Spontaneous Functional Recovery Research Articles

Initiating daily acute intermittent hypoxia (dAIH) therapy at 1-week after contusion spinal cord injury (SCI) improves lower urinary tract function in rat

Spinal cord injury (SCI) above the level of the lumbosacral spinal cord produces lower urinary tract (LUT) dysfunction, resulting in impairment of urine storage and elimination (voiding). While spontaneous functional recovery occurs due to remodeling of spinal reflex micturition pathways, it is incomplete, indicating that additional strategies to further augment neural plasticity following SCI are essential. To this end, acute intermittent hypoxia (AIH) exposure has been proposed as a therapeutic strategy for improving recovery of respiratory and other somatic motor function following SCI; however, the impact of AIH as a therapeutic intervention to improve LUT dysfunction remains to be determined. Therefore, we examined the effects of daily AIH (dAIH) on both spontaneous micturition patterns and reflex micturition event (rME) behaviors in adult female Sprague-Dawley rats with mid-thoracic moderate contusion SCI. For these experiments, dAIH gas exposures (five alternating 3 min 12% O2 and 21% O2 episodes) were delivered for 7 consecutive days beginning at 1-week after SCI, with awake micturition patterns being evaluated weekly for 2–3 sessions before and for 4 weeks after SCI and rME behaviors elicited by continuous infusion of saline into the bladder being evaluated under urethane anesthesia at 4-weeks after SCI; daily normoxia (dNx; 21% O2 episodes) served as a control. At 1-week post-SCI, both an areflexic phenotype (i.e., no effective voiding events) and a functional voiding phenotype (i.e., infrequent voiding events with large volumes) were observed in spontaneous micturition patterns (as expected), and subsequent dAIH, but not dNx, treatment led to recovery of spontaneous void frequency pattern to pre-SCI levels; both dAIH- and dNx-treated rats exhibited slightly increased void volumes. At 4-weeks post-SCI, rME behaviors showed increased effectiveness in voiding in dAIH-treated (compared to dNx-treated) rats that included an increase in both bladder contraction pressure (delta BP; P = 0.014) and dynamic voiding efficiency (P = 0.018). Based on the voiding and non-voiding bladder contraction behaviors (VC and NVC, respectively) observed in the BP records, bladder dysfunction severity was classified into mild, moderate, and severe phenotypes, and while rats in both treatment groups included each severity phenotype, the primary phenotype observed in dAIH-treated rats was mild and that in dNx-treated rats was moderate (P = 0.044). Taken together, these findings suggest that 7-day dAIH treatment produces beneficial improvements in LUT function that include recovery of micturition pattern, more efficient voiding, and decreased NVCs, and extend support to the use of dAIH therapy to treat SCI-induced LUT dysfunction.

Autonomic Nerve Fibers Aberrantly Reinnervate Denervated Facial Muscles and Alter Muscle Fiber Population.

The surgical redirection of efferent neural input to a denervated muscle via a nerve transfer can reestablish neuromuscular control after nerve injuries. The role of autonomic nerve fibers during the process of muscular reinnervation remains largely unknown. Here, we investigated the neurobiological mechanisms behind the spontaneous functional recovery of denervated facial muscles in male rodents. Recovered facial muscles demonstrated an abundance of cholinergic axonal endings establishing functional neuromuscular junctions. The parasympathetic source of the neuronal input was confirmed to be in the pterygopalatine ganglion. Furthermore, the autonomically reinnervated facial muscles underwent a muscle fiber change to a purely intermediate muscle fiber population myosin heavy chain type IIa. Finally, electrophysiological tests revealed that the postganglionic parasympathetic fibers travel to the facial muscles via the sensory infraorbital nerve. Our findings demonstrated expanded neuromuscular plasticity of denervated striated muscles enabling functional recovery via alien autonomic fibers. These findings may further explain the underlying mechanisms of sensory protection implemented to prevent atrophy of a denervated muscle.SIGNIFICANCE STATEMENT Nerve injuries represent significant morbidity and disability for patients. Rewiring motor nerve fibers to other target muscles has shown to be a successful approach in the restoration of motor function. This demonstrates the remarkable capacity of the CNS to adapt to the needs of the neuromuscular system. Yet, the capability of skeletal muscles being reinnervated by nonmotor axons remains largely unknown. Here, we show that under deprivation of original efferent input, the neuromuscular system can undergo functional and morphologic remodeling via autonomic nerve fibers. This may explain neurobiological mechanisms of the sensory protection phenomenon, which is because of parasympathetic reinnervation.

Спонтанне посттравматичне відновлення рухової функції задньої кінцівки самців мишей

We studied the level of spontaneous post-traumatic recovery of motor function in male FVB mice. The left-side spinal cord hemisection was a model of damage. The locomotor activity and spasticity of the hindlimb were determined using the BBB and B scales and the Ashword scale during the first 12 weeks of the post-traumatic period. According to the results of the experimental study, at a later date in the post-traumatic period, the restoration of the function of the hind limb was observed at the level of 3.22 ± 0.46 points (out of 21 possible) on the BBB scale and 1.88 ± 0.27 points (out of 9 possible) on the B scale. Such indicators of hind limb locomotor activity conform to the phase of early recovery. However, at all studied time intervals after spinal cord injury, a consistently high level of hindlimb spasticity in experimental animals was noted – 3.17 ± 0.46 (out of 4 possible) on the Ashword scale.

CD200R1 Contributes to Successful Functional Reinnervation after a Sciatic Nerve Injury.

Activating and inhibitory immune receptors play a critical role in regulating systemic and central nervous system (CNS) immune and inflammatory processes. The CD200R1 immunoreceptor induces a restraining signal modulating inflammation and phagocytosis in the CNS under different inflammatory conditions. However, it remains unknown whether CD200R1 has a role in modulating the inflammatory response after a peripheral nerve injury, an essential component of the successful regeneration. Expression of CD200R1 and its ligand CD200 was analyzed during homeostasis and after a sciatic nerve crush injury in C57Bl/6 mice. The role of CD200R1 in Wallerian Degeneration (WD) and nerve regeneration was studied using a specific antibody against CD200R1 injected into the nerve at the time of injury. We found an upregulation of CD200R1 mRNA after injury whereas CD200 was downregulated acutely after nerve injury. Blockade of CD200R1 significantly reduced the acute entrance of both neutrophils and monocytes from blood after nerve injury. When long term regeneration and functional recovery were evaluated, we found that blockade of CD200R1 had a significant effect impairing the spontaneous functional recovery. Taken together, these results show that CD200R1 has a role in mounting a successful acute inflammatory reaction after injury, and contributes to an effective functional recovery.

Spontaneous partial recovery of striatal dopaminergic uptake despite nigral cell loss in asymptomatic MPTP-lesioned female minipigs

The Göttingen minipig is a large animal with a gyrencephalic brain that expresses –complex behavior, making it an attractive model for Parkinson’s disease research. Here, we investigate the temporal evolution of presynaptic dopaminergic function for 14 months after injections of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the minipig using a multi-tracer longitudinal positron emission tomography (PET) design. We injected seven sedated minipigs with 1–2 mg/kg of MPTP, and two with saline, three times a week over four weeks. We monitored behavioral deficits using a validated motor scale and walking mat. Brains were imaged with (+)-⍺-[11C]-dihydrotetrabenazine ([11C]-DTBZ) and [18F]-dihydroxyphenylalanine ([18F]-FDOPA) PET at baseline and 1, 3, 10 and 14 months after MPTP injection, and immunohistochemistry was used to assess nigral cell loss. The minipigs showed mild bradykinesia and impaired coordination at early timepoints after MPTP. PET revealed decreases of striatal [11C]-DTBZ and [18F]-FDOPA uptake post-MPTP with partial spontaneous recovery of [18F]-FDOPA after 10 months. Postmortem analysis estimated an MPTP-induced nigral loss of 57% tyrosine hydroxylase+ and 43% Nissl-stained cells. Normal motor function despite substantial damage to the dopaminergic system is consistent with prodromal Parkinson’s disease, and offers an opportunity for testing disease-modifying therapies. However, partial spontaneous recovery of dopamine terminal function must be taken into account in future studies.

Ampakine CX717 Stimulates Diaphragm Activity following Mid‐cervical Spinal Contusion Injury

Cervical spinal cord injuries result in significant respiratory compromise and there is a need to develop therapies to counter respiratory insufficiency in this patient population. Ampakines are positive allosteric modulators of AMPA receptors, and can stimulate breathing during states of hypoventilation, such as following opioid overdose or in neuromuscular disorders. Our laboratory has previously shown that acute treatment with ampakine CX717 can stimulate phrenic activity in spinally injured animals under urethane anesthesia. Recently, we extended these findings by showing that a low dose of CX717 was sufficient to enhance diaphragm electromyography (EMG) activity and tidal volume in unanaesthetized animals with a C2 hemisection injury. The next step in the translational pathway, and the goal of the current study, was to test the efficacy of ampakines in a model of contusion injury that is more similar to the injuries typically experienced by humans. The C4 contusion injury used in the current study results in direct phrenic motor neuron loss and significant damage of the spinal pathways innervating respiratory motor pools. This model is also associated with strong spontaneous recovery of diaphragm function, such that pronounced deficits are likely to be detected only in the initial week following injury. Animals were implanted with in‐dwelling bilateral diaphragm EMG electrodes and ventilation was measured using whole body plethysmography. At 4 and 14 days following a 150 kDy C4 unilateral contusion injury (C4Ct), male and female rats were given a single intravenous bolus of CX717 (5 mg/kg, n=4) or vehicle (2‐hydroxypropyl‐beta‐cyclodextrin; HPCD; n=4). At the 4‐day time point, infusion of CX717 increased peak diaphragm EMG (recorded ipsilateral to C4Ct) by 40‐50% when compared to vehicle group. Respiratory rate was also elevated in the CX717 group by 80% post‐infusion, indicating a likely supraspinal mechanism of the impact of ampakines. In the CX717 group, tidal volume was increased by 25±13% during infusion, 20±16% at 5 min post infusion and returned to baseline levels by 15 mins post CX717 infusion. There was no change in tidal volume in the vehicle group. During an acute respiratory challenge with hypoxia (10% O2), CX717 treated animals were able to increase diaphragm EMG (100±15%) to a greater extent as compared to vehicle (50 ± 23%, P=0.004). Similarly, during a combined hypoxia‐hypercapnia challenge (10% O2, 7% CO2), CX717 treated animals displayed an increased diaphragm EMG response (200±44%) compared to vehicle (100 ± 55%, P=0.0144). In contrast to the 4‐day data, there was no discernable impact of ampakines on baseline or challenged breathing at 14 days post C4Ct. This is perhaps not surprising because prior work establishes that in this injury model, robust compensation has occurred after 2 weeks, and deficits in diaphragm activation are difficult to detect. In summary, our data indicate that low dose, low impact ampakine treatment can increase diaphragm muscle output at an acute timepoint following mid‐cervical contusion type injuries. These studies pave the path for future experiments to test if ampakine treatment can be combined with rehabilitation techniques to further enhance the therapeutic effect of ampakines in this injury model.

Weekly Acute Intermittent Hypoxia Elicits Sustained Beneficial Improvements in Reflex Bladder Function in Rats with Moderate Contusion SCI

Acute intermittent hypoxia (AIH) administered either as daily or weekly therapy has been shown to improve both respiratory and motor function in preclinical and clinical studies in spinal cord injury (SCI). SCI can also severely impact bladder function, leading to problems with urine storage and emptying of the bladder that include detrusor overactivity, decreased voiding efficiency, and increased residual volume. Ongoing work in our laboratory has been evaluating the impact of AIH treatments delivered as either a single episode or daily episodes for 7 consecutive days as a strategy to promote improvements in bladder function in rats with moderate contusion SCI. In our studies, a single AIH treatment results in immediate short‐term reductions in bladder overactivity (i.e., non‐voiding bladder contractions, NVCs) and induction of more efficient voiding, while daily (7‐d) AIH treatments result in sustained similar improvements and restoration of urination pattern. In the current study, we investigated the effects of weekly AIH (wAIH) treatment administered 3x per week for 4 weeks on SCI‐induced bladder dysfunction in adult female SD rats with mid‐thoracic moderate contusion SCI. wAIH treatment consisted of five alternating 3‐min episodes of 12% O2 and 21% O2 and was initiated 4 weeks after SCI; weekly normoxia (wNx; 21% O2 episodes using the same timing) served as a gas delivery control. Prior to initiating weekly gas treatments, the magnitude of SCI‐induced deficits and progression of spontaneous recovery of both hindlimb motor function (BBB scores) and lower urinary tract (LUT) function (manual expression of urine volumes during post‐operative care) were assessed. These measurements revealed that the deficits and initial stages of recovery were similar in rats assigned to both treatment groups. 2 weeks after completion of the weekly gas treatments (which corresponds to 10 weeks after SCI), reflex bladder function was assessed during bladder filling and voiding in urethane‐anesthetized rats. For these experiments, reflex micturition events (rMEs) were elicited by continuous infusion of saline (0.04‐0.09 ml/min) into the bladder while intravesical bladder pressure (BP) was continuously measured. We found that in nearly all of the wAIH‐treated rats (~86%), the BP record during filling was characterized by an almost complete absence of NVCs per voiding contraction (VC), while in nearly all of the wNx‐treated rats (~80%), the BP record during filling was characterized by a severe degree of LUT dysfunction that included 3‐10 NVCs preceding each VC. Comparisons of VC features between these groups of rats revealed that wNx‐treated rats exhibited long inter‐contraction intervals (ICI; despite higher infusion rates; P=0.0326) and correspondingly larger fill (P=0.0187) and void (P=0.0029) volumes while wAIH‐treated rats exhibited shorter contraction duration (P=0.0381) and contraction area (P=0.0110). These findings suggest that wAIH treatment elicits sustained beneficial improvements in rME behaviors, resulting in a mild degree of LUT dysfunction in rats with chronic SCI.

Longitudinal assessment of network reorganizations and language recovery in postoperative patients with glioma.

For patients with glioma located in or adjacent to the linguistic eloquent cortex, awake surgery with an emphasis on the preservation of language function is preferred. However, the brain network basis of postoperative linguistic functional outcomes remains largely unknown. In this work, 34 patients with left cerebral gliomas who underwent awake surgery were assessed for language function and resting-state network properties before and after surgery. We found that there were 28 patients whose language function returned to at least 80% of the baseline scores within 3 months after surgery or to 85% within 6 months after surgery. For these patients, the spontaneous recovery of language function synchronized with changes within the language and cognitive control networks, but not with other networks. Specifically, compared with baseline values, language functions and global network properties were the worst within 1 month after surgery and gradually recovered within 6 months after surgery. The recovery of connections was tumour location dependent and was attributed to both ipsihemispheric and interhemispheric connections. In contrast, for six patients whose language function did not recover well, severe network disruptions were observed before surgery and persisted into the chronic phase. This study suggests the synchronization of functional network normalization and spontaneous language recovery in postoperative patients with glioma.

Advances and future directions in the care of patients with facial paralysis

Advances and future directions in the care of patients with facial paralysis

Abstract 86: Dicer Ablation In Oligodendrocytes Impairs Oligodendrogenesis And Functional Recovery After Stroke

Introduction: Stroke-induced oligodendrogenesis contributes to ischemic brain remodeling and spontaneous functional recovery. Genes that regulate microRNA biogenesis in stroke-induced oligodendrogenesis remain little known. Methods: We employed a transgenic mouse line with conditional and inducible ablation of Dicer, a key gene of miRNA biogenesis, in myelin proteolipid protein (PLP) lineage oligodendrocytes (Dicer-KO). A PLP reporter mouse line was used as a control. Mice were subjected to transient (60min) middle cerebral artery occlusion (MCAO, n=8/group). An array of behavioral and cognitive tests were performed. All mice were sacrificed at 28 days after MCAO. Fluorescence-activated cell sorting (FACS) in combination with miRNA sequencing were used to profile the miRNA alteration. Results: Compared to ischemic reporter mice, ischemic Dicer-KO mice exhibited significantly increased infarct volumes and significantly impaired neurological outcomes and cognitive deficits post stroke as assayed by social recognition memory, novel object recognition, and Morris water-maze tests. Immunochemistry analysis revealed that ischemic Dicer-KO mice showed a significant reduction of the number of PLP-lineage NG2 + oligodendrocyte precursor cells (OPCs) and APC + myelinating oligodendrocytes compared to ischemic reporter mice. Moreover, Dicer-KO mice exhibited a robust reduction of myelinated axons measured by myelin binding protein (MBP) and Bielschowsky/Luxol Fast Blue assay. FACS analysis of PLP-lineage cells in peri-infarct regions showed that ablation of Dicer significantly decreased many miRNAs including the miR-200 family that are known to regulate oligodendrogenesis. Conclusion: Our data indicate that Dicer in PLP lineage oligodendrocytes is required for stroke-induced oligodendrogenesis and myelination, and that Dicer is involved in spontaneous functional recovery after stroke.

Acute renal failure secondary to EBV in a 21-year-old healthy male: a case report

Epstein-Barr virus (EBV) affects 9 out of 10 people at some point in their lives. Though generally a benign infection, it can present with a plethora of symptoms and complications. We present the case of a 21-year-old previously healthy male suffering from EBV who presented with an 8-day history of odynophagia, pharyngitis, cough, abdominal pain and fatigue, previously he also had a fever which reached a maximum of 38.5°C. The patient’s clinical exam was positive only for abdominal tenderness. During his hospitalisation for EBV, our patient suffered sudden renal failure over the course of 4 days, with a glomerular filtration rate dropping to 33 mL/min/1.73 m2, before spontaneously recovering to normal levels. This occurred with supportive treatment only and without the use of corticosteroids. This case illustrates an atypical presentation of EBV infection and provides a further example of spontaneous recovery of renal function.

A flexible metal nano-mesh strain sensor with the characteristic of spontaneous functional recovery after fracture damage

Developing flexible sensors with high sensitivity, a wide sensing range, and good stability is a challenge. By replicating the anodic aluminum oxide (AAO) hole structure, we proposed new strain sensors with Pt nano-mesh films embedded in polydimethylsiloxane (PDMS) films. The nano-mesh strain sensor exhibited high sensitivity (a gauge factor of 4500) and a sensing range as high as 90%. The resistance remained almost completely unchanged after 1500 loading/unloading cycles of 15% strain, demonstrating the high repeatability and stability of the sensor. In addition, even if the nano-mesh experienced an open circuit by overstraining, the sensor can still measure strain within 45% after recovery. The capability of spontaneous functional recovery after fractural damage considerably extends its service life. Finally, the nano-mesh strain sensors were worn on the wrist and neck to monitor wrist movement and throat vibration, respectively. Signals corresponding to swallowing, throat clearing, and letter pronunciation were clearly distinguished from the peak value and signal patterns. These results indicate that the metal nano-mesh strain sensors have great potential for applications in wearable devices, electronic skin, and flexible robotics.

Targeting the motor cortex to restore walking after incomplete spinal cord injury.

Targeting the motor cortex to restore walking after incomplete spinal cord injury.

Reversible Takotsubo cardiomyopathy with non‐revascularized concomitant severe coronary artery disease

Takotsubo cardiomyopathy is a transient cardiac condition commonly triggered by a stressor, presenting with clinical features mimicking acute coronary syndromes. We report an unusual case of Takotsubo cardiomyopathy in a man with severe three-vessel coronary artery disease awaiting coronary bypass surgery who developed rapid spontaneous recovery of cardiac function before revascularization.

Expression of Slit and Robo during remodeling of corticospinal tract in cervical spinal cord in middle cerebral artery occlusion rats.

Slits and Robos were associated with the generation of axons of corticospinal tract during the corticospinal tract (CST) remodeling after the cerebral ischemic stroke (CIS). However, little is known about the mechanism of CST remodeling. In this study, we detected the expression of Slits and Robos in middle cerebral artery occlusion (MCAO) rats to investigate the roles of Slits and Robos in the CIS. MCAO model was established using modified Zea Longa method. Beam walking test (BWT) was conducted to evaluate the motor function. The images of the track of cortical spinal cord beam on day 7, 14 and 21 were observed by anterograde CST tracing. Biopinylated dextan amine (BDA) was used to mark CST anterogradely. Expression of GAP-43 mRNA and GAP-43 protein in cervical spinal cord was detected by Real-Time PCR and Western blot analysis, respectively. The expression of Slit1, Slit2 and Robo1 in cervical spinal cord was detected by immunofluorescence staining. The scores in the model group were significantly reduced compared to sham-operation group on day 7 (P < 0.001), 14 (P < 0.001) and 21 (P < 0.001), respectively. There was no significant difference in the score on day 7, 14 and 21 of the sham-operation groups (P > 0.05). In contrast, significant increase was noticed in the scores in model group, presenting a time-dependent manner. More CST staining fibers could be observed at the degenerative side in the model group compared with that of the sham-operation group on day 21. GAP-43 mRNA expression in the model group showed significant increase compared to that of sham-operation group on day 14 (P = 0.015) and 21days (P = 0.002). The expression of GAP-43 protein in model group showed significant increase compared to that of sham-operation group on day 14 (P = 0.022) and day 21 (P = 0.008), respectively. The expression of Slit1 and Slit2 showed increase on day 14 and day 21, while the expression of Robo1 showed significant decrease in MCAO rats. Up-regulation of Slit1 and Slit2 and the downregulation of Robo1 may be related to the axons of CST midline crossing in spinal cord of MCAO rat during the spontaneous recovery of impaired motor function.

Spontaneous vegetation succession and recovery of ecosystem structure and function in a 40-year abandoned stone quarry in a Mexican tropical dryland

Background: The restoration of sites degraded by stone quarrying in drylands requires expensive interventions. However, these interventions cannot be used in tropical drylands because rural communities lack financial resources. Spontaneous vegetation succession may help restore degraded sites. However, spontaneous succession is evaluated by only comparing species composition between degraded and reference sites, without considering the structure and function of degraded sites. Question: Can spontaneous succession restore the structure and function of sites degraded by stone quarrying? Study sites and dates: San Rafael Coxcatlán, Puebla, 2013. Methods: We evaluated nine indicators of ecosystem structure and function in 4 degraded sites abandoned for 40 years and 1 reference site. Results: Spontaneous succession partially restored the structure and function of degraded sites. In all degraded sites, herb cover (20-49 %) and biocrust cover (21-51 %) were similar to those in reference site (19 %, 56 %). Three degraded sites also had canopy covers (57-76 %), shrub covers (51-52 %), and bare ground covers (2-3 %) similar to those in reference site (80 %, 42 %, 2 %). However, one degraded site displayed the opposite pattern (32 %, 8 %, 14 %). All degraded sites had lower tree cover (0-2 %), visual obstruction (6-25 %), and litter cover (3-30 %) than the reference site (21 %, 66 %, 77 %). Conclusions: Spontaneous succession helped restore the structure and function in some degraded sites.

Development of Cardiac Events and Functional Recovery Prediction Models for Pediatric Dilated Cardiomyopathy.

Background: Since both the risk of death and the probability of spontaneous functional recovery (FR) coexist in association with pediatric dilated cardiomyopathy (DCMP), management should be based on individualized outcome predictions.Methods: A single-center retrospective review of 105 pediatric patients (age at presentation ≤ 18 years) with DCMP, managed between 1994 and 2017, was performed. Logistic regression was conducted to identify variables associated with FR and cardiac events (CEs), i.e., death or heart transplantation (HTPL), within 2 years after initial presentation. Two outcome prediction models were formulated using these variables.Results: Twenty-six (24.8%) and 51 patients (48.6%) experienced FR and CE, respectively, within 2 years after initial presentation. Predictors of mortality without HTPL were earlier era at presentation (HR: 4.13; 95% CI: 1.88–9.06; p < 0.001) and significant TR (≥moderate; HR: 4.31; 95% CI: 1.26–14.77; p = 0.020) in multivariable Cox regression model. Predictors of FR were recent era (HR: 4.49; 95% CI: 1.40–14.44; p = 0.0012), younger age at initial presentation (HR: 0.98 per 1 month increase; 95% CI: 0.97–0.99, p < 0.001), post-myocarditis DCMP (HR: 4.29; 95% CI: 1.32–13.93; p = 0.015), and arrhythmia-mediated DCMP (HR: 26.88; 95% CI: 2.61–276.70; p = 0.006). Risk factors for CEs was idiopathic DCMP (HR: 2.95; 95% CI: 1.32–6.56, p = 0.008). The low-risk group who had higher probability of FR than CE in prediction model had a slightly higher overall survival rate (71.4 vs. 52.2% at 10 years after presentation; log-rank p = 0.09) and a significantly higher HTPL-free survival rate (67.5 vs. 24.9% at 10 years after presentation; log-rank p < 0.001) than the high-risk group.Conclusions: Prognostication and management strategies for pediatric DCMP may be enhanced by risk stratification using outcome prediction modeling.

The Histopathology of Severe Graded Compression in Lower Thoracic Spinal Cord Segment of Rat, Evaluated at Late Post-injury Phase

Spontaneous recovery of lost motor functions is relative fast in rodent models after inducing a very mild/moderate spinal cord injury (SCI), and this may complicate a reliable evaluation of the effectiveness of potential therapy. Therefore, a severe graded (30 g, 40 g and 50 g) weight-compression SCI at the Th9 spinal segment, involving an acute mechanical impact followed by 15 min of persistent compression, was studied in adult female Wistar rats. Functional parameters, such as spontaneous recovery of motor hind limb and bladder emptying function, and the presence of hematuria were evaluated within 28 days of the post-traumatic period. The disruption of the blood-spinal cord barrier, measured by extravasated Evans Blue dye, was examined 24 h after the SCI, when maximum permeability occurs. At the end of the survival period, the degradation of gray and white matter associated with the formation of cystic cavities, and quantitative changes of glial structural proteins, such as GFAP, and integral components of axonal architecture, such as neurofilaments and myelin basic protein, were evaluated in the lesioned area of the spinal cord. Based on these functional and histological parameters, and taking the animal’s welfare into account, the 40 g weight can be considered as an upper limit for severe traumatic injury in this compression model.

A comparison of accelerometric monitoring by TOF Watch® SX and electromyographic monitoring by Tetragraph® for recovery from neuromuscular blockade

BackgroundNeuromuscular monitoring has become a standard of care for management of anesthesia. While acceleromyography (AMG) is the most common technology used in clinical practice, guidelines suggest that electromyographic (EMG) devices are ideal for quantitative neuromuscular monitoring. The Tetragraph® is an EMG monitor that has recently been marketed. Study objectiveThe aim of this study is to assess the agreement during recovery from neuromuscular blockade of this new monitor with the TOF Watch® SX, and to compare intraobserver variability for the two devices. DesignSingle-center, prospective, observational clinical study. SettingOperating room. PatientsTwenty-three patients were enrolled and twenty patients were included in the analysis. InterventionA comparison of TOF-ratios measured sequentially from the same hand with the Tetragraph and TOF Watch SX was conducted during spontaneous recovery of neuromuscular function from patients that received rocuronium during surgery. Main outcome measuresWe used Bland-Altman plots for repeated measures to compare TOF-ratios obtained sequentially by the two devices. Subsequent measures with the same device were used to calculate intraobserver variability for each monitor. Main resultsThe bias between AMG and EMG for TOF-ratios range between 0.2 and 1.0 was 0.13 (95% CI 0.08 to 0.18) and the limits of agreement (LoA) were − 0.11 (95% CI -0.20 to −0.06) and 0.37 (95% CI 0.32 to 0.46), respectively. Agreement slightly improved for TOF-ratios higher than 0.8 compared with lower TOF-ratios: the bias was 0.12 (95% CI 0.08 to 0.17) and 0.13 (95% CI 0.08 to 0.19), respectively. EMG relative intraobserver variability was lower compared with AMG (2.0%, IQR 0.0% to 4.5% vs. 3.2%, IQR 1.2% to 6.0%, P = 0.001). ConclusionsBias between the TOF Watch SX and the Tetragraph TOF-ratios is in line with previous results for AMG and EMG monitors.

Effects of early exercise training on the severity of autonomic dysreflexia following incomplete spinal cord injury in rodents.

Hemodynamic instability and cardiovascular (CV) dysfunction are hallmarks of patients living with cervical and high thoracic spinal cord injuries (SCI). Individuals experience bouts of autonomic dysreflexia (AD) and persistent hypotension which hamper the activities of daily living. Despite the widespread use of exercise training to improve health and CV function after SCI, little is known about how different training modalities impact hemodynamic stability and severity of AD in a model of incomplete SCI. In this study, we used implantable telemetry devices to assess animals with T2 contusions following 3.5 weeks of exercise training initiated 8 days post‐injury: passive hindlimb cycling (T2‐CYC, n = 5) or active forelimb swimming (T2‐SW, n = 6). Uninjured and non‐exercised SCI control groups were also included (CON, n = 6; T2‐CON, n = 7; T10‐CON, n = 6). Five weeks post‐injury, both T2‐CON and T2‐CYC presented with resting hypotension compared to uninjured CON and T10‐CON groups; no differences were noted in resting blood pressure in T2‐SW versus CON and T10‐CON. Furthermore, pressor responses to colorectal distention (AD) were larger in all T2‐injured groups compared to T10‐CON, and were not attenuated by either form of exercise training. Interestingly, when T2‐injured animals were re‐stratified based on terminal BBB scores (regardless of training group), animals with limited hindlimb recovery (T2‐LOW, n = 7) had more severe AD responses. Our results suggest that the spontaneous recovery of locomotor and autonomic function after severe but incomplete T2 SCI also influences the severity of AD, and that short periods (3.5 weeks) of passive hindlimb cycling or active forelimb swimming are ineffective in this model.