Mechanisms of the inhibition of fast axonal transport by local anesthetics

Lavoie, P.‐A.; Khazen, T.; Filion, Pierre

doi:10.1016/0028-3908(89)90054-3

Cited by 82 publications

(68 citation statements)

References 27 publications

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“…The effects of lidocaine and related molecules on axonal transport are well documented in the literature (Fink et al, 1972;Byers et al, 1973;Bisby, 1975;Fink and Kish, 1976;Lavoie et al, 1989). Lidocaine is believed to produce its inhibitory effect by an uncoupling of oxidative phosphorylation (Haschke and Fink, 1975), with a consequent interruption of ATP supply to the transport mechanism.…”

Section: Effects Of Injury and Trophic Deprivation On Rgc Survivalmentioning

confidence: 96%

Axonal Transport Blockade in the Neonatal Rat Optic Nerve Induces Limited Retinal Ganglion Cell Death

et al. 1997

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Optic nerve section in the newborn rat results in a rapid apoptotic degeneration of most axotomized retinal ganglion cells (RGCs). This massive process of neuronal death has been ascribed mainly to the interruption of a trophic factor supply from target structures rather than to the axonal damage per se. To distinguish between these two possibilities, we induced a reversible axonal transport blockade in the developing optic nerve by topical application of a local anesthetic (lidocaine). Light and electron microscopy showed no alterations in the fine structure of treated optic nerves. Retinae of treated and control rats were stained with cresyl violet and examined at different times after surgery. We found that axonal transport blockade induced only a limited number of pyknotic RGCs. Degeneration of these cells was completely prevented by inhibiting protein synthesis during lidocaine application. We conclude that the rapid degeneration of RGCs after axotomy can be ascribed only partly to the loss of retrogradely transported trophic factors.Key words: neuronal death; axonal transport; retinal ganglion cells; apoptosis; rat optic nerve; retrograde degenerationRetinal ganglion cells (RGC s), as well as other mammalian CNS neurons, eventually die as a result of axonal injury (Grafstein and Ingoglia, 1982;Bregman and Reier, 1986;Hefti, 1986; VillegasPerez et al., 1993). Transection of the optic nerve is known to induce massive RGC death by an apoptotic process in both developing (Rabacchi et al., 1994a) and adult rats (Berkelaar et al., 1994;Garcia-Valenzuela et al., 1994). The molecular nature of the signal triggering the loss of axotomized neurons is largely unknown. According to the trophic theory, the effects of axotomy can be ascribed to the disconnection of neurons from their targets, resulting in the sudden loss of retrogradely transported trophic molecules (Oppenheim, 1991;Snider et al., 1992;Johnson and Deckwerth, 1993). An alternative hypothesis is that axonal injury per se can induce cell death. In particular, acute alterations in cellular homeostasis and ionic imbalances subsequent to plasmalemmal leakage, such as C a 2ϩ deregulation, have been implicated (Choi, 1992;Snider et al., 1992).Especially in the neonate, a lack of target-derived trophic signals is proposed as the main cause of death for axotomized RGC s. It is known that trophic factors, such as NGF and BDNF, are synthesized in the major retinal projection fields, the optic tectum (Hofer et al., 1990;Maisonpierre et al., 1990;Friedman et al., 1991) and the dorsal lateral geniculate nucleus (dLGN) (Schoups et al., 1995). E xogenous administration of NGF and BDN F, as well as other growth factors, can partly prevent RGC death after optic nerve lesion (C armignoto et al., 1989;Mey and Thanos, 1993;Cohen et al., 1994;Mansour-Robaey et al., 1994;Rabacchi et al., 1994b). Moreover, the survival of highly purified RGCs in culture can be enhanced by both tectal cells (McCaffery et al., 1982;Armson and Bennett, 1983) and soluble tectal factors (Meyer-Fran...

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Section: Effects Of Injury and Trophic Deprivation On Rgc Survivalmentioning

confidence: 96%

Axonal Transport Blockade in the Neonatal Rat Optic Nerve Induces Limited Retinal Ganglion Cell Death

et al. 1997

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“…Monensin, a compound that inhibits acidification of intracellular organelles to prevent endocytosis and delivery of macromolecules to lysosomes, had no effect on albumin transport (Hastings et al, 1994). Lidocaine, which acts on axons of sensory neurons to block the conduction of action potentials by closing voltage-dependent Na 1 channels, has an attenuating effect on transport of materials in axons but had no effect on albumin (Lavoie et al, 1989;Hiruma et al, 2008). Also, vasogenic agents, such as histamine, did not increase transport of albumin, despite increasing BBB permeability (Stamatovic et al, 2008).…”

Section: Brain Uptake Of Intranasal Albuminmentioning

confidence: 99%

Intranasal Administration as a Route for Drug Delivery to the Brain: Evidence for a Unique Pathway for Albumin

Falcone

Salameh

Xiang³

et al. 2014

J Pharmacol Exp Ther

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“…En estudios en el nervio ciático de conejo y en la corteza cerebral de rata, se encontró que la procaína interactúa con las proteínas de los MT reduciendo la densidad de éstos en los axones (9,10). Otros trabajos revelaron que los anestésicos locales también disminuyen la densidad de los MT en los axones sin mielina (33).…”

Section: Anestésicos Localesunclassified

“…Se sabe que la propagación de señales en los MT depende de las propiedades eléctricas del medio en que están inmersos, particularmente de la permitividad, pero no hay estudios sistemáticos sobre la alteración de esta propiedad por la inclusión de anestésicos locales en el medio. Algunos resultados revelan que la presencia de anestésicos locales en el citosol disminuye la densidad de los MT en la fibra y también disminuye el transporte axónico (9). En otros casos no hay modificación en la densidad de los MT pero sí se observa disminución en el transporte axónico (10).…”

Section: Introductionunclassified

Microtúbulos y terapia neural: propuesta de una investigación promisoria

Cruz

Fayad

2011

Rev. Med.

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<p>La terapia neural es una práctica médica no convencional en la cual se inyectan anestésicos locales (procaína o lidocaína) en concentraciones en un rango de 1 – 10 mg/ml, en cantidades entre 1-10 cm3, en diferentes partes del cuerpo con fines terapéuticos mas no anestésicos. El mecanismo de acción de los anestésicos locales en esta terapia no se conoce. La posible acción remota de la procaína, el efecto de sus propiedades eléctricas en el transporte de señales en el sistema nervioso y en el restablecimiento del potencial fisiológico de membrana son temas centrales de la terapia neural que requieren una interpretación físico-química. En este artículo proponemos que la propagación de señales en microtúbulos neuronales podría estar involucrada en los mecanismos de acción de la procaína en terapia neural. Sugerimos algunos estudios experimentales que conduzcan a una interpretación científica rigurosa de las observaciones reportadas y de los efectos remotos que se atribuyen a la inyección de procaína en terapia neural.</p>

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Mechanisms of the inhibition of fast axonal transport by local anesthetics

Cited by 82 publications

References 27 publications

Axonal Transport Blockade in the Neonatal Rat Optic Nerve Induces Limited Retinal Ganglion Cell Death

Axonal Transport Blockade in the Neonatal Rat Optic Nerve Induces Limited Retinal Ganglion Cell Death

Intranasal Administration as a Route for Drug Delivery to the Brain: Evidence for a Unique Pathway for Albumin

Microtúbulos y terapia neural: propuesta de una investigación promisoria

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