Delayed riluzole treatment is able to rescue injured rat spinal motoneurons

Nógrádi, Antal; Szabó, Angela E.; Pintér, Sándor; Vrbová, Gerta

doi:10.1016/j.neuroscience.2006.09.046

Cited by 55 publications

(63 citation statements)

References 28 publications

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“…Experimental studies in rats showed significant improvements of neuronal sparing and reinnervating capacity after SCI. 43 Yet, although it would seem that they are easier to carry out, considering riluzole is in clinical use, no clinical trials have been conducted for this drug in SCI. 44 …”

Section: -Aminopyridine (Fampridine)mentioning

confidence: 99%

A review of published reports on neuroprotection in spinal cord injury

et al. 2009

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Study design: Literature review. Objectives: To review the main published current neuroprotection research trends and results in spinal cord injury (SCI). Setting: This paper is the result of a collaboration between a group of European scientists. Methods: Recent studies, especially in genetic, immune, histochemical and bio (nano)-technological fields, have provided new insight into the cellular and molecular mechanisms occurring within the central nervous system (NS), including SCIs. As a consequence, a new spectrum of therapies aiming to antagonize the 'secondary injury' pathways (that is, to provide neuroprotection) and also to repair such classically irreparable structures is emerging. We reviewed the most significant published works related to such novel, but not yet entirely validated, clinical practice therapies. Results: There have been identified many molecules, primarily expressed by heterogenous glial and neural subpopulations of cells, which are directly or indirectly critical for tissue damaging/sparing/ re-growth inhibiting, angiogenesis and neural plasticity, and also various substances/energy vectors with regenerative properties, such as MAG (myelin-associated glycoprotein), Omgp (oligodendrocyte myelin glycoprotein), KDI (synthetic: Lysine-Asparagine-Isoleucine 'g-1 of Laminin Kainat Domain'), Nogo (Neurite outgrowth inhibitor), NgR (Nogo protein Receptor), the Rho signaling pathway (superfamily of 'Rho-dopsin geneFincluding neurotransmitterFreceptors'), EphA4 (Ephrine), GFAP (Glial Fibrillary Acidic Protein), different subtypes of serotonergic and glutamatergic receptors, antigens, antibodies, immune modulators, adhesion molecules, scavengers, neurotrophic factors, enzymes, hormones, collagen scar inhibitors, remyelinating agents and neurogenetic/plasticity inducers, all aiming to preserve/re-establish the morphology and functional connections across the lesion site. Accordingly, modern research and experimental SCI therapies focus on several intricate, rather overlapping, therapeutic objectives and means, such as neuroprotective, neurotrophic, neurorestorative, neuroreparative, neuroregenerative, neuro(re)constructive and neurogenetic interventions. Conclusion: The first three of these therapeutical directions are generically assimilated as neuroprotective, and are synthetically presented and commented in this paper in an attempt to conceptually systematize them; thus, the aim of this article is, by emphasizing the state-of-the art in the domain, to optimize theoretical support in selecting the most effective pharmacological and physical interventions for preventing, as much as possible, paralysis, and for maximizing recovery chances after SCI.

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Section: -Aminopyridine (Fampridine)mentioning

confidence: 99%

A review of published reports on neuroprotection in spinal cord injury

et al. 2009

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“…It has been shown, that reimplantion of an avulsed root combined with the treatment of the anti-excitotoxic compound riluzole (2-amino-6-trifluoromethoxybenzothiazole) rescued the majority of the injured motoneurons otherwise destined to die (Nógrádi and Vrbová 2001;Nógrádi et al, 2007;Pintér et al, 2010). Earlier studies have shown that riluzole not only prevented the death of the damaged lumbar and cervical motoneurons but also enabled them to regenerate their axons into the reimplanted ventral root and thus provided functional reinnervation for the denervated limb musculature (Nógrádi et al, 2007, Pintér et al, 2010.…”

Section: Experimental Therapeutic Approaches To Prevent Motoneuron Lomentioning

confidence: 99%

“…Earlier studies have shown that riluzole not only prevented the death of the damaged lumbar and cervical motoneurons but also enabled them to regenerate their axons into the reimplanted ventral root and thus provided functional reinnervation for the denervated limb musculature (Nógrádi et al, 2007, Pintér et al, 2010.…”

Section: Experimental Therapeutic Approaches To Prevent Motoneuron Lomentioning

confidence: 99%

“…To avoid double counting of neurons present in consecutive sections, the retrogradely labelled neurons were mapped with the aid of an Olympus (Olympus Ltd, Tokyo, Japan) drawing tube, and their locations were compared with those of the labelled neurons in the previous section. All sections from the L4 motoneuron pool were used (Nógrádi et al, 2007).…”

Section: Cell Countsmentioning

confidence: 99%

“…It is thought that the diffusible factors produced by the grafts may reach the furthermost parts of the L4 segment, no matter whether they are secreted by an intraspinal or by an intraradicular graft. It has been reported that motoneurons after avulsion injury are responding to rescuing strategies if the treatment starts within 10 days following avulsion (Nógrádi et al, 2007). Therefore it appears likely that appropriate numbers of stem cells Transplantation of stem or neural progenitor cells (Hell et al 2009, Su et al 2009) producing neurotrophic factors or viral-based overexpression of BDNF or GDNF in the spinal cord or in the reimplanted ventral root (Blits et al, 2004, Eggers et al, 2008 induced prominent survival of damaged motoneurons with avulsed axons, but these rescued motoneurons were unable to send their axons into the reimplanted roots due to the enormous sprouting of regenerating axons.…”

Section: Function-blocking Antibodies Abolish the Neuroprotective Effmentioning

confidence: 99%

See 2 more Smart Citations

The effect of grafted neuroectodermal stem cells on injured spinal motoneurons following ventral root avulsion and reimplantation: insights into the molecular mechanism

Pajer¹

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The rocky road to translation in spinal cord repair

Filli

Schwab

2012

Annals of Neurology

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Over the past 2 decades, the biological understanding of the mechanisms underlying structural and functional repair of the injured central nervous system has strongly increased. This has resulted in the development of multiple experimental treatment strategies with the collective aim of enhancing and surpassing the limited spontaneous recovery occurring in animal models and ultimately humans suffering from spinal cord or brain injuries. Several of these experimental treatments have revealed beneficial effects in animal models of spinal cord injury. With the exception of neurorehabilitative therapies, however, therapeutic interventions that enhance recovery are currently absent within the clinical realm of spinal cord injury. The present review surveys the prospects and challenges in experimental and clinical spinal cord repair. Major shortcomings in experimental research center on the difficulty of closely modeling human traumatic spinal cord injury in animals, the small number of investigations done on cervical spinal injury and tetraplegia, and the differences in lesion models, species, and functional outcome parameters used between laboratories. The main challenges in the clinical field of spinal cord repair are associated with the standardization and sensitivity of functional outcome measures, the definition of the inclusion/exclusion criteria for patient recruitment in trials, and the accuracy and reliability of an early diagnosis to predict subsequent neurological outcome. Research and clinical networks were recently created with the goal of optimizing animal studies and human trials. Promising clinical trials are currently in progress. The time has come to translate the biologic-mechanistic knowledge from basic science into efficacious treatments able to improve the conditions of humans suffering from spinal cord injury.

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Delayed riluzole treatment is able to rescue injured rat spinal motoneurons

Cited by 55 publications

References 28 publications

A review of published reports on neuroprotection in spinal cord injury

A review of published reports on neuroprotection in spinal cord injury

The effect of grafted neuroectodermal stem cells on injured spinal motoneurons following ventral root avulsion and reimplantation: insights into the molecular mechanism

The rocky road to translation in spinal cord repair

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