the other hand, dexamethasone treatment reduced the permissiveness of the injured nerves to neural adhesion and regrowth in vitro. This latter phenomenon was also observed in injured peripheral nerves. Results are discussed with respect to the possible establishment of an appropriate protocol for corticosteroid treatment of nerve injuries aimed at promoting neuronal rescue without compromising neuronal regeneration.

Adrenal Cortex Hormones↗
PubMed1993

Gangliosides attenuate axonal loss after optic nerve injury.

Gangliosides have been shown to be capable of protecting nerve tissue from mechanical and biochemical insults and promoting their repair. The present study provides morphologic evidence that monosialogangliosides attenuate the degenerative process at the distal stump of the rat optic nerve after crush injury. Injured rat optic nerves were treated for 7 days after injury with daily intraperitoneal injections of monosialogangliosides (30 mg/kg/day), and compared with untreated injured controls with respect to the number of viable axons 2 and 4 weeks after injury, as indicated by transmission electron microscopy. After 2 weeks, the mean number of viable axons in the treated optic nerves (n = 5) was slightly higher than in the controls (n = 5). Four weeks after injury, although the absolute number in both the experimental and the control groups had dropped, it was about seven-fold higher in the treated animals (1696 +/- 1149, n = 7) than in the untreated animals (216 +/- 65, n = 6); this difference was statistically significant. These findings, which offer some insight as to how monosialogangliosides affect injured nerves, may have important implications for treatment in cases of optic nerve injury.

Animals↗
PubMed1992

GM1 reduces injury-induced metabolic deficits and degeneration in the rat optic nerve.

This study demonstrates the earliest reported effects of GM1 treatment on crush-injured axons of the mammalian optic nerve. GM1, administered intraperitoneally immediately after injury, was found to reduce the injury-induced metabolic deficit in nerve activity within 2 hr of injury, as measured by changes in the nicotine-amine adenine dinucleotide redox state. After 4 wk, transmission electron microscopy 1 mm distal to the site of injury revealed a sevenfold increase in axonal survival in GM1-treated compared to untreated injured nerves. These results emphasize the beneficial effect of GM1 on injured optic nerves as well as the correlation between immediate and long-term consequences of the injury. Thus, these results have implications for treating damaged optic nerves.

Animals↗
PubMed1990

Brain mitochondrial redox state, tissue haemodynamic and extracellular ion responses to four-vessel occlusion and spreading depression in the rat.

Fibre-optic surface fluorometer reflectrometry was used to monitor the NADH (nicotine adenine dinucleotide) redox state from rat brain during three- or four-vessel occlusion. To compare the completeness of the electrocauterization of the vertebral arteries and the effectiveness of the anterior cerebral arteries, two light guides were implanted above the cerebral hemispheres. The NADH level was measured and correlated with the changes in the intensity of the reflected light at the excitation wavelength (366 nm) and to the ECoG (electrocorticogram). In the present study, we used ten rats in which unilateral and bilateral carotid occlusion were performed. In a second group of rats we tested the effects of four-vessel occlusion on the metabolic and extracellular K+ and Ca2+ activities as compared with those recorded under spreading depression conditions. These experiments were done by using the multiprobe assembly (MPA) approach. The results could be summarized as follows: (1) in the four-vessel occlusion model, the level of cerebral ischaemia could be estimated quantitatively, in real-time, by monitoring the NADH redox state; (2) unilateral carotid occlusion (after vertebral coagulation) led to a variable level of ipsilateral ischaemia, depending upon the blood flow compensation between the two hemispheres; (3) fibre-optic fluorometry enabled the correlation of NADH redox state with other physiological parameters as well as during after-brain ischaemia; (4) using the MPA in rats exposed to four-vessel occlusion as well as spreading depression, we identified the differences between the two pathological states, although there were some similarities in the ion homeostasis responses.

Animals↗
PubMed1983

Evidence for a functional role of acetylcholinesterase in cultured chick myotubes.

This study was undertaken in order to assess the functional role of acetylcholinesterase (AChE) in cultures of chick skeletal muscle cells. Cultures of skeletal myotubes were prepared by mechanical dissociation of limb muscle removed from 11-day-old chick embryos and plating at a concentration of 0.8 X 10(6) cells/ml. Cultures incubated for 4-10 days were used for electrophysiological studies with intracellular microelectrodes. Individual myotubes differed with respect to the time course of repolarization following depolarization by acetylcholine (ACh), some cells repolarizing within 2-3 min and others only after 8-10 min. Physostigmine (10(-8)-10(-6) M) prolonged or sometimes completely prevented repolarization following ACh-induced depolarization. These results demonstrate that hydrolysis of ACh by AChE in cultured chick skeletal myotubes plays an important role in the repolarization of these cells following ACh-induced depolarization.

Acetylcholine↗
PubMedDate not supplied

Potential neuroprotective therapy for glaucomatous optic neuropathy.

Accumulating evidence points to the existence of a mechanism that may explain why glaucomatous neuropathy continues to progress even after its primary cause, e.g., high intraocular pressure, has been alleviated or attenuated. We suggest that such a mechanism involves processes collectively termed secondary degeneration, an inevitable outcome of acute injury of the central nervous system. Secondary degeneration refers to the spread of degeneration to apparently healthy neurons that escaped the primary insult, but are adjacent to the injured neurons and are thus exposed to the degenerative milieu that the latter create. Neuroprotection, i.e., protection of undamaged neurons from secondary degeneration, would therefore require that the extracellular elements associated with the degeneration be neutralized, balanced off, or inhibited. In seeking an experimental framework for testing treatment modalities for neuroprotection, we have developed an animal model in which a well-calibrated, reproducible, partial lesion is inflicted on the optic nerve of the adult rat. Using this model, the extent of the primary damage can be quantified and the secondary degeneration demonstrated and assessed. Damage inflicted directly on the optic nerve fibers inevitably leads to their degeneration and the eventual death of their cell bodies. Over time, neurons that initially escaped the injury undergo self-perpetuating secondary degeneration, the extent of which is a function of the severity of the primary insult. We suggest that a similar mechanism may underlie the propagation of damage seen in glaucoma at any given time after alleviation of the primary cause of the disease, and might explain why patients with severe pre-existing damage are much more likely to deteriorate even if their intraocular pressure is the same or lower than that of patients without visual loss at the time of diagnosis. The model can be used to screen compounds for their efficacy in protecting initially spared neurons from undergoing secondary degeneration, thereby achieving a better functional outcome. The findings obtained using this model support the attempt to develop neuroprotective therapy for glaucoma. Such therapy would need to be applied in combination with treatment (e.g., antihypertensive therapy) directed against the primary cause of the neuropathy.

Animals↗
PubMedDate not supplied

Optic nerve degeneration and potential neuroprotection: implications for glaucoma.

In order to study the course of optic nerve degeneration and devise possible ways to achieve neuroprotection, a well-controlled, animal model of partial crush injury of the optic nerve was used. Following the controlled partial crush injury of the rat optic nerve, quantitative morphological and electrophysiological measurements were made of primary and secondary neuronal losses. The neuroprotective effects of NMDA-receptor antagonists and alpha 2-adrenoreceptor agonists were also studied. The results suggested that the ongoing progression of the optic nerve degeneration in glaucoma might be a consequence of the toxic extracellular environment produced by neurons that degenerate as a result of the primary cause of the disease (such as increased IOP).

Action Potentials↗
PubMedDate not supplied

Effects of age on the metabolic, ionic and electrical responses to anoxia in the newborn dog brain in vivo.

The interrelation between brain energy metabolism, electrical activity and ion homeostasis developing under experimental anoxia in animals of different ages is of significant value in the understanding of brain damage occurring under similar conditions of clinical neuropathology. The purpose of the present study was to compare brain energy states and extracellular ion homeostasis during anoxia in newborn puppies of various ages. We have developed and used a multiparametric monitoring device by which various functions of the brain can be recorded in a real-time mode from a 5 mm diameter area on the surface of the cortex. Intracellular oxygen balance was evaluated in newborn puppies of various ages by monitoring the intramitochondrial NADH redox state using a fluorescence technique. The electrical activity was measured by recording the spontaneous ECoG (electrocorticogram) and DC (direct current) steady potential. Ion homeostasis was evaluated using surface potassium and calcium mini-electrodes. Newborn puppies were anesthetized, the dura mater was removed and the multiprobe assembly was placed on the brain and cemented to the skull. Five groups of puppies (0-1, 2-7, 8-14, 15-21 days and 3-24 weeks) were exposed to 5 minutes of complete O2 deprivation (100% nitrogen exposure) and were monitored during the recovery period until all parameters returned to baseline values. The results may be summarized as follows: 1. Resting baseline levels of extracellular K+ were in the same range as described for other young and adult mammals (2.9 +/- 0.05 mM). 2. Extracellular Ca2+ levels were higher than those published for other mammals (1.6 +/- 0.07 mM). 3. During 5 minutes of anoxia, a significant increase in K+ levels was recorded. This increase was not accompanied by measurable changes in extracellular Ca2+. 4. The effect of age on the length of time to the elevation of the extracellular K+ concentration and on the rate of K+ accumulation from the onset of the anoxic condition was significant, i.e., the younger the animal the longer the time and the lower the rate. 5. The rate of energy depletion was age dependent as indicated by the rate of NADH accumulation during anoxia. However, no significant effect of age on the basal aerobic metabolism was found as measured by the maximum percent increase of NADH during anoxia.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗