Co-treatment with riluzole and GDNF is necessary for functional recovery after ventral root avulsion injury

Bergerot, A

doi:10.1016/j.expneurol.2004.02.003

Cited by 85 publications

(80 citation statements)

References 44 publications

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“…A lessened neuroprotective effect, but not axonal reinnervation by surviving neurons, may be expected with delayed implantations, because previous studies have shown that only motoneuronal survival declined with increased delay of nerve implantation after avulsion . It is of interest to note that long-term neuroprotective effects by root implantations into the spinal cord are controversial, because some investigators have shown no motoneuronal protection at 3-4 months (Bergerot et al, 2004;Blits et al, 2004), whereas others have demonstrated a sustained improvement of motoneuronal survival at both 12 and 20 weeks after a cervical root implantation . Although we show a significant increase in cell survival, not all axotomized neurons were protected.…”

Section: Reinnervation Of the Lut Function After Injurymentioning

confidence: 99%

Functional Reinnervation of the Rat Lower Urinary Tract after Cauda Equina Injury and Repair

Hoang

Pikov²,

Havton³

2006

J. Neurosci.

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Conus medullaris and/or cauda equina forms of spinal cord injury commonly result in a permanent loss of bladder function. Here, we developed a cauda equina injury and repair rodent model to investigate whether surgical implantation of avulsed lumbosacral ventral roots into the spinal cord can promote functional recovery of the lower urinary tract. Adult female rats underwent sham surgery (n ϭ 6), bilateral L5-S2 ventral root avulsion (VRA) injury (n ϭ 5), or bilateral L5-S2 VRA followed by an acute implantation of the avulsed L6 and S1 ventral roots into the conus medullaris (n ϭ 6). At 12 weeks after operation, the avulsed group demonstrated urinary retention, absence of bladder contractions and external urethral sphincter (EUS) electromyographic (EMG) activation during urodynamic recordings, increased bladder size, and retrograde death of autonomic and motoneurons in the spinal cord. In contrast, the implanted group showed reduced urinary retention, return of reflexive bladder voiding contractions coincident with EUS EMG activation, anatomical reinnervation of the EUS demonstrated by retrograde neuronal labeling, normalization of bladder size, and a significant neuroprotection of both autonomic and motoneurons. In addition, a positive correlation between motoneuronal survival and voiding efficiency was observed in the implanted group. Our results show that implantation of avulsed lumbosacral ventral roots into the spinal cord promotes reinnervation of the urinary tract and return of functional micturition reflexes, suggesting that this surgical repair strategy may also be of clinical interest after conus medullaris and cauda equina injuries.

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Section: Reinnervation Of the Lut Function After Injurymentioning

confidence: 99%

Functional Reinnervation of the Rat Lower Urinary Tract after Cauda Equina Injury and Repair

Hoang

Pikov²,

Havton³

2006

J. Neurosci.

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“…Blockade of p75 with specific antibodies reverts the detrimental outcome induced by high doses of BDNF, and thus demonstrates a role of p75 in this effect [45]. Similarly to BDNF, GDNF can also support MN survival and regeneration [15,20,44,48]. In this case, mRNA levels of both GDNF receptors-high affinity receptor GFRa1 and low affinity receptor c-ret-increase in MN during some weeks after axotomy and avulsion lesions [44].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the lack of selective re-innervation of appropriate muscles by regenerating motor axons after severe nerve lesions, such as VRA, often impedes the coordinated muscle contractions needed for an adequate joint movement, despite good muscle reinnervation [58]. Slight functional recovery has been described with re-implantation after cervical spinal roots avulsion [11][12][13], but is very limited after lumbar root avulsion [15,48]. Two main factors are determinant of successful muscle re-innervation and functional recovery: the distance from the spinal cord to target muscles and the timedepending capacity of nerves to support axonal regeneration [17].…”

Section: Discussionmentioning

confidence: 99%

Neuroprotection and Axonal Regeneration After Lumbar Ventral Root Avulsion by Re-implantation and Mesenchymal Stem Cells Transplant Combined Therapy

et al. 2013

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Ventral spinal root avulsion causes complete denervation of muscles in the limb and also progressive death of segmental motoneurons (MN) leading to permanent paralysis. The chances for functional recovery after ventral root avulsion are very poor owing to the loss of avulsed neurons and the long distance that surviving neurons have to re-grow axons from the spinal cord to the corresponding targets. Following unilateral avulsion of L4, L5 and L6 spinal roots in adult rats, we performed an intraspinal transplant of mesenchymal stem cells (MSC) and surgical re-implantation of the avulsed roots. Four weeks after avulsion the survival of MN in the MSC-treated animals was significantly higher than in vehicle-injected rats (45 % vs 28 %). Re-implantation of the avulsed roots in the injured spinal cord allowed the regeneration of motor axons. By combining root re-implantation and MSC transplant the number of surviving MN at 28 days post-injury was higher (60 %) than in re-implantation alone animals (46 %). Electromyographic tests showed evidence of functional re-innervation of anterior tibialis and gastrocnemius muscles by the regenerated motor axons only in rats with the combined treatment. These results indicate that MSC are helpful in enhancing neuronal survival and increased the regenerative growth of injured axons. Surgical re-implantation and MSC grafting combined had a synergic neuroprotective effect on MN and on axonal regeneration and muscle re-innervation after spinal root avulsion.

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“…1,5 Several animal models have been developed to investigate various SCI mechanisms, most commonly in adult rats. Such models apply mechanical force to the spinal cord of anesthetized animals, including compression, 6 spinal root avulsion, 7,8 laceration, 9 etc. These models allow the effects of mechanical injury on neuronal damage and subsequent recovery to be studied under controlled conditions.…”

Section: Introductionmentioning

confidence: 99%

Perfusion assessment in rat spinal cord tissue using photoplethysmography and laser Doppler flux measurements

Phillips¹,

Cibert-Goton²,

Langford³

et al. 2013

J. Biomed. Opt

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This is the published version of the paper.This version of the publication may differ from the final published version. Abstract. Animal models are widely used to investigate the pathological mechanisms of spinal cord injury (SCI), most commonly in rats. It is well known that compromised blood flow caused by mechanical disruption of the vasculature can produce irreversible damage and cell death in hypoperfused tissue regions and spinal cord tissue is particularly susceptible to such damage. A fiberoptic photoplethysmography (PPG) probe and instrumentation system were used to investigate the practical considerations of making measurements from rat spinal cord and to assess its suitability for use in SCI models. Experiments to assess the regional perfusion of exposed spinal cord in anesthetized adult rats using both PPG and laser Doppler flowmetry (LDF) were performed. It was found that signals could be obtained reliably from all subjects, although considerable intersite and intersubject variability was seen in the PPG signal amplitude compared to LDF. We present results from 30 measurements in five subjects, the two methods are compared, and practical application to SCI animal models is discussed. Permanent repository link

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Co-treatment with riluzole and GDNF is necessary for functional recovery after ventral root avulsion injury

Cited by 85 publications

References 44 publications

Functional Reinnervation of the Rat Lower Urinary Tract after Cauda Equina Injury and Repair

Functional Reinnervation of the Rat Lower Urinary Tract after Cauda Equina Injury and Repair

Neuroprotection and Axonal Regeneration After Lumbar Ventral Root Avulsion by Re-implantation and Mesenchymal Stem Cells Transplant Combined Therapy

Perfusion assessment in rat spinal cord tissue using photoplethysmography and laser Doppler flux measurements

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