Cervical Spinal Contusion Research Articles

Comorbidity of cardiorespiratory and locomotor dysfunction following cervical spinal cord injury in the rat.

Cervical spinal cord injury interrupts supraspinal pathways innervating thoracic sympathetic preganglionic neurons and results in cardiovascular dysfunction. Both respiratory and locomotor functions were also impaired due to damages of motoneuron pools controlling respiratory and forelimb muscles, respectively. However, no study has investigated autonomic and somatic motor functions in the same animal model. The present study aimed to establish a cervical spinal cord injury model to evaluate cardiorespiratory response and locomotor activity in unanesthetized rats. Cardiovascular response and respiratory behavior following laminectomy or cervical spinal contusion were measured using noninvasive blood pressure analyzer and plethysmography systems, respectively. Locomotor activity was evaluated by an open-field test and a locomotor rating scale. The results demonstrated that mean arterial blood pressure and heart rate were significantly reduced in contused rats compared with uninjured rats at the acute injured stage. Tidal volume was also significantly reduced during the acute and subchronic stages. Moreover, locomotor function was severely impaired, evidenced by decreasing moving ability and locomotor rating scores from the acute to chronic injured stages. Retrograde neurotracer results revealed that cervical spinal cord injury caused a reduction in number of phrenic and triceps motoneurons. Immunofluorescence staining revealed a significant attenuation of serotonergic, noradrenergic, glutamatergic, and GABAergic fibers innervating the thoracic sympathetic preganglionic neurons in chronically contused rats. These results revealed the pathological mechanism underlying the comorbidity of cardiorespiratory and locomotor dysfunction following cervical spinal cord injury. We proposed that this animal model can be used to evaluate the therapeutic efficacy of potential strategies to improve different physiological functions.NEW & NOTEWORTHY The present study establishes a preclinical rodent model to comprehensively investigate physiological functions under unanesthetized condition following cervical spinal cord contusion. The results demonstrated that cervical spinal cord contusion is associated with impairments in cardiovascular, respiratory, and locomotor function. Respiratory and forelimb motoneurons and neurochemical innervations of sympathetic preganglionic neurons were damaged following injury. This animal model can be used to evaluate the therapeutic efficacy of potential strategies to improve different physiological functions.

Spinal decompression surgery may alleviate vasopressor-induced spinal hemorrhage and extravasation during acute cervical spinal cord injury in rats

BACKGROUNDCervical spinal injury often disrupts the supraspinal vasomotor pathways projecting to the thoracic sympathetic preganglionic neurons, leading to cardiovascular dysfunction. The current guideline is to maintain the mean arterial blood pressure at 85 to 90 mmHg using a vasopressor during the first week of the injury. Some studies have demonstrated that this treatment might be beneficial to alleviate secondary injury and improve neurological outcomes; however, elevation of blood pressure may exacerbate spinal hemorrhage, extravasation, and edema, exacerbating the initial injury. PURPOSEThe present study was designed to (1) examine whether vasopressor administration exacerbates spinal hemorrhage and extravasation; (2) evaluate whether spinal decompression surgery relieves vasopressor-induced spinal hemorrhage and extravasation. STUDY DESIGNIn vivo animal study. METHODSAnimals received a saline solution or a vasopressor (phenylephrine hydrochloride, 500 or 1000 μg/kg, 7 mL/kg/h) after mid-cervical contusion with or without spinal decompression (ie, incision of the dura and arachnoid mater). Spinal cord hemorrhage and extravasation were examined by expression of Evans blue within the spinal cord section. RESULTSThe results demonstrated that cervical spinal contusion significantly reduced the mean arterial blood pressure and induced spinal hemorrhage and extravasation. Phenylephrine infusion significantly elevated the mean arterial blood pressure to the preinjury level within 15 to 60 minutes postcontusion; however, spinal hemorrhage and extravasation were more extensive in animals that received phenylephrine than in those that received saline. Notably, spinal decompression mitigated spinal hemorrhage and extravasation in contused rats who received phenylephrine. CONCLUSIONSThese data indicate that, although phenylephrine can prevent hypotension after cervical spinal injury, it also causes excess spinal hemorrhage and extravasation. CLINICAL SIGNIFICANCESpinal decompressive surgery seemed to minimize the side effect of phenylephrine as vasopressor treatment during acute spinal cord injury.

Transcriptome of rat subcortical white matter and spinal cord after spinal injury and cortical stimulation

Spinal cord injury disrupts ascending and descending neural signals causing sensory and motor dysfunction. Neuromodulation with electrical stimulation is used in both clinical and research settings to induce neural plasticity and improve functional recovery following spinal trauma. However, the mechanisms by which electrical stimulation affects recovery remain unclear. In this study we examined the effects of cortical electrical stimulation following injury on transcription at several levels of the central nervous system. We performed a unilateral, incomplete cervical spinal contusion injury in rats and delivered stimulation for one week to the contralesional motor cortex to activate the corticospinal tract and other pathways. RNA was purified from bilateral subcortical white matter and 3 levels of the spinal cord. Here we provide the complete data set in the hope that it will be useful for researchers studying electrical stimulation as a therapy to improve recovery from the deficits associated with spinal cord injury.

Impact of cervical spinal cord contusion on the breathing pattern across the sleep-wake cycle in the rat.

The present study was designed to investigate breathing patterns across the sleep-wake state following a high cervical spinal injury in rats. The breathing patterns (e.g., respiratory frequency, tidal volume, and minute ventilation), neck electromyogram, and electroencephalography of unanesthetized adult male rats were measured at the acute (i.e., 1 day), subchronic (i.e., 2 wk), and/or chronic (i.e., 6 wk) injured stages after unilateral contusion of the second cervical spinal cord. Cervical spinal cord injury caused a long-term reduction in the tidal volume but did not influence the sleep-wake cycle duration. The minute ventilation during sleep was usually lower than that during the wake period in uninjured animals due to a decrease in respiratory frequency. However, this sleep-induced reduction in respiratory frequency was not observed in contused animals at the acute injured stage. By contrast, the tidal volume was significantly lower during sleep in contused animals but not uninjured animals from the acute to the chronic injured stage. Moreover, the frequency of sigh and postsigh apnea was elevated in acutely contused animals. These results indicated that high cervical spinal contusion is associated with exacerbated sleep-induced attenuation of the tidal volume and higher occurrence of sleep apnea, which may be detrimental to respiratory functional recovery after cervical spinal cord injury. NEW & NOTEWORTHY Cervical spinal injury is usually associated with sleep-disordered breathing. The present study investigated breathing patterns across sleep-wake state following cervical spinal injury in the rat. Unilateral cervical spinal contusion significantly impacted sleep-induced alteration of breathing patterns, showing a blunted frequency response and exacerbated attenuated tidal volume and occurrence of sleep apnea. The result enables us to investigate effects of cervical spinal injury on the pathogenesis of sleep-disordered breathing and evaluate potential therapies to improve respiration.

Impact of cervical spinal contusion on the upper airway resistance in the rat

Bronchopulmonary C‐fiber induced pulmonary chemoreflex is a critical component of the respiratory defense reflex and characterized by cessation of inspiratory airflow (i.e., apnea) and increase of upper airway resistance (i.e., laryngeal closure). Our previous reports demonstrated that apneic response was attenuated following cervical spinal cord injury; however, it remained unclear whether the upper airway response of pulmonary chemoreflex was also influenced by spinal injury. Accordingly, the present study was designed to investigate the response of laryngeal function to bronchopulmonary C‐fiber activation following unilateral high‐cervical spinal cord contusion in rats. Adult Sprague–Dawley male rats were received laminectomy or unilateral contusion at C2 spinal cord using the MASCIS Impactor (height: 6.25 mm). The respiratory airflow and subglottal pressure in response to intra‐jugular capsaicin (1.5 μg/kg)‐induced pulmonary chemoreflex were measured under spontaneously breathing condition at 3 days, 2 weeks or 6 weeks following spinal surgery. The result demonstrated that high cervical contusion caused a long‐term reduction in the tidal volume without alteration of laryngeal resistance at three time points after injury. However, capsaicin‐induced increase of subglottal pressure was substantially attenuated in contused animals at 3 days post‐injury, and partially recovered at 2 and 6 weeks post‐injury. These results suggested that cervical spinal cord injury not only influence the breathing pattern but also impact the upper airway function. The attenuated laryngeal closure response may unfavorably reduce the ability to prevent inhaling irritants and cause the pulmonary pathological condition following cervical spinal cord injury.Support or Funding InformationMOST 105‐2628‐B‐110‐002‐MY3This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

XCT/Slc7a11 deletion accelerates motor recovery and improves histological outcomes following cervical spinal contusion in mice

xCT/Slc7a11 deletion accelerates motor recovery and improves histological outcomes following cervical spinal contusion in mice

Some Autonomic Deficits of Acute or Chronic Cervical Spinal Contusion Reversed by Interim Brainstem Stimulation.

Prolonged electrical stimulation of the hindbrain's nucleus raphe magnus (NRM) or of its major midbrain input region, the periaqueductal gray (PAG), was previously found in rats to promote recovery from sensory-motor and histological deficits of acute thoracic spinal cord injury (SCI). Here, some visceral deficits of acute and chronic midline cervical (C5) contusion are similarly examined. Cranially implanted wireless stimulators delivered intermittent 8 Hz, 30-70 μA cathodal pulse trains to a brainstem microelectrode. Injured controls were given inactive stimulators; rats without injuries or implants were also compared. Rectal distension or squeezing of the forepaws caused an exaggerated rise in mean arterial pressure in injured, untreated rats under anesthesia on post-injury week 6, probably reflecting autonomic dysreflexia (AD). These pressor responses became normal when 7 days of unilateral PAG stimulation was started on the injury day. Older untreated injuries (weeks 18-19) showed normal pressor responses, but unexpectedly had significant resting and nociceptive bradycardia, which was reversed by 3 weeks of PAG stimulation started on weeks 7 or 12. Subsequent chronic studies examined gastric emptying (GE), as indicated by intestinal transit of gavaged dye, and serum chemistry. GE and fasting serum insulin were reduced on injury weeks 14-15, and were both normalized by ∼5 weeks of PAG stimulation begun in weeks 7-8. Increases in calcitonin gene-related peptide, a prominent visceral afferent neurotransmitter, measured near untreated injuries (first thoracic segment) in superficial dorsal laminae were reversed by acutely or chronically initiated PAG stimulation. The NRM, given 2-3 weeks of stimulation beginning 2 days after SCI, prevented abnormalities in both pressor responses and GE on post-injury week 9, consistent with its relaying of repair commands from the PAG. The descending PAG-NRM axis thus exhibits broadly restorative influences on visceral as well as sensory-motor deficits, improving chronic as well as acute signs of injury.

Mild Acute Intermittent Hypoxia Improves Respiratory Function in Unanesthetized Rats With Midcervical Contusion

Background. Mild intermittent hypoxia has been considered a potential approach to induce respiratory neuroplasticity. Objective. The purpose of the present study was to investigate whether mild acute intermittent hypoxia can improve breathing function in a clinically relevant spinal cord injury animal model. Methods. Adult male rats received laminectomy or unilateral contusion at the C3-C4 spinal cord using a MASCIS Impactor (height: 6.25 or 12.5 mm). At 4 weeks postinjury, the breathing patterns of unanesthetized rats were measured by whole body plethysmography before, during and after 10 episodes of 5 minutes of hypoxia (10% O2, 4% CO2, balance N2) with 5 minutes of normoxia intervals. Results. The results demonstrated that cervical contusion resulted in reduction in breathing capacity and number of phrenic motoneurons. Acute hypoxia induced significant increases in frequency and tidal volume in sham surgery and contused animals. In addition, there was a progressive decline in the magnitude of hypoxic ventilatory response during intermittent hypoxia. Further, the tidal volume was significantly enhanced in contused but not sham surgery rats at 15 and 30 minutes postintermittent hypoxia, suggesting intermittent hypoxia can bring about long-term facilitation of tidal volume following cervical spinal contusion. Conclusions. These results suggest that mild acute intermittent hypoxia can elicit differential forms of respiratory plasticity in sham surgery versus contused animals, and may be a promising neurorehabilitation approach to improve respiratory function after cervical spinal cord injury.

Cervical Spinal Contusion Alters NKCC1 and KCC2 Expression in Phrenic Motor Neurons

Spinal chloride‐dependent synaptic inhibition plays a key role in coordinating breathing. Chloride‐dependent synaptic inhibition requires neuronal chloride gradients established by the balance of the membrane‐bound chloride co‐transporters NKCC1 and KCC2. Spinal transection disrupts the NKCC1/KCC2 balance, diminishing chloride gradients in neurons below the injury, potentially contributing to the spasticity in many spinal injury patients. It is not known if similar disruptions in the NKCC1/KCC2 balance occur in respiratory motor neurons below incomplete cervical contusion injuries. Such disruptions could have dual effects, partially reversing respiratory muscle paralysis, but with the disadvantage of dis‐coordination/spasticity in respiratory muscles. Here, we tested the hypothesis that incomplete, cervical spinal contusion injuries disrupt NKCC1/KCC2 regulation in identified phrenic motor neurons. Further, since some of the same kinases regulating NKCC1 and KCC2 membrane trafficking and gene expression are activated by acute intermittent hypoxia (AIH), we tested the hypothesis that repetitive AIH normalizes membrane NKCC1 and KCC2 expression in phrenic motor neurons after cervical contusion injuries. One week after unilateral C2 contusions (135KD; Infinite Horizons) or sham surgeries, rats were exposed to either normoxia or repetitive AIH (10, 5 min episodes per day, 5 min intervals; 3 days per week) for 4 weeks. All rats received intrapleural injections of Cholera toxin B fragment (CTB) to identify phrenic motor neurons. Immunofluorescence and confocal microscopy were used to reveal NKCC1 and KCC2 protein within CTB‐positive phrenic motor neurons; NKCC1 and KCC2 immuoreactivity in phrenic motor neurons was assessed with a semi‐automated quantification algorithm implemented in MATLAB. First, CTB‐positive phrenic motor neuron somata were identified. Then, optical density was assessed in the cytosol and the presumptive phrenic motor neuron membrane. After unilateral C2 contusions: 1) NKCC1 level at the cell membrane relative to the cytosol increased after cervical spinal contusion both ipsi‐ and contralateral to the injury; and 2) KCC2 levels at the cell membrane relative to the cytosol marginally decreased contralateral to injury (p = 0.07) mainly due to increased cytosolic KCC2 expression on both sides. Repetitive AIH had no significant effects on either protein versus normoxic controls. Thus, unilateral C2 contusion injury exerts complex effects on the NKCC1/KCC2 balance in phrenic motor neurons five weeks post‐injury. These changes may enable at least partial compensation for loss of inspiratory drive to phrenic motor neurons since diminished chloride gradients should increase motor neuron excitability and preserve tidal volume. However, compensation may come at the cost of respiratory muscle coordination, such as sporadic diaphragm activation during expiration. Increased cytosolic KCC2 and decreased cytosolic NKCC1 expression suggest that regulatory mechanisms are working to restore a normal NKCC1/KCC2 balance at this time post‐injury.Support or Funding InformationDoD CDMRP SC120226 and NIH HL69064

Acute theophylline exposure modulates breathing activity through a cervical contusion

Cervical spinal contusion injuries are the most common form of spinal cord injury (>50%) observed in humans. These injuries can result in the impaired ability to breathe. In this study we examine the role of theophylline in the rescue of breathing behavior after a cervical spinal contusion. Previous research in the C2 hemisection model has shown that acute administration of theophylline can rescue phrenic nerve activity and diaphragmatic EMG on the side ipsilateral to injury. However, this effect is dependent on intact and uninjured pathways. In this study we utilized a cervical contusion injury model that more closely mimics the human condition. This injury model can determine the effectiveness of therapeutic interventions, in this case theophylline, on the isolated contused pathways of the spinal cord. Three weeks after a 150kD C3/4 unilateral contusion subjects received a 15mg/kg dose of theophylline prior to a contralateral C2 hemisection. Subjects that received theophylline were able to effectively utilize damaged pathways to breathe for up to 2min, while subjects treated with saline were unable to support ventilation. Through these experiments, we demonstrate that theophylline can make injured pathways that mediate breathing more effective and therefore, suggest a potential therapeutic role in the critical time points immediately after injury.

Time course of respiratory dysfunction and phrenic motor neuron death following cervical spinal contusion in rats

Event Abstract Back to Event Time course of respiratory dysfunction and phrenic motor neuron death following cervical spinal contusion in rats Charles Nicaise1*, Roland Pochet1 and Angelo Lepore2 1 Universite Libre de Bruxelles, Laboratoire d'histologie, de neuroanatomie et de neuropathologie, Belgium 2 Thomas Jefferson University, Department of Neuroscience, United States Respiratory dysfunction is the leading cause of morbidity and mortality following traumatic spinal cord injury (SCI). Injuries targeting mid-cervical (C3-C5) spinal cord regions affect the phrenic nucleus that innervates the diaphragm, the primary respiratory muscle of inspiration. Contusion-type injury in the cervical spinal cord is one of the most common forms of human SCI; however, few studies have evaluated mid-cervical contusion in animal models or characterized consequent histopathological and functional effects of degeneration of phrenic motor neuron–diaphragm circuitry. In an attempt to characterize the time course of phrenic motor neuron death and respiratory dysfunction, we sought to create a unilateral contusion injury in rats and followed the animals for two weeks. Our injury paradigm leads to rapid but transient changes of respiratory parameters such as the breathing frequency, minute volume or inspiratory/expiratory times, measured by whole-body plethysmography. It is accompanied by phrenic motor neuron loss, phrenic nerve degeneration, denervation at the diaphragm neuromuscular junction, changes in spontaneous diaphragm EMG recordings and reduction of phrenic nerve compound muscle action potential amplitude. These findings demonstrate significant and persistent respiratory compromise following mid-cervical SCI. These injury paradigms provide important tools both for understanding mechanisms of phrenic motor neuron and diaphragm pathology following SCI and for evaluating the therapeutic window in clinically relevant cervical SCI models. Keywords: Cervical, Diaphragm, phrenic motor neuron, respiratory function, spinal cord injury Conference: Belgian Brain Council, Liège, Belgium, 27 Oct - 27 Oct, 2012. Presentation Type: Poster Presentation Topic: Higher Brain Functions in health and disease: cognition and memory Citation: Nicaise C, Pochet R and Lepore A (2012). Time course of respiratory dysfunction and phrenic motor neuron death following cervical spinal contusion in rats. Conference Abstract: Belgian Brain Council. doi: 10.3389/conf.fnhum.2012.210.00136 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Apr 2012; Published Online: 12 Sep 2012. * Correspondence: Dr. Charles Nicaise, Universite Libre de Bruxelles, Laboratoire d'histologie, de neuroanatomie et de neuropathologie, Bruxelles, 1070, Belgium, charles.nicaise@unamur.be Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Charles Nicaise Roland Pochet Angelo Lepore Google Charles Nicaise Roland Pochet Angelo Lepore Google Scholar Charles Nicaise Roland Pochet Angelo Lepore PubMed Charles Nicaise Roland Pochet Angelo Lepore Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Breathing patterns after mid-cervical spinal contusion in rats

Respiratory failure is the leading cause of death after cervical spinal injury. We hypothesized that incomplete cervical spinal injuries would alter respiratory pattern and initiate plasticity in the neural control of breathing. Further, we hypothesized that the severity of cervical spinal contusion would correlate with changes in breathing pattern. Fourteen days after C4–C5 contusions, respiratory frequency and tidal volume were measured in unanesthetized Sprague Dawley rats in a whole body plethysmograph. Phrenic motor output was monitored in the same rats which were anesthetized, vagotomized, paralyzed and ventilated to eliminate and/or control sensory feedback that could alter breathing patterns. The extent of spinal injury was approximated histologically by measurements of the injury-induced cyst area in transverse sections; cysts ranged from 2 to 28% of spinal cross-sectional area, and had a unilateral bias. In unanesthetized rats, the severity of spinal injury correlated negatively with tidal volume (R 2 = 0.85; p < 0.001) and positively with breathing frequency (R 2 = 0.65; p < 0.05). Thus, the severity of C4–C5 spinal contusion dictates post-injury breathing pattern. In anesthetized rats, phrenic burst amplitude was decreased on the side of injury, and burst frequency correlated negatively with contusion size (R 2 = 0.51; p < 0.05). A strong correlation between unanesthetized breathing pattern and the pattern of phrenic bursts in anesthetized, vagotomized and ventilated rats suggests that changes in respiratory motor output after spinal injury reflect, at least in part, intrinsic neural mechanisms of CNS plasticity initiated by injury.

PEGylated interferon-β modulates the acute inflammatory response and recovery when combined with forced exercise following cervical spinal contusion injury

Secondary degeneration leads to an expansion of the initial tissue damage sustained during a spinal cord injury (SCI). Dampening the cellular inflammatory response that contributes to this progressive tissue damage is one possible strategy for neuroprotection after acute SCI. We initially examined whether treatment with a PEGylated form of rat interferon-beta (IFN-β) would modulate the expression of several markers of inflammation and neuroprotection at the site of a unilateral cervical level 5 contusion injury. Adult female Sprague–Dawley rats were injured using the Infinite Horizon Impactor at a force of 200 kdyn (equivalent to a severe injury) and a mean displacement of 1600–1800 μm. A single dose (5 × 10 6 units) of PEGylated IFN-β or vehicle was administered 30 min following SCI. Here we demonstrate temporal changes in pro- and anti-inflammatory cytokine levels and the expression of heat shock proteins and iNOS (involved in neuroprotection) at the lesion epicenter and one segment caudally after SCI and PEG IFN-β treatment. The results suggested a potential therapeutic treatment strategy for modulation of secondary damage after acute SCI. Therefore, we examined whether acute treatment with PEG IFN-β would improve forelimb function alone or when combined with forced exercise (Ex). Animals began the Ex paradigm 5 days post SCI and continued for 5 days/week over 8 weeks. Locomotion (forelimb locomotor scale [FLS], hindlimb BBB, and TreadScan) and sensorimotor function (grid walking) was tested weekly. Additional outcome measures included lesion size and glial cell reactivity. Significant FLS improvements occurred at 1 week post SCI in the PEGylated IFN-β-treated group but not at any other time point or with any other treatment approaches. These results suggest that this acute neuroprotective treatment strategy does not translate into long term behavioral recovery even when combined with forced exercise.

Aspiration of a cervical spinal contusion injury in preparation for delayed peripheral nerve grafting does not impair forelimb behavior or axon regeneration

A peripheral nerve graft model was used to examine axonal growth after a unilateral cervical (C) contusion injury in adult rats and to determine if manipulation of an injury site prior to transplantation affects spontaneous behavioral recovery. After a short delay (7 d) the epicenter of a C4 contusion was exposed and aspirated without harming the cavity walls followed by apposition with one end of a pre-degenerated tibial nerve to the rostral cavity wall. After a longer delay (28 d) the aspirated cavity was treated with GDNF to promote regeneration by chronically injured neurons. In both groups forelimb and hindlimb locomotor scores decreased significantly 2 d after lesion site manipulation, but by 7 d, the forelimb score was not different from the pre-manipulation score. There was no significant difference in grid walking or grip strength scores for the affected forelimb in either group 7 d after contusion vs. 7 d after manipulation. Over 1500 brain stem and propriospinal neurons grew axons into the graft with either delay. These results demonstrate that a contusion injury site can be manipulated prior to transplantation without causing long-lasting forelimb or hindlimb behavioral deficits and that peripheral nerve grafts support axonal growth after acute or chronic contusion injury.

A new model of upper cervical spinal contusion inducing a persistent unilateral diaphragmatic deficit in the adult rat

Research on spinal cord trauma requires models reflecting the contusion mechanisms encountered in clinical situation. The aim of this study was to develop in the adult rat a reproducible model of upper cervical spinal cord contusion inducing persistent unilateral diaphragm deficit. After dura and pia matter removal, weight drop and compression were targeted at the ventro-lateral funiculi which contain the bulbospinal descending respiratory pathways that command the phrenic motoneurons innervating the diaphragm. At 7 days post-injury, the left diaphragm activity recorded in contused rats (27.4 +/- 5.1% of the contralateral activity) was significantly lower than in the sham group (97.6 +/- 1.2%). This respiratory deficit still persisted 1 month later. Histology showed a reproducible left C2-lateralized lesion that involved both white and gray matter including the ventro-lateral funiculi. This C2 contusion model provides a basis for testing both regenerative and neuroprotective strategies aimed at improving functional respiratory recovery after spinal cord trauma.