RESUMEN
The nicotinic axon reflex-mediated sudomotor response was studied in mice and rats by recording the impressions of sweat droplets made in silicone molds after local injection of nicotine, and compared with sweating induced by acetylcholine and pilocarpine. Nicotine failed to activate mouse plantar sweat glands at any of the concentrations used (from 3 x 10(-6) to 3 x 10(-1) M). On the contrary, both acetylcholine and pilocarpine produced a dose-dependent increase in the number of secreting sweat glands. The location of sweat glands reactive to pilocarpine and acetylcholine was similar and restricted to the pads near the site of injection. We conclude that the sudomotor axon reflex response mediated by nicotinic receptors is not present in the mouse and the rat.
Asunto(s)
Axones/efectos de los fármacos , Axones/fisiología , Receptores Nicotínicos/efectos de los fármacos , Receptores Nicotínicos/metabolismo , Glándulas Sudoríparas/efectos de los fármacos , Glándulas Sudoríparas/inervación , Sudoración/efectos de los fármacos , Sudoración/fisiología , Fibras Simpáticas Posganglionares/efectos de los fármacos , Fibras Simpáticas Posganglionares/fisiología , Acetilcolina/farmacología , Animales , Axones/ultraestructura , Femenino , Pie/anatomía & histología , Pie/inervación , Pie/fisiología , Humanos , Ratones , Agonistas Muscarínicos/farmacología , Nicotina/farmacología , Agonistas Nicotínicos/farmacología , Pilocarpina/farmacología , Ratas , Ratas Sprague-Dawley , Receptores Muscarínicos/efectos de los fármacos , Receptores Muscarínicos/metabolismo , Glándulas Sudoríparas/fisiología , Fibras Simpáticas Posganglionares/citología , Factores de Tiempo , Vasodilatadores/farmacologíaRESUMEN
Aging deeply influences several morphologic and functional features of the peripheral nervous system (PNS). Morphologic studies have reported a loss of myelinated and unmyelinated nerve fibers in elderly subjects, and several abnormalities involving myelinated fibers, such as demyelination, remyelination and myelin balloon figures. The deterioration of myelin sheaths during aging may be due to a decrease in the expression of the major myelin proteins (P0, PMP22, MBP). Axonal atrophy, frequently seen in aged nerves, may be explained by a reduction in the expression and axonal transport of cytoskeletal proteins in the peripheral nerve. Aging also affects functional and electrophysiologic properties of the PNS, including a decline in nerve conduction velocity, muscle strength, sensory discrimination, autonomic responses, and endoneurial blood flow. The age-related decline in nerve regeneration after injury may be attributed to changes in neuronal, axonal, Schwann cell and macrophage responses. After injury, Wallerian degeneration is delayed in aged animals, with myelin remnants accumulated in the macrophages being larger than in young animals. The interaction between Schwann cells and regenerative axons takes longer, and the amount of trophic and tropic factors secreted by reactive Schwann cells and target organs are lower in older subjects than they are in younger subjects. The rate of axonal regeneration becomes slower and the density of regenerating axons decrease in aged animals. Aging also determines a reduction in terminal and collateral sprouting of regenerated fibers, further limiting the capabilities for target reinnervation and functional restitution. These age-related changes are not linearly progressive with age; the capabilities for axonal regeneration and reinnervation are maintained throughout life, but tend to be delayed and less effective with aging.
Asunto(s)
Envejecimiento/fisiología , Regeneración Nerviosa/fisiología , Sistema Nervioso Periférico/fisiología , Animales , Humanos , Fibras Nerviosas/fisiologíaRESUMEN
We investigated the neuropathic effects of cisplatin in two groups of mice treated with 5 or 10 mg/kg/week of cisplatin for 7 or 8 weeks. Peripheral nerve functions were evaluated by sweat imprints, and electrophysiological, rotarod, and nociceptive tests. Protein gene product 9.5 (PGP), calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) were immunohistochemically localized in footpads. Tibial nerves were analyzed morphometrically. Functional deficits developed progressively with higher cumulative doses, more markedly in mice treated with high than in those with low doses. From cumulative doses of 10 mg/kg, significant declines in sensory nerve conduction velocity and sudomotor responses were found, whereas motor and nociceptive functions were involved later. There were no morphometrical changes in tibial nerves. A marked decrease of CGRP- and VIP-immunoreactive nerves occurred in samples from treated mice, whereas PGP-labeled profiles decreased mildly at late stages. Impairment of the content of neuropeptides with neurosecretor role was detectable earlier than functional abnormalities. Immunohistochemical analysis of skin biopsies offers a useful diagnostic tool for peripheral neuropathies.
Asunto(s)
Antineoplásicos , Cisplatino , Enfermedades del Sistema Nervioso/inducido químicamente , Enfermedades del Sistema Nervioso/fisiopatología , Animales , Péptido Relacionado con Gen de Calcitonina/metabolismo , Relación Dosis-Respuesta a Droga , Electrofisiología , Femenino , Inmunohistoquímica , Ratones , Actividad Motora/fisiología , Enfermedades del Sistema Nervioso/metabolismo , Nociceptores/fisiología , Sudoración/fisiología , Tioléster Hidrolasas/metabolismo , Ubiquitina Tiolesterasa , Péptido Intestinal Vasoactivo/metabolismoRESUMEN
Functional sudomotor responses have been studied in sweat glands reinnervated after sciatic nerve crush and partially denervated by cisplatin intoxication in the mouse. The sudomotor function mediated by the sciatic nerve was evaluated by silicone imprints on the plantar surface of the hindpaws. Five days after nerve crush, completely denervated sweat glands became unresponsive to cholinergic stimulation with pilocarpine. During the following weeks, the number of reinnervated, reactive sweat glands increased progressively to reach a maximum of 89% of preoperative control counts by 40 days after nerve crush. At this time, the mean volume of sweat secreted per gland was normal, but reinnervated glands showed a secretory activity abnormally sustained over time after pilocarpine stimulation and, on the other hand, had an increased resistance to the inhibition of secretion induced by atropine. The effects of cisplatin administration on sudomotor function were investigated in two groups of mice, one treated with high doses of cisplatin (10 mg/kg/week for 4 weeks) and another treated with low doses of cisplatin (5 mg/kg/week for 8 weeks). Cisplatin intoxication produced abnormal sudomotor responses indicative of denervation from cumulative doses of 10 mg/kg. The first abnormality found was a partial resistance of sweat glands to atropine, followed by a decrease in the sweat output per gland and finally a decline in the number of sweat glands activated by pilocarpine. These abnormalities in the sudomotor responses were more pronounced in mice treated with a high dose than in those with a lower dose regime.
Asunto(s)
Fibras Colinérgicas/fisiología , Regeneración Nerviosa/fisiología , Glándulas Sudoríparas/inervación , Animales , Antineoplásicos/farmacología , Atropina/farmacología , Sistema Nervioso Autónomo/efectos de los fármacos , Sistema Nervioso Autónomo/fisiología , Fibras Colinérgicas/efectos de los fármacos , Cisplatino/farmacología , Femenino , Ratones , Compresión Nerviosa , Parasimpatolíticos/farmacología , Parasimpaticomiméticos/farmacología , Pilocarpina/farmacología , Nervio Ciático/citologíaRESUMEN
We compared reinnervation of target organs after sciatic nerve section leaving gaps of 2, 4, 6, or 8 mm or gaps repaired with silicone tubes in different groups of mice. Functional reinnervation was assessed by noninvasive methods to determine recovery of sweating, nociceptive, and muscular functions in the hindpaw repeatedly during 3 months postoperation. The increase of gap length between nerve stumps delayed the beginning and reduced the degree of functional recovery achieved either with or without repair. When lesions were left unrepaired, functional reinnervation was only noticeable with a 2-mm gap and practically absent with longer gaps. With tube repair, reinnervation started earlier and achieved higher values than in the corresponding unrepaired groups. Tubulization was most effective with 4-mm gaps and comparatively less with shorter and longer gaps. With 4-mm gaps, recovery was higher when the silicone tube had a cross-sectional area 2.5 times that of the sciatic nerve than with narrower or wider tubes and when the wall was the thinnest available. In all cases muscle reinnervation showed a lower progression than sweating and nociceptive recovery.
Asunto(s)
Fibras Nerviosas/fisiología , Regeneración , Nervio Ciático/fisiología , Potenciales de Acción/fisiología , Animales , Femenino , Ratones , Ratones Endogámicos , Músculos/fisiologíaRESUMEN
This study evaluates the functional activity of the mouse sweat glands in response to cholinergic agonists and antagonists using the silicone imprint technique. In intact mice the response to acetylcholine, methacholine and pilocarpine did not differ significantly from control saline injection, indicating that immobilization induces high levels of sweating, masking the effects of cholinergic stimulation. Plantar emotional sweating was completely abolished by local anesthesia at the ankle. Under these conditions, administration of acetylcholine only provoked detectable sweating when injected locally into the sole skin. Methacholine activated an increasing number of sweat glands in a dose-dependent manner between 0.5 and 10 mg/kg; the response was maximal after 5-10 min of administration and decreased subsequently. With pilocarpine the maximum number of reactive sweat glands was observed at a dose of 2.5 mg/kg. The response was stable for 45 min with doses 2.5 and 5 mg/kg, but decreased exponentially with higher doses. The subtype of sweat gland muscarinic receptor was characterized by determining the inhibitory effect of different cholinergic antagonists on pilocarpine response. Atropine and 4-DAMP were equally potent inhibitors, showing a dose-related effect from 0.05 mg/kg. Pirenzepine only showed inhibitory effects with doses 10-times higher, whereas gallamine and hexamethonium did not induce inhibition at any of the doses tested. These findings suggest that the mouse eccrine sweat gland muscarinic receptors are predominantly M3.
Asunto(s)
Agonistas Colinérgicos/farmacología , Antagonistas Colinérgicos/farmacología , Glándulas Sudoríparas/efectos de los fármacos , Glándulas Sudoríparas/fisiología , Sudoración/efectos de los fármacos , Sudoración/fisiología , Animales , Relación Dosis-Respuesta a Droga , Femenino , Miembro Posterior , Ratones , Receptores Muscarínicos/efectos de los fármacosRESUMEN
The fibrinolytic activity in cerebrospinal fluid has been monitored by determination of levels of fibrin split products (FSP) in 23 patients with ruptured intracranial aneurysms. In 20 of these 23, FSP was found in the cerebrospinal fluid (CSF), with levels ranging from 10 to 80 micrograms/ml. Eleven of the 23 patients were treated with 2 gm tranexamic acid daily. In these patients FSP was found in only two cases during the 2nd week, while in 12 untreated patients it was found in 10 cases. These results suggest that there exists a localized fibrinolytic activity, and monitoring the FSP levels in the CSF may be a simple and accurate method for controlling the efficiency of antifibrinolytic therapy. Thus, treatment could be begun with a lower dose, which could be increased later as deemed necessary from the results of careful monitoring.