Transplantation of embryonic noradrenergic neurons in two models of adult rat spinal cord injury: ultrastructural immunocytochemical study

Ribotta, Minerva Giménez y; Roudet, C.; Sandillon, F.; Privat, Alain

doi:10.1016/0006-8993(95)01266-4

Cited by 15 publications

(17 citation statements)

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“…Administration of both noradrenaline and its agonists also elicit and maintain fictive locomotion in the neonatal spinal cord in vitro (Kiehn et al, 1999; Sqalli-Houssaini and Cazalets, 2000). Furthermore, transplantation of embryonic locus coeruleus tissue into the spinal cord caudal to the lesion, i.e., caudal stump, in adult spinal rats reinnervates previous targets (Gimenez y Ribotta et al, 1996) and leads to improved hindlimb stepping (Yakovleff et al, 1989; Gimenez y Ribotta et al, 1998a; Gimenez y Ribotta et al, 1998b) and recovery of withdrawal reflexes (Moorman et al, 1990). NA α1- and α2-receptors are expressed broadly throughout the gray mater in an intact spinal cord and are up-regulated in the lumbar segments after a complete spinal cord transection (Roudet et al, 1994; Roudet et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Noradrenergic innervation of the rat spinal cord caudal to a complete spinal cord transection: Effects of olfactory ensheathing glia

Takeoka

Kubasak

Zhong³

et al. 2010

Experimental Neurology

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Transplantation of olfactory bulb-derived olfactory ensheathing glia (OEG) combined with step training improves hindlimb locomotion in adult rats with a complete spinal cord transection. Spinal cord injury studies use the presence of noradrenergic (NA) axons caudal to the injury site as evidence of axonal regeneration and we previously found more NA axons just caudal to the transection in OEG- than media-injected spinal rats. We therefore hypothesized that OEG transplantation promotes descending coeruleospinal regeneration that contributes to the recovery of hindlimb locomotion. Now we report that NA axons are present throughout the caudal stump of both media- and OEG-injected spinal rats and they enter the spinal cord from the periphery via dorsal and ventral roots and along large penetrating blood vessels. These results indicate that the presence of NA fibers in the caudal spinal cord is not a reliable indicator of coeruleospinal regeneration. We then asked if NA axons appose cholinergic neurons associated with motor functions, i.e., central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more NA varicosities adjacent to central canal cluster cells, partition cells, and SMNs in the lumbar enlargement of OEG- than media-injected rats. As non-synaptic release of NA is common in the spinal cord, more associations between NA varicosities and motor-associated cholinergic neurons in the lumbar spinal cord may contribute to the improved treadmill stepping observed in OEG-injected spinal rats. This effect could be mediated through direct association with SMNs and/or indirectly via cholinergic interneurons.

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Section: Introductionmentioning

confidence: 99%

Noradrenergic innervation of the rat spinal cord caudal to a complete spinal cord transection: Effects of olfactory ensheathing glia

Takeoka

Kubasak

Zhong³

et al. 2010

Experimental Neurology

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“…In vivo models are important because they permit the measurement of the physiologic, or pathophysiologic, and neurobehavioral responses of whole animals due to trauma (Morrison et al 1998b). However, the complexity of in vivo scenarios can confound the interpretation of the response of the spinal cord to mechanical trauma (Chernoff 1996;Gimenez Y Ribotta et al 1996;Campagnolo et al 2000;Tsuda et al 2005;Ohlsson et al 2006;Pan and Kastin 2008). In vitro models of SCI in neuronal cells provide an opportunity to control and simplify the complex environment that accompanies SCI, yielding information about cellular metabolism and function that is difficult to obtain in vivo.…”

Section: Discussionmentioning

confidence: 99%

Establishment and assessment of a simple and easily reproducible incision model of spinal cord neuron cells in vitro

Que

Liu

Jia

et al. 2011

In Vitro Cell.Dev.Biol.-Animal

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A growing number of in vitro models have been introduced to study the mechanisms of spinal cord injury. A potential drawback of these models is that they are difficult to reproduce. In this study, an in vitro incision model was established using primary cultured neuronal cells from fetal rat spinal cords. The neurons were subjected to incision in a simple and reproducible way. To assess whether this model could simulate the responses of spinal cord neuron cells in vivo after a spinal cord transection, apoptosis, and the expression of immediate early genes were detected in the neurons at various time points after injury. The results indicated that: (1) significantly more terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells were observed at 1, 3, and 7 d following injury and (2) the expression of both c-Jun and c-Fos was induced 10 min after incision and had markedly higher levels 2 h post-injury. These results suggested that our model can partially imitate the responses of in vivo neuronal cells after a spinal cord transection and such models may facilitate further understanding of biochemical and cellular events associated with spinal cord injury.

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“…1986; Yakovleff et al . 1995; Giménez y Giménez y Ribotta et al . 1996), intraspinally grafted LC neurons gave rise to rich DBH‐immunoreactive fibre networks, which extended for several millimeters within the previously denervated host's target regions and reinstated noradrenergic terminal innervation up to near‐normal density (80%).…”

Section: Discussionmentioning

confidence: 99%

“…1995; Yakovleff et al . 1995; Giménez y Giménez y Ribotta et al . 1996), cannot be completely ruled out.…”

Section: Discussionmentioning

confidence: 99%

“…see Leanza et al . 1993; Giménez y Giménez y Ribotta et al . 1996), the lesioned rats were randomly allocated into four groups: lesioned controls ( n = 8), lesioned and grafted with embryonic locus coeruleus (LC, n = 10), lesioned and grafted with adrenal medulla (AM, n = 7), lesioned and grafted with autologous superior cervical ganglion (SCG, n = 7).…”

Section: Methodsmentioning

confidence: 99%

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Release properties and functional integration of noradrenergic‐rich tissue grafted to the denervated spinal cord of the adult rat

Leanza

Cataudella

Dimauro

et al. 1999

Eur J of Neuroscience

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Noradrenaline- (NA-) containing grafts of central (embryonic locus coeruleus, LC) or peripheral (juvenile adrenal medullary, AM, autologous superior cervical ganglionic, SCG) tissue were implanted unilaterally into rat lumbar spinal cord previously depleted of its NA content by 6-hydroxydopamine (6-OHDA) intraventricularly. A microdialysis probe was implanted in the spinal cord 3-4 months after transplantation, and extracellular levels of noradrenaline were monitored in freely moving animals during basal conditions and following administration of pharmacological or behavioural stimuli. Age-matched normal and lesioned animals both served as controls. Morphometric analyses were carried out on horizontal spinal sections processed for dopamine-beta-hydroxylase (DBH) immunocitochemistry, in order to assess lesion- or graft-induced changes in the density of spinal noradrenergic innervation, relative to the normal patterns. In lesioned animals, the entire spinal cord was virtually devoid of DBH-positive fibers, resulting in a dramatic 88% reduction in baseline NA, compared with that in controls, which did not change in response to the various stimuli. LC and SCG grafts reinstated approximately 80% and 50% of normal innervation density, respectively, but they differed strikingly in their release ability. Thus, LC grafts restored baseline NA levels up to 60% of those in controls, and responded with significantly increased NA release to KCl-induced depolarization, neuronal uptake blockade and handling. In contrast, very low NA levels and only poor and inconsistent responses to the various stimuli were observed in the SCG-grafted animals. In AM-grafted animals, spinal extracellular NA levels were restored up to 45% of those in controls, probably as a result of nonsynaptic, endocrine-like release, as grafted AM cells retained the chromaffine phenotype, showed no detectable fibre outgrowth and did not respond to any of the pharmacological or behavioural challenges. Thus, both a regulated, impulse-dependent, and a diffuse, paracrine-like, NA outflow may play roles in the recovery of lesion-induced sensory and/or motor impairments previously reported with these types of grafts following transplantation into the severed spinal cord.

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Transplantation of embryonic noradrenergic neurons in two models of adult rat spinal cord injury: ultrastructural immunocytochemical study

Cited by 15 publications

References 50 publications

Noradrenergic innervation of the rat spinal cord caudal to a complete spinal cord transection: Effects of olfactory ensheathing glia

Noradrenergic innervation of the rat spinal cord caudal to a complete spinal cord transection: Effects of olfactory ensheathing glia

Establishment and assessment of a simple and easily reproducible incision model of spinal cord neuron cells in vitro

Release properties and functional integration of noradrenergic‐rich tissue grafted to the denervated spinal cord of the adult rat

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