Recovery of respiratory activity after C2 hemisection (C2HS): Involvement of adenosinergic mechanisms

Nantwi, Kwaku D.

doi:10.1016/j.resp.2009.07.014

Cited by 10 publications

(7 citation statements)

References 85 publications

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“…1,2 These pathways monosynaptically 23,24 or polysynaptically (via spinal interneurons 6,22,25,26 ) innervate PhMNs ipsilateral to injury, restoring inspiratory drive and phrenic motor output. Several studies have also shown that this plasticity is regulated by serotonin, 27,28 adenosine, 29 and glutamate. 28,30,31 Although acute activation of the CPP supports the presence of an existing latent pathway, previous studies have also revealed that ongoing neuroanatomical reorganization and recruitment of polysynaptic pathways associated with the sCPP likely contribute to further changes within crossed-phrenic pathways and long-term recovery.…”

Section: Discussionmentioning

confidence: 96%

Anatomical Recruitment of Spinal V2a Interneurons into Phrenic Motor Circuitry after High Cervical Spinal Cord Injury

Zholudeva

Karliner

Dougherty

et al. 2017

Journal of Neurotrauma

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More than half of all spinal cord injuries (SCIs) occur at the cervical level, often resulting in impaired respiration. Despite this devastating outcome, there is substantial evidence for endogenous neuroplasticity after cervical SCI. Spinal interneurons are widely recognized as being an essential anatomical component of this plasticity by contributing to novel neuronal pathways that can result in functional improvement. The identity of spinal interneurons involved with respiratory plasticity post-SCI, however, has remained largely unknown. Using a transgenic Chx10-eGFP mouse line (Strain 011391-UCD), the present study is the first to demonstrate the recruitment of excitatory interneurons into injured phrenic circuitry after a high cervical SCI. Diaphragm electromyography and anatomical analysis were used to confirm lesion-induced functional deficits and document extent of the lesion, respectively. Transneuronal tracing with pseudorabies virus (PRV) was used to identify interneurons within the phrenic circuitry. There was a robust increase in the number of PRV-labeled V2a interneurons ipsilateral to the C2 hemisection, demonstrating that significant numbers of these excitatory spinal interneurons were anatomically recruited into the phrenic motor pathway two weeks after injury, a time known to correspond with functional phrenic plasticity. Understanding this anatomical spinal plasticity and the neural substrates associated with functional compensation or recovery post-SCI in a controlled, experimental setting may help shed light onto possible cellular therapeutic candidates that can be targeted to enhance spontaneous recovery.

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Section: Discussionmentioning

confidence: 96%

Anatomical Recruitment of Spinal V2a Interneurons into Phrenic Motor Circuitry after High Cervical Spinal Cord Injury

Zholudeva

Karliner

Dougherty

et al. 2017

Journal of Neurotrauma

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“…This model is currently used by several laboratories around the world (for reviews: [4][5][6][7][8][9][10][11][12][13] ). However, slight differences in the surgical procedure can be observed among the different investigators to generate this particular cervical injury murine model.…”

Section: Introductionmentioning

confidence: 99%

A Murine Model of Cervical Spinal Cord Injury to Study Post-lesional Respiratory Neuroplasticity

Keomani

Deramaudt

Petitjean

et al. 2014

JoVE

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Citation: Keomani, E., Deramaudt, T.B., Petitjean, M., Bonay, M., Lofaso, F., Vinit, S. A Murine Model of Cervical Spinal Cord Injury to Study Postlesional Respiratory Neuroplasticity. J. Vis. Exp. (87), e51235, doi:10.3791/51235 (2014). AbstractA cervical spinal cord injury induces permanent paralysis, and often leads to respiratory distress. To date, no efficient therapeutics have been developed to improve/ameliorate the respiratory failure following high cervical spinal cord injury (SCI). Here we propose a murine pre-clinical model of high SCI at the cervical 2 (C2) metameric level to study diverse post-lesional respiratory neuroplasticity. The technique consists of a surgical partial injury at the C2 level, which will induce a hemiparalysis of the diaphragm due to a deafferentation of the phrenic motoneurons from the respiratory centers located in the brainstem. The contralateral side of the injury remains intact and allows the animal recovery. Unlike other SCIs which affect the locomotor function (at the thoracic and lumbar level), the respiratory function does not require animal motivation and the quantification of the deficit/recovery can be easily performed (diaphragm and phrenic nerve recordings, whole body ventilation). This preclinical C2 SCI model is a powerful, useful, and reliable pre-clinical model to study various respiratory and non-respiratory neuroplasticity events at different levels (molecular to physiology) and to test diverse putative therapeutic strategies which might improve the respiration in SCI patients. Video LinkThe video component of this article can be found at

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“…In non-toxic concentrations, the methylxanthines caffeine and theophylline are non-selective antagonists of the adenosine receptors (Fredholm, 2007, Fredholm, et al, 1999). Clinically, apnea of prematurity can be treated effectively with caffeine (Schmidt, et al, 2007); likewise, inhibition of adenosine receptors with theophylline was shown to restore spontaneous respiration after spinal cord injury (Nantwi, 2009). Thus, methylxanthines can be used experimentally and therapeutically to influence adenosine-based modulation of respiratory function.…”

Section: Introductionmentioning

confidence: 99%

Caffeine prevents acute mortality after TBI in rats without increased morbidity

Lusardi

Lytle

Szybala

et al. 2012

Experimental Neurology

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Severe traumatic brain injury (TBI) is associated with a high incidence of acute mortality followed by chronic alteration of homeostatic network activity that includes the emergence of posttraumatic seizures. We hypothesized that acute and chronic outcome after severe TBI critically depends on disrupted bioenergetic network homeostasis, which is governed by the availability of the brain’s endogenous neuroprotectant adenosine. We used a rat lateral fluid percussion injury (FPI) model of severe TBI with an acute mortality rate of 46.7%. A subset of rats was treated with 25 mg/kg caffeine intraperitoneally within 1 minute of the injury. We assessed neuromotor function at 24 hours and 4 weeks, and video-EEG activity and histology at 4 weeks following injury. We first demonstrate that acute mortality is related to prolonged apnea and that a single acute injection of the adenosine receptor antagonist caffeine can completely prevent TBI-induced mortality when given immediately following the TBI. Second, we demonstrate that neuromotor function is not affected by caffeine treatment at either 24 hours or 4 weeks following injury. Third, we demonstrate development of epileptiform EEG bursts as early as 4 weeks post-injury that are significantly reduced in duration in the rats that received caffeine. Our data demonstrate that acute treatment with caffeine can prevent lethal apnea following fluid percussion injury, with no negative influence on motor function or histological outcome. Further, we show epileptiform bursting is reduced after caffeine treatment, suggesting a potential role in the modulation of epilepsy development after severe injury.

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Recovery of respiratory activity after C2 hemisection (C2HS): Involvement of adenosinergic mechanisms

Cited by 10 publications

References 85 publications

Anatomical Recruitment of Spinal V2a Interneurons into Phrenic Motor Circuitry after High Cervical Spinal Cord Injury

Anatomical Recruitment of Spinal V2a Interneurons into Phrenic Motor Circuitry after High Cervical Spinal Cord Injury

A Murine Model of Cervical Spinal Cord Injury to Study Post-lesional Respiratory Neuroplasticity

Caffeine prevents acute mortality after TBI in rats without increased morbidity

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