The current investigation aimed to establish a respiration-triggered trans-spinal magnetic stimulation configuration and examine its modulatory effect on bilateral diaphragmatic motor-evoked potentials following cervical spinal cord injury. Diaphragmatic motor-evoked potential responses were assessed during inspiration- and expiration-triggered trans-spinal magnetic stimulation under different respiratory drives (i.e., normocapnia and hypercapnia) in both spinal-intact and cervical spinal cord contused rats. The results demonstrated that inspiration-triggered trans-spinal magnetic stimulation elicited a greater bilateral diaphragmatic motor-evoked potential response compared with expiration-triggered trans-spinal magnetic stimulation in uninjured animals. Moreover, heightened respiratory drives induced by hypercapnia diminished the bilateral diaphragmatic motor-evoked potential response during respiration-triggered trans-spinal magnetic stimulation. Notably, high-intensity inspiration-triggered trans-spinal magnetic stimulation mitigated diaphragmatic bursting that occurred after motor-evoked potentials (i.e., post-motor-evoked potential activity). Cervical spinal cord contusion not only reduced inspiratory diaphragmatic activity but also influenced trans-spinal magnetic stimulation-induced diaphragmatic motor-evoked potentials. Specifically, the respiratory modulatory effect of trans-spinal magnetic stimulation on diaphragmatic motor-evoked potentials was blunted in the diaphragm ipsilateral to the lesion. Additionally, the inhibitory impact of inspiration-triggered trans-spinal magnetic stimulation on post-motor-evoked potential activity was also attenuated in contused animals. These results suggest that the effect of trans-spinal magnetic stimulation on diaphragmatic motor-evoked potentials is modulated by respiratory phases and drives. Respiration-triggered trans-spinal magnetic stimulation may serve as a tool to evaluate changes in diaphragm excitability and spinal respiratory circuits following cervical spinal cord injury.

Traumatic cervical spinal cord injury (cSCI) causes severe neurological deficits and long-term disability. Preclinical models such as cervical vertebrate level 2 (C2) hemisection (C2HS), which disrupts communication between respiratory centers and the phrenic motoneurons pool, have been used for decades to study respiratory dysfunction and neuroinflammation after cSCI. Recently, contusive injuries such as cervical vertebrate level 3 hemicontusion (C3HC) have been increasingly employed, as they induce phrenic motoneuron damage and offer a more clinically relevant model of SCI. However, these two different models may engage distinct pathophysiological cascades, raising concerns about the generalizability of findings across injury paradigms. In this study, we compared neuroimmune responses following C2HS or C3HC in mice. Animals underwent either lesion, and spinal cord segments (C1-C8) were collected seven days post-injury for immuno-histological analyses around the lesion level and flow cytometry analyses at the lesion level. We observed that C2HS preserved more neurons accompanied by an upregulation of CD86 and F4/80 in macroglia, markers of activated macrophages, suggesting a response oriented toward phagocytic and reparative functions. This phenotype was associated with limited pro-inflammatory cell infiltration and normalized level of systemic IL-6 level. Conversely, C3HC induced more extensive tissue damage, heightened microglial activation, a trend toward increased astrocytic reactivity, and significantly elevated CSPG levels on the contralateral side. Moreover, a persistent NK cell, neutrophil, and CD43+ infiltrating cells, along with sustained elevation of circulating IL-6 These findings demonstrate distinct neuroinflammatory signatures and repairing mechanisms between models. This study underscores, for the first time, how injury type shapes neuroimmune mechanisms, reinforcing the need for lesion-specific therapeutic strategies in cervical spinal cord injury.

IntroductionExcessive activation of the adenosine A2A receptor (A2AR) contributes to chronic neuroinflammation, in part through spatial coupling with the adenosine-generating enzyme CD73, which enables localized adenosine signaling. Coordinated regulation of Nt5e and Adora2a across neuropathological conditions supports dual targeting of the CD73/A2AR axis to constrain maladaptive inflammatory signaling.MethodsPrimary rat astrocytes were exposed to TNF-α, IL-1α, and C1q (TIC) to induce a neurotoxic reactive astrocyte (nRA) substate. Concomitant pharmacological inhibition of CD73 (APCP, 100 μM) and A2AR (istradefylline, 10 μM) was applied. Morphological, redox, inflammatory, and functional outcomes were assessed, including CD73 expression and activity, CD73/A2AR spatial proximity, cytokine release, and astrocyte-mediated neurotoxicity.ResultsDual CD73/A2AR blockade attenuated key features of the nRA phenotype, including astrocyte hypertrophy, oxidative stress, and impaired antioxidant capacity. These effects were associated with normalization of CD73 expression and activity, reduced spatial proximity between CD73 and A2AR, suppression of IL-1β release and complement- and immune cell-recruiting effector programs (C3, VCAM1), and modulation of redox-sensitive pathways (Nos2/NO, NRF2). Notably, IL-6- and TNFα-driven core inflammatory signaling remained preserved. Functionally, dual blockade shifted astrocytes toward a less neurotoxic phenotype, reducing their impact on neuronal Ca2+ homeostasis and improving neuronal viability.DiscussionThese findings demonstrate that dual CD73/A2AR blockade selectively reconfigures astrocyte inflammatory networks under the tested conditions, without broadly suppressing inflammatory or homeostatic functions at the examined time point. This supports the CD73/A2AR axis as a promising therapeutic target for limiting chronic astrocyte-driven neurotoxicity.

Abstract Cervical spinal cord injury (SCI) frequently leads to life-threatening respiratory insufficiency by disrupting descending phrenic pathways. There is growing interest in non-invasive neuromodulatory approaches to enhance plasticity of spared respiratory circuits. We investigated whether cervical repetitive magnetic stimulation (rMS) applied to the injured cervical spinal cord promotes ventilatory recovery in a preclinical mouse model. Adult mice received a unilateral C3 hemicontusion followed by either rMS or sham stimulation. We found that rMS-treated mice significantly improved recovery of tidal volume and minute ventilation at 21 days post injury(dpi) compared to sham controls under various breathing conditions (isoflurane anesthesia, poikilocapnic phase and hypercapnic challenge). Correspondingly, diaphragm EMG enhanced ipsilateral hemidiaphragm activity in ventral and medial regions, and even contralateral hemidiaphragm activity in its ventral part. This was associated with a marked attenuation of the inflammatory response at the cervical spinal cord level. Indeed, rMS lowered astroglial, fibrotic scarring, pro-inflammatory CD68-, Iba1- microglial/macrophage markers. Moreover, perineuronal net expression (WFA positive staining) is globally reduced in the ventral spinal horn, whereas at the lesion site it is markedly increased and tightly wrapped around motoneurons. Together, these findings demonstrate that rMS promotes functional respiratory recovery after cervical SCI through combined enhancement of diaphragmatic motor output and modulation of the inflammatory and extracellular environment. Together, these functional and cellular findings indicate that spinal rMS promotes a permissive, pro-regenerative environment supporting respiratory circuit plasticity. We conclude that rMS significantly enhances ventilatory recovery via reduced inflammatory response and improved intraspinal rewiring after high cervical SCI, suggesting it is a promising non-invasive strategy. The ability of rMS to engage spared respiratory networks and support neuroplasticity highlights its promise as a safe, non-invasive therapeutic strategy with translational potential for rehabilitation of breathing function after SCI. One Sentence Summary Noninvasive cervical magnetic stimulation improves breathing after spinal cord injury by boosting diaphragm activity and reducing inflammation.

Sepsis is a potentially life-threatening condition recognized as a global health priority by the World Health Organization. Survivors who develop intensive care unit-acquired weakness (ICUAW) often face long-term motor and functional deficits that significantly impact their quality of life. Although some studies have investigated the mechanisms underlying ICUAW and its long-term effects, much remains unknown. Further research into ICUAW is therefore essential to gain a comprehensive understanding of this phenomenon, which may guide the development of effective treatments to restore patients' quality of life.

High spinal cord injuries (SCIs) often result in persistent diaphragm paralysis and respiratory dysfunction. Chronic neuroinflammation within the damaged spinal cord after injury plays a prominent role in limiting functional recovery by impeding neuroplasticity. In this study, we aimed to reduce glucose metabolism that supports neuroinflammatory processes in an acute preclinical model of C2 spinal cord lateral hemisection in rats. We administered 2-deoxy-D-glucose (2-DG; 200mg/kg/day s.c., for 7 days) and evaluated the effect on respiratory function and chondroitin sulfate proteoglycans (CSPGs) production around spinal phrenic motoneurons. Contrary to our initial hypothesis, our 2-DG treatment did not have any effect on diaphragm activity and CSPGs production in injured rats, although slight increases in tidal volume were observed. Unexpectedly, it led to deleterious effects in uninjured (sham) animals, characterized by increased ventilation and CSPGs production. Ultimately, our results seem to indicate that this 2-DG treatment paradigm may create a neuroinflammatory state in healthy animals, without affecting the already established spinal inflammation in injured rats.

Abstract Sepsis via innate immune system activation causes organ dysfunction. Among these, the central nervous system (CNS) is particularly affected by sepsis-associated encephalopathies. These symptoms are linked with the activation of microglia and leukocyte infiltration. These immune cells have been discovered to have the ability to produce extracellular traps (ETs). While these components capture and destroy pathogens, deleterious effects occur such as reduced neuronal excitability with excessive production. In this study, the objectives were to determine whether (1) immune cells form ETs in the CNS by using two models of sepsis: lipopolysaccharide (LPS) and cecal ligation and puncture (CLP); (2) ETs produce neuromuscular disorders, and (3) a threshold is necessary to produce these disorders. Our results demonstrate a systemic inflammation for both models. As expected, the LPS administration increases leukocyte infiltration into the CNS, activates immune cells and produces ETs, which directly impair the gastrocnemius motoneuron excitability. Sivelastat, an inhibitor of ET formation significantly decreases the production of ETs in immune cells and induces a preservation of the neuromuscular function without decrease of the inflammatory response. This infiltration of leukocytes and production of ETs is also observed using the CLP model, at a lower stage, without neuromuscular dysfunctions, suggesting that the CNS has an ET threshold in order to display these deleterious effects.

Abstract High spinal cord injuries (SCIs) lead to persistent diaphragm paralysis and related respiratory dysfunctions. The absence of functional recovery is due to limited neuroplasticity processes, mainly caused by chronic neuroinflammation occurring in the injured spinal cord. In this study, we aimed at reducing glucose metabolism that supports neuroinflammatory processes in an acute preclinical model of C2 spinal cord lateral hemi-section in rats. We administered 2-Deoxy-D-glucose (2-DG; 200 mg/kg/day s.c. for 7 days) and evaluated the effect on respiratory function and chondroitin sulfate proteoglycans (CSPGs) production around spinal phrenic motoneurons. Contrary to our initial hypothesis, our 2-DG treatment did not have any effect on diaphragm activity and CSPGs production in injured rats, even if a slight increase in tidal volume can be observed. Unexpectedly, it led to deleterious effects in uninjured (sham) animals, characterized by an increased ventilation and CSPGs production. Globally, our results seem to indicate that this 2-DG treatment paradigm could create a neuroinflammatory state in healthy animals, without altering or modulating the already installed spinal inflammation in injured rats. Given the established beneficial effects of 2-DG observed in other studies on neuronal activity and inflammation, adapted2-DG doses and/or longer treatment duration should be explored for reducing deleterious inflammatory processes occurring after SCI.

Abstract The present study was designed to examine the effect of trans‐spinal magnetic stimulation on bilateral respiratory and forelimb muscles in healthy subjects. Two wings of a figure‐of‐eight magnetic coil were placed on the dorsal vertebrae, from the fifth cervical to the second thoracic dorsal vertebra with a center at the seventh cervical vertebra. The surface electromyograms of bilateral diaphragm and biceps were recorded in response to trans‐spinal magnetic stimulation with 20%–100% maximum output of the stimulatory device in male (n = 12) and female participants (n = 8). Trans‐spinal magnetic stimulation can induce a co‐activation of bilateral diaphragm and biceps when the stimulation intensity is above 60%. The onset latency was comparable between the left and right sides of the muscles, suggesting bilateral muscles could be simultaneously activated by trans‐spinal magnetic stimulation. In addition, the intensity–response curve of the biceps was shifted upward compared with that of the diaphragm in males, indicating that the responsiveness of the biceps was greater than that of the diaphragm. This study demonstrated the feasibility of utilizing trans‐spinal magnetic stimulation to co‐activate the bilateral diaphragm and biceps. We proposed that this stimulatory configuration can be an efficient approach to activate both respiratory and forelimb muscles.

Sepsis is one of the leading causes of death worldwide, and no therapy is available other than intensive care treatments. Drug development attempts have mainly focused on controlling inflammation or treating dysfunction, without significant improvement in the last decades. Recently, interest has emerged in β1-adrenergic blockade, which has proved beneficial to both parameters. Unfortunately, the specific underlying mechanisms have not been addressed yet. Our study aimed to investigate on mice (adult Swiss male, 30-45g) lipopolyssacharide or cecal ligature and puncture models the effects of atenolol, a β1-adrenergic blocker, currently used in intensive care units for hypertension and arrhythmia. The results demonstrated a beneficial effect of treatment on survival and a preservation of cardiac function including left ventricular ejection fraction (33±2,8% in sepsis group versus 55±5,1% in sepsis-treated group, p<0,05) at a concentration reducing heart rate by approximately 10%.We wondered if beneficial results obtained with atenolol could be due to a modulation of extracellular traps. These components are essential in pathogen spreading control and are increased during sepsis. However, an excess of their production induces vascular occlusions and acute heart injuries.We demonstrated that neutrophils extracellular traps were increased in heart and blood during sepsis and decreased significantly following atenolol administration (blood: 1.1±0,3% in control group, 13,4±1.8% in sepsis group, 6.9±1.2% in sepsis-treated group). This beneficial effect of atenolol was not associated with other modulations of neutrophil function such as their ability to phagocyte (33,6±3,9% in sepsis group versus 25.6±3.6% in sepsis-treated group, p>0,05), to undergo apoptosis (Annexin V+/ L/D-: 13,2±2.1% in sepsis group versus 14.1±2.9% in sepsis-treated group, p>0,05) or to degranulate. Blood neutrophil phenotypes associated with their maturation state (expression of CD62L and CXCR2) or ability to migrate into tissue (expression of adhesion molecules PSGL1, LFA1, VLA4, PECAM1) was also similar between LPS and LPS-treated groups. Although, the modulation of extracellular traps production by atenolol was also observed in other immune cells population able to extrude chromatin fibers in extracellular space such as macrophages. These results suggest a specific beneficial effect of ß1-adrenergic blockers on extracellular traps formation associated with cardiac function preservation and ultimately survival without detrimental effect on heart rate during widespread inflammation. This work was supported by funding from INSERM and Paris-Saclay University-UVSQ. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Peripheral nerve injuries induce long-lasting physiological and severe functional impairment due to motor, sensory, and autonomic denervation. Preclinical models allow us to study the process of nerve damage, evaluate the capacity of the peripheral nervous system for spontaneous recovery, and test diagnostic tools to assess the damage and subsequent recovery. Methods: In this study on Sprague–Dawley rats, we: (1) compared the use of two different anesthetics (isoflurane and urethane) for the evaluation of motor evoked potentials (MEPs) induced by trans-spinal magnetic stimulation (TSMS) in gastrocnemius and brachioradialis muscles; (2) monitored the evolution of gastrocnemius MEPs by applying paired-pulse stimulation to evaluate the neuromuscular junction activity; and (3) evaluated the MEP amplitude before and after left tibialis nerve crush (up to 7 days post-injury under isoflurane anesthesia). The results showed that muscle MEPs had higher amplitudes under isoflurane anesthesia, as compared with urethane anesthesia in the rats, demonstrating higher motoneuronal excitability under isoflurane anesthesia evaluated by TSMS. Following tibial nerve crush, a significant reduction in gastrocnemius MEP amplitude was observed on the injured side, mainly due to axonal damage from the initial crush. No spontaneous recovery of MEP amplitude in gastrocnemius muscles was observed up to 7 days post-crush; even a nerve section did not induce any variation in residual MEP amplitude, suggesting that the initial crush effectively severed the axonal fibers. These observations were confirmed histologically by a drastic reduction in the remaining myelinated fibers in the crushed tibial nerve. These data demonstrate that TSMS can be reliably used to noninvasively evaluate peripheral nerve function in rats. This method could therefore readily be applied to evaluate nerve conductance in the clinical environment.

Hypotheses: Moderate acute intermittent hypoxia (mAIH) elicits plasticity in both respiratory (phrenic long-term facilitation; pLTF) and sympathetic nerve activity (sympLTF) in rats. Although mAIH produces pLTF in normal rats, inconsistent results are reported after cervical spinal cord injury (cSCI), possibly due to greater spinal tissue hypoxia below the injury site. There are no reports concerning cSCI effects on sympLTF. Since mAIH is being explored as a therapeutic modality to restore respiratory and non-respiratory movements in humans with chronic SCI, both effects are important. To understand cSCI effects on mAIH-induced pLTF and sympLTF, partial or complete C2 spinal hemisections (C2Hx) were performed and, 2 weeks later, we assessed: 1) ipsilateral cervical spinal tissue oxygen tension; 2) ipsilateral & contralateral pLTF; and 3) ipsilateral sympLTF in splanchnic and renal sympathetic nerves.Methods: Male Sprague-Dawley rats were studied intact, or after partial (single slice) or complete C2Hx (slice with-1 mm aspiration). Two weeks post-C2Hx, rats were anesthetized and prepared for recordings of bilateral phrenic nerve activity and spinal tissue oxygen pressure (PtO2). Splanchnic and renal sympathetic nerve activity was recorded in intact and complete C2Hx rats.Results: Spinal PtO2 near phrenic motor neurons was decreased after C2Hx, an effect most prominent with complete vs. partial injuries; baseline PtO2 was positively correlated with mean arterial pressure. Complete C2Hx impaired ipsilateral but not contralateral pLTF; with partial C2Hx, ipsilateral pLTF was unaffected. In intact rats, mAIH elicited splanchnic and renal sympLTF. Complete C2Hx had minimal impact on baseline ipsilateral splanchnic or renal sympathetic nerve activity and renal, but not splanchnic, sympLTF remained intact.Conclusion: Greater tissue hypoxia likely impairs pLTF and splanchnic sympLTF post-C2Hx, although renal sympLTF remains intact. Increased sympathetic nerve activity post-mAIH may have therapeutic benefits in individuals living with chronic SCI since anticipated elevations in systemic blood pressure may mitigate hypotension characteristic of people living with SCI.

High spinal cord injuries (SCIs) lead to permanent functional deficits, including respiratory dysfunction. Patients living with such conditions often rely on ventilatory assistance to survive, and even those that can be weaned continue to suffer life-threatening impairments. There is currently no treatment for SCI that is capable of providing complete recovery of diaphragm activity and respiratory function. The diaphragm is the main inspiratory muscle, and its activity is controlled by phrenic motoneurons (phMNs) located in the cervical (C3–C5) spinal cord. Preserving and/or restoring phMN activity following a high SCI is essential for achieving voluntary control of breathing. In this review, we will highlight (1) the current knowledge of inflammatory and spontaneous pro-regenerative processes occurring after SCI, (2) key therapeutics developed to date, and (3) how these can be harnessed to drive respiratory recovery following SCIs. These therapeutic approaches are typically first developed and tested in relevant preclinical models, with some of them having been translated into clinical studies. A better understanding of inflammatory and pro-regenerative processes, as well as how they can be therapeutically manipulated, will be the key to achieving optimal functional recovery following SCIs.

Sepsis is characterized by a dysregulated host response to an infection, potentially leading to fatal organ dysfunctions. Among these organs, the central nervous system (CNS) is particularly affected with encephalopathies associated or not with chronic disabling pain. These symptoms are caused by broad neuroinflammation with activation of resident microglia cells and infiltration of leukocytes, especially neutrophils. These immune cells have the ability to produce extracellular traps (ETs) in blood and tissues. These components are composed of chromatins and various antimicrobial proteins, and its role is to capture and destroy pathogens. However, in case of excessive production, deleterious effects occur such as tissue damage and reduction of neuronal excitability.In this study, the objectives were: 1) to determine whether in a model of endotoxemic shock, neutrophils and microglia form ETs in the CNS; 2) and to determine if a modulation of ETs production was beneficial on neuromuscular disorders associated with endotoxemic shock.We observed an infiltration of neutrophils in the SNC, an activation of microglia and a production of ETs following intraperitoneal lipopolyssacharide (LPS) administration in mice (adult Swiss male, 30-45g). Atenolol, a β1-adrenergic blocker with intrinsic immunomodulatory properties, significantly decreases the production of ETs associated in both microglia and neutrophils (citrullinated histone H3: 279.1 ± 101.9 MFI versus 117.1 ± 77.21 MFI, p<0,01). In addition, this treatment preserved the gastrocnemius motoneurons excitability (39,93 ± 15,16 mV in control group, 8.147 ± 5.892 mV in LPS group and 27.32 ± 10.73 mV in LPS+atenolol group). Similar results have been observed when the production of ETs was prevented by using sivelestat (inhibitor of extracellular traps).In conclusion, our results demonstrate that sepsis increases neutrophil infiltration into the spinal cord, activates immune cells and produces extracellular traps that directly impair motor function. Prevention of ETs formation partly restores motor function and could be a good target in order to reduce adverse effects in sepsis but also in other motor related pathologies. This work was supported by funding from the Chancellerie des Universites de Paris (Legs Poix), INSERM and Paris-Saclay University-UVSQ. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Severe inflammation via innate immune system activation causes organ dysfunction. Among these, the central nervous system (CNS) is particularly affected by encephalopathies. These symptoms are associated with the activation of microglia and a potential infiltration of leukocytes. These immune cells have recently been discovered to have the ability to produce extracellular traps (ETs). While these components capture and destroy pathogens, deleterious effects occur such as reduced neuronal excitability correlated with excessive ETs production. In this study, the objectives were to determine (1) whether immune cells form ETs in the CNS during acute inflammation (2) whether ETs produce neuromuscular disorders and (3) whether an immunomodulatory treatment such as β1-adrenergic blockers limits these effects. We observed an infiltration of neutrophils in the CNS, an activation of microglia and a production of ETs following lipopolysaccharide (LPS) administration. Atenolol, a β1-adrenergic blocker, significantly decreased the production of ETs in both microglia and neutrophils. This treatment also preserved the gastrocnemius motoneuron excitability. Similar results were observed when the production of ETs was prevented by sivelestat, an inhibitor of ET formation. In conclusion, our results demonstrate that LPS administration increases neutrophils infiltration into the CNS, activates immune cells and produces ETs that directly impair neuromuscular function. Prevention of ETs formation by β1-adrenergic blockers partly restores this function and could be a good target in order to reduce adverse effects in severe inflammation such as sepsis but also in other motor related pathologies linked to ETs production.

BACKGROUND CONTEXT:Magnetic stimulation can noninvasively modulate the neuronal excitability through different stimulatory patterns. PURPOSE:The present study hypothesized that trans-spinal magnetic stimulation with intermittent theta burst stimulatory pattern can modulate respiratory motor outputs in a pre-clinical rat model of cervical spinal cord injury. STUDY DESIGN:In vivo animal study. METHODS:The effect of trans-spinal magnetic intermittent theta burst stimulation on diaphragmatic activity was assessed in adult rats with unilateral cervical spinal cord contusion at 2 weeks postinjury. RESULTS:The results demonstrated that unilateral cervical spinal cord contusion significantly attenuated the inspiratory activity and motor evoked potential of the diaphragm. Trans-spinal magnetic intermittent theta burst stimulation significantly increased the inspiratory activity of the diaphragm in cervical spinal cord contused rats. Inspiratory bursting was also recruited by trans-spinal magnetic intermittent theta burst stimulation in the rats without diaphragmatic activity after cervical spinal cord injury. In addition, trans-spinal magnetic intermittent theta burst stimulation is associated with increases in oxygen consumption and carbon dioxide production. CONCLUSIONS:These results suggest that trans-spinal magnetic intermittent theta burst stimulation can induce respiratory neuroplasticity. CLINICAL SIGNIFICANCE:We propose that trans-spinal theta burst magnetic stimulation may be considered a potential rehabilitative strategy for improving the respiratory activity after cervical spinal cord injury. This will require future clinical study.

High cervical spinal cord injuries induce permanent neuromotor and autonomic deficits. These injuries impact both central respiratory and cardiovascular functions through modulation of the sympathetic nervous system. So far, cardiovascular studies have focused on models of complete contusion or transection at the lower cervical and thoracic levels and diaphragm activity evaluations using invasive methods. The present study aimed to evaluate the impact of C2 hemisection on different parameters representing vital functions (i.e., respiratory function, cardiovascular, and renal filtration parameters) at the moment of injury and 7 days post-injury in rats. No ventilatory parameters evaluated by plethysmography were impacted during quiet breathing after 7 days post-injury, whereas permanent diaphragm hemiplegia was observed by ultrasound and confirmed by diaphragmatic electromyography in anesthetized rats. Interestingly, the mean arterial pressure was reduced immediately after C2 hemisection, with complete compensation at 7 days post-injury. Renal filtration was unaffected at 7 days post-injury; however, remnant systolic dysfunction characterized by a reduced left ventricular ejection fraction persisted at 7 days post-injury. Taken together, these results demonstrated that following C2 hemisection, diaphragm activity and systolic function are impacted up to 7 days post-injury, whereas the respiratory and cardiovascular systems display vast adaptation to maintain ventilatory parameters and blood pressure homeostasis, with the latter likely sustained by the remaining descending sympathetic inputs spared by the initial injury. A better broad characterization of the physiopathology of high cervical spinal cord injuries covering a longer time period post-injury could be beneficial for understanding evaluations of putative therapeutics to further increase cardiorespiratory recovery.