Cord Level Research Articles

Cannabinoids and General Anesthetics: Revisiting Molecular Mechanisms of Their Pharmacological Interactions.

Cannabis has been used for recreation and medical purposes for more than a millennium across the world; however, its use's consequences remain poorly understood. Although a growing number of surgical patients are regular cannabis consumers, little is known regarding the pharmacological interactions between cannabis and general anesthetics; consequently, there is not a solid consensus among anesthesiologists on the perioperative management of these patients. The existing evidence about the molecular mechanisms underlying pharmacological interactions between cannabinoids and anesthetic agents, both in animal models and in humans, shows divergent results. While some animal studies have demonstrated that phytocannabinoids (tetrahydrocannabinol [THC], cannabidiol [CBD], and cannabinol [CBN]) potentiate the anesthetic effects of inhalation and intravenous anesthetics, while others have found effects comparable with what has been described in humans so far. Clinical studies and case reports have consistently shown increased requirements of GABAergic anesthetic drugs (isoflurane, sevoflurane, propofol, midazolam) to achieve adequate levels of clinical anesthesia. Several potential molecular mechanisms have been proposed to explain the effects of these interactions. However, it is interesting to mention that in humans, it has been observed that the ingestion of THC enhances the hypnotic effect of ketamine. Animal studies have reported that cannabinoids enhance the analgesic effect of opioids due to a synergistic interaction of the endogenous cannabinoid system (ECS) with the endogenous opioid system (EOS) at the spinal cord level and in the central nervous system. However, human data reveals that cannabis users show higher scores of postoperative pain intensity as well as increased requirements of opioid medication for analgesia. This review aims to improve understanding of the molecular mechanisms and pharmacological interactions between cannabis and anesthetic drugs and the clinical outcomes that occur when these substances are used together.

The participation of monoamines in the realization of vasopressin analgesic effects during electrical stimulation of paws in rats

BACKGROUND: Arginine vasopressin has been implicated in the modulation of stress and pain. The influence of a synthetic analogue of arginine vasopressin, 1-deamino-8-D-arginine-vasopressin, оn pain sensitivity, stress reactivity, levels of monoamines and brain neurotrophic factor in a model of paw electrical stimulation in rats has not been studied. AIM: The aim was to evaluate the effect of a synthetic vasopressin analog, 1-deamino-8-D-arginine-vasopressin, on pain sensitivity and the content of norepinephrine, serotonin, dopamine, brain neurotrophic factor in the parietal cortex and spinal cord in electrocutaneous paw stimulation test in rats. MATERIALS AND METHODS: The study was conducted on male Wistar rats who were injected with 1-deamino-8-D-arginine-vasopressin intranasally once a day for 5 days in small (single 20 ng, course 100 ng) and large doses (single 2 ug, course 10 ug). The content of brain neurotrophic factor in the parietal cortex and spinal cord, and corticosterone in blood serum were determined using enzyme immunoassay. The levels of norepinephrine, serotonin, dopamine and their metabolites in the brain were evaluated using high-performance liquid chromatography. RESULTS: 1-Deamino-8-D-arginine-vasopressin in different doses reduced pain sensitivity in rats, more pronounced when administered in large doses. The peptide in small doses in the parietal cortex increased the content of dopamine and reduced the levels of 5-hydroxyindolacetic acid, a metabolite of serotonin; in the spinal cord, it reduced the content of 5-hydroxyindolacetic acid. 1-Deamino-8-D-arginine-vasopressin in high doses in the parietal cortex increased the content of dopamine and reduced the levels of 5-hydroxyindolacetic acid; in the spinal cord ― reduced the content of serotonin and 3,4-dihydroxyphenylacetic acid, a metabolite of dopamine; increased the levels of norepinephrine and homovanilic acid, a metabolite of dopamine. The peptide had no effect on corticosterone levels in the blood and brain neurotrophic factor levels in the brain in rats. CONCLUSIONS: The analgesic effects of 1-deamino-8-D-arginine-vasopressin were revealed with intranasal administration in different subendocrine doses. Regardless of the administered doses, dopamine and serotonin at the supraspinal level were involved in peptide-induced anesthesia; serotonin at the spinal cord level. More pronounced analgesia with the administration of 1-deamino-8-D-arginine-vasopressin in high doses was due to the additional involvement of dopamine and norepinephrine at the spinal cord level.

New insights in the mechanisms of opioid analgesia and tolerance: Ultramicronized palmitoylethanolamide down-modulates vascular endothelial growth factor-A in the nervous system

Growing evidence suggests that opioid analgesics modulate angiogenesis during pathophysiological processes. Vascular endothelial growth factor-A (VEGF-A) was recently proposed to be involved in pain development. To date, no anti-angiogenic drug is used for pain management. When administered in a bioavailable formulation, (i.e., ultramicronized) N-palmitoylethanolamine (PEA) delays the onset of morphine tolerance, improves morphine analgesic activity and reduces angiogenesis in in vivo models. This study aimed at investigating whether VEGF-A is involved in PEA-induced delay of morphine tolerance. The anti-VEGF-A monoclonal antibody bevacizumab was used as a reference drug. Preemptive and concomitant treatment with ultramicronized PEA delayed morphine tolerance and potentiated the analgesic effect of morphine, while counteracting morphine-induced increase of VEGF-A in the nervous system. Similar results were obtained when bevacizumab was administered together with morphine. Of note, bevacizumab showed an analgesic effect per se. In equianalgesic treatment regimens (obtained through increasing morphine doses and associating PEA), PEA resulted in lower expression of VEGF-A in dorsal root ganglia (DRG) and spinal cord compared to morphine alone. Similar results were observed for plasma levels of the soluble VEGF receptor 1 (sFLT-1). Moreover, in morphine-treated animals, two pain-related genes (i.e., Serpina3n and Eaat2) showed a more than 3-fold increase in their expression at spinal cord and DRG level, with the increase being significantly counteracted by PEA treatment. This study supports the hypothesis that the effects of PEA on morphine analgesia and tolerance may be mediated by the down-modulation of VEGF-A and sFLT-1 in the nervous system and plasma, respectively.

Clinical risk factors associated with the need for tracheostomy in traumatic cervical and high thoracic spinal cord injury

BackgroundOur objective was to assess the association of completeness and level of spinal cord injury (SCI) with the need for tracheostomy and identify additional risk factors predictive of tracheostomy. MethodsThis was a retrospective review of patients with SCI between January 2017 and December 2022. ResultsPatients with complete SCI were roughly thirty-three times more likely to have a tracheostomy when compared to incomplete injury (82 ​% vs 12 ​%, p ​< ​0.001, OR ​= ​32.9). The rate of tracheostomy did not differ between spinal cord levels for complete (p ​= ​0.68) or incomplete (p ​= ​0.08) injuries. Penetrating injury, low GCS, high ISS, and polytrauma were associated with tracheostomy need in incomplete SCI. ConclusionComplete injury was statistically significantly associated with the need for tracheostomy while level of injury failed to reach significance. Patients with incomplete SCI that have certain clinical risk factors should be considered for early tracheostomy.

ALDEHYDE DEHYDROGENASE-2 DEFICIENCY AGGRAVATES NEUROINFLAMMATION, NOCICEPTION, AND MOTOR IMPAIRMENT IN A MOUSE MODEL OF MULTIPLE SCLEROSIS.

Aldehyde dehydrogenase-2 deficiency (ALDH2*2) found in 36% of Han Chinese, affects approximately 8% of the world population. ALDH2 is a mitochondrial key enzyme in detoxifying reactive aldehydes to less reactive forms. Studies demonstrate a potential link between ALDH2*2 mutation and neurodegenerative diseases. Multiple sclerosis (MS) is an incurable and disabling neurodegenerative autoimmune disease that induces motor, and cognitive impairment, and hypersensitivity, including chronic pain. Accumulating evidence suggests that reactive aldehydes, such as 4-hydroxynonenal (4-HNE), contribute to MS pathogenesis. Here, using knock-in mice carrying the inactivating point mutation in ALDH2, identical to the mutation found in Han Chinese, we showed that the impairment in ALDH2 activity heightens motor disabilities, and hypernociception induced by experimental autoimmune encephalomyelitis (EAE). The deleterious clinical signs are followed by glial cell activation in the spinal cord and increased 4-HNE levels in the spinal cord and serum. Importantly, the pharmacological ALDH2 activation by Alda-1 ameliorates EAE-induced hypernociception and motor impairment in both wild-type and ALDH2*2KI mice. Reduced hypernociception was associated with less early growth response protein 1 (EGR1), neuronal and glial activation, and reactive aldehyde accumulation in the spinal cord and serum. Taken together, our data suggest that the mitochondrial enzyme ALDH2 plays a role in regulating clinical, cellular, and molecular responses associated with EAE. This indicates that ALDH2 could serve as a molecular target for MS control, with ALDH2 activators, like Alda-1 as potential neuroprotective candidates. Furthermore, ALDH2*2 carriers may be at increased risk of developing more accentuated MS symptoms.

Atractylenolide-I Ameliorates Motor Deficits and Reduces Inflammation of the Spinal Cord by SIRT1/PGC-1α Pathway in MPTP Subacute Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative movement disorder that impacts various systems, including the substantia nigra (SN) par compacta (SNpc) and extranigral regions like the spinal cord. The presence of persistent inflammation in the SN and spinal cord is associated with movement difficulties in PD. Atractylenolide-I (ATR-I) is a natural sesquiterpene recognized for its anti-inflammatory and neuroprotective effects. This research aimed to assess the impact of ATR-I treatment on motor function and inflammation in MPTP-induced subacute PD mice, particularly focusing on the role of ATR-I in spinal cord inflammation. The motor functions of the mice were assessed using suspension and gait tests. Dopaminergic neuronal loss in the SNpc and microglial activation in both the SNpc and spinal cord were evaluated through immunofluorescence staining. The levels of inflammatory mediators in the spinal cord were measured using RT-qPCR analysis. The expressions of SIRT1 and PGC-1α in the spinal cord were analyzed through Western blotting and RT-qPCR. ATR-I treatment improved motor deficits in MPTP-induced mice. Moreover, ATR-I reduced the loss of dopamine neurons and microglial activation in the SNpc of MPTP-induced mice. Additionally, ATR-I suppressed spinal cord inflammation by decreasing microglial activation and the mRNA expression of TNF-α, IL-1β, and iNOS in MPTP-induced mice. Interestingly, ATR-I also upregulated SIRT1 and PGC-1α levels in the spinal cord of MPTP-induced mice. These findings suggest that ATR-I exhibits anti-inflammatory and neuroprotective properties in PD. The attenuation of spinal cord inflammation via the SIRT1/PGC-1α pathway may contribute to enhancing motor function, highlighting ATR-I as a potential therapeutic avenue for PD.

Factors affecting Umbilical Cord Vitamin D Concentration and Its Association with Maternal Vitamin D Level

Objective: To analyze factors affecting maternal and umbilical cord levels of vitamin D and to understand the correlation between maternal and umbilical cord vitamin D levels.Methods: This was a cross-sectional study conducted at the department of pediatrics of Dr. D. Y. Patil Medical College and Research Centre, Pune, India. Maternal and umbilical cord vitamin D levels were examined in 300 pairs of mother and child over a period of two years. Informed consent was obtained from all participants. The vitamin D level was measured using chemiluminescent immunoassay and classified as either deficient, insufficient or adequate depending on specific cut-offs. Correlations between maternal and neonatal vitamin D levels and demographic factors like religion, socioeconomic status, and sun exposure were also exlored. Statistical tests were performed using the SPSS 21.0 software, with p&lt;0.05 deemed P-valueas significant.Results: There was significantly high prevalence of vitamin D deficiency in neonates, (78.67%). Key factors influencing maternal vitamin D levels were religion (p=0.027), maternal education (p=0.003), gravida status (p=0.035), and sunlight exposure, with sunlight exposure showing a very strong correlation to the deficiency (p&lt;0.001). Moreover, maternal serum calcium levels significantly affected vitamin D status (p&lt;0.001). A significant association was observed between maternal and cord blood vitamin D levels, with the maternal vitamin D level strongly predicted vitamin D status in neonates (p&lt;0.001).Conclusion: The umbilical cord vitamin D level strongly correlates with the maternal vitamin D level, which is significantly affected by maternal education, residence, pregnancy status, gestational age, and sun exposure.

The mediating role of abnormal ZEB1 methylation in the association between nickel exposure and non-syndromic orofacial cleft

Our previous study found a positive relationship between fetal nickel exposure and the risk of OFCs. The teratogenic mechanism of nickel is not clear. In this study, we aim to examine the mediating effect of DNA methylation on the association of nickel(Ni) exposure with NSOFC in fetuses. 10 cases and 10 controls was used for screening target gene by Illumina Infinium Methylation EPIC(850k) BeadChip. 36 cases and 78 controls was conducted to determine DNA methylation level of selected gene in umbilical cord blood by Mass spectrometry assay. Mediation analysis was used to evaluate the potential mediating effect of selected gene methylation on the relation between concentrations of Ni and the risk for NSOFC. In the discovery stage, ZEB1 gene was identified to be hypermethylated in both nickel exposure and NSOFC group for validation. In the verification stage, the overall average methylation level of ZEB1 was significant higher in NSOFC cases(median = 8.70, interquartile range(IQR): 5.75–11.53) as compared to controls (median = 5.35, IQR: 4.30–7.78). The risk for NSOFC was increased by 1.43-fold with hypermethylation of ZEB1. Significant correlation was observed between concentrations of Ni in umbilical cord and methylation level of ZEB1. The hypermethylation of ZEB1 had a mediating effect by 20.47 % of total effect of Ni on NSOFC risk. Hypermethylation of ZEB1 is associated with the risk for NSOFC and may partially explain the association between Ni exposure and NSOFC risk. Our findings provide new insights into the epigenetic mechanisms underlying NSOFC and suggesting potential targets for future therapeutic interventions.

Long‐lasting behavioral and neurochemical effects of early‐life environmental enrichment in rats submitted to neonatal morphine administration

AbstractThe present study examined the medium‐ and long‐term effects of early environmental enrichment (EE) on neuromotor, nociceptive, cognitive, behavioral, and neurochemical parameters in newborn rats repeatedly exposed to morphine. The study employed 90 Wistar rats: 10 adult nulliparous females and 80 male pups. Litter was split into standard and EE housing. Following, half of each litter received saline (S) or morphine (M) injections, resulting in four groups: SC + S, EE + S, SC + M, and EE + M. EE was applied from PND1 to PND21, while morphine or saline was given daily (5 μg/s.c.) from PND8 to PND14. Neuromotor development was similar between groups. In the OF test, morphine reduced outer and total crossings, whereas EE increased inner crossings and rearings. Adult rats showed a decrease in outer and total crossings and grooming and an increase in rearing. EE increased the number of protected and unprotected head dipping. Adult rats showed an increase in protected head dipping. Adult rats showed a lower recognition index, and, when exposed to EE, a lower anxiety index and analgesia. EE increased brainstem and hippocampal BDNF levels. Adult rats had increased hypothalamus, spinal cord, and brainstem BDNF levels, an increase in the spinal cord, and decreased hypothalamus TNF‐α levels. This study demonstrated that early‐life EE raises BDNF levels in the brainstem and hippocampus of rats and modifies their behaviors (such as nociception, exploration, and anxiety) in a state‐dependent manner (morphine and age).

"Mitotic" kinesin-5 is a dynamic brake for axonal growth.

During neuronal development, neurons undergo significant microtubule reorganization to shape axons and dendrites, establishing the framework for efficient wiring of the nervous system. Previous studies from our laboratory demonstrated the key role of kinesin-1 in driving microtubule-microtubule sliding, which provides the mechanical forces necessary for early axon outgrowth and regeneration in Drosophila melanogaster. In this study, we reveal the critical role of kinesin-5, a mitotic motor, in modulating the development of postmitotic neurons. Kinesin-5, a conserved homotetrameric motor, typically functions in mitosis by sliding antiparallel microtubules apart in the spindle. Here, we demonstrate that the Drosophila kinesin-5 homolog, Klp61F, is expressed in larval brain neurons, with high levels in ventral nerve cord (VNC) neurons. Knockdown of Klp61F using a pan-neuronal driver leads to severe locomotion defects and complete lethality in adult flies, mainly due to the absence of kinesin-5 in VNC motor neurons during early larval development. Klp61F depletion results in significant axon growth defects, both in cultured and in vivo neurons. By imaging individual microtubules, we observe a significant increase in microtubule motility, and excessive penetration of microtubules into the axon growth cone in Klp61F-depleted neurons. Adult lethality and axon growth defects are fully rescued by a chimeric human-Drosophila kinesin-5 motor, which accumulates at the axon tips, suggesting a conserved role of kinesin-5 in neuronal development. Altogether, our findings show that at the growth cone, kinesin-5 acts as a brake on kinesin-1-driven microtubule sliding, preventing premature microtubule entry into the growth cone. This regulatory role of kinesin-5 is essential for precise axon pathfinding during nervous system development.

The association between macrosomia and glucose, lipids and hormones levels in maternal and cord serum: a case-control study

BackgroundThe formation of macrosomia is associated with excessive nutrition and/or unable to regulate effectively. This case-control study aims to explore the relationship between macrosomia and glucose, lipids and hormones levels in maternal and cord serum.MethodsIn the case-control study, 78 pairs of mothers and newborns were recruited who received care at one hospital of Hebei, China between 2016 and 2019. According to the birth weight (BW) of newborns, participants were divided into macrosomia group (BW ≥ 4000 g, n = 39) and control group (BW between 2500 g and 3999 g, n = 39). Maternal vein blood and cord vein blood were collected and assayed. All data were compared between the two groups. Unconditional logistics regression analysis was used to test the relationship between macrosomia and glucose, lipids and hormones in maternal and cord serum.ResultsIn maternal and cord serum, the levels of leptin, leptin/adiponectin ratio (LAR), glucose and triglyceride (TG) in macrosomia group were higher than those in control group, and the levels of high-density lipoprotein cholesterol (HDL-C) were lower. The percentage of maternal glucose and lipids transfer to cord blood did not differ between the two groups. High levels of TG in maternal serum were positively correlated with macrosomia, and high levels of LAR, TG and glucose in cord serum were positively correlated with macrosomia.ConclusionIn conclusion, the results of the current study, suggest that the nutrients and metabolism-related hormones in maternal and umbilical cord are closely related to macrosomia. During pregnancy, the nutritional status of pregnant women should be paid attention to and to obtain a good birth outcome.

Expression of Macrophage Colony-Stimulating Factor CSF-1 in Spinal Cord Neurons in Mice with Experimental Autoimmune Encephalomyelitis.

In mice with acute and chronic models of experimental autoimmune encephalomyelitis (EAE), a quantitative study of the dynamics of CSF-1 and IL-34 protein levels in the spinal cord and blood plasma was conducted by ELISA and the specificity of CSF-1 expression in spinal cord cells was examined by immunohistological methods. A significant increase in the level of CSF-1 in the spinal cord was detected and populations of motoneurons with intense CSF-1 immunoreactivity were identified in mice with acute and chronic EAE. The obtained results suggest a possible role of CSF-1 in the pathogenesis and progression of EAE/multiple sclerosis.

Anandamide-Mediated Modulation of Nociceptive Transmission at the Spinal Cord Level.

Three decades ago, the first endocannabinoid, anandamide (AEA), was identified, and its analgesic effect was recognized in humans and preclinical models. However, clinical trial failures pointed out the complexity of the AEA-induced analgesia. The first synapses in the superficial laminae of the spinal cord dorsal horn represent an important modulatory site in nociceptive transmission and subsequent pain perception. The glutamatergic synaptic transmission at these synapses is strongly modulated by two primary AEA-activated receptors, cannabinoid receptor 1 (CB1) and transient receptor potential vanilloid 1 (TRPV1), both highly expressed on the presynaptic side formed by the endings of primary nociceptive neurons. Activation of these receptors can have predominantly inhibitory (CB1) and excitatory (TRPV1) effects that are further modulated under pathological conditions. In addition, dual AEA-mediated signaling and action may occur in primary sensory neurons and dorsal horn synapses. AEA application causes balanced inhibition and excitation of primary afferent synaptic input on superficial dorsal horn neurons in normal conditions, whereas peripheral inflammation promotes AEA-mediated inhibition. This review focuses mainly on the modulation of synaptic transmission at the spinal cord level and signaling in primary nociceptive neurons by AEA via CB1 and TRPV1 receptors. Furthermore, the spinal analgesic effect in preclinical studies and clinical aspects of AEA-mediated analgesia are considered.

Morphometric analysis of spinal motor neuron degeneration in sporadic amyotrophic lateral sclerosis

ObjectivesThis study aimed to clarify the relationship between 43-kDa TAR DNA-binding protein (TDP-43) pathology and spinal cord anterior horn motor neuron (AHMN) atrophy in sporadic amyotrophic lateral sclerosis (SALS). MethodsEight patients with SALS and 12 controls were included in this study. Formalin-fixed specimens of lumbar spinal cord samples were paraffin-embedded and sectioned at the level of the fourth lumbar spinal cord with a 4 μm thickness. Using a microscope, the long diameters of the neurons with nucleoli were measured in spinal AHMNs stained with an anti-SMI-32 antibody. AHMNs were divided into medial and lateral nuclei for statistical analysis. We also used previously reported data to measure the long diameter of AHMNs with initial TDP-43 pathology, in which TDP-43 was present both in the nucleus and cytoplasm. ResultsThe long diameter of the lumbar spinal AHMNs in patients with SALS was smaller in the medial nucleus (42.54 ± 9.33 μm, n = 24) and the lateral nucleus (49.41 ± 13.86 μm, n = 129) than in controls (medial nucleus: 55.84 ± 13.49 μm, n = 85, p < 0.001; lateral nucleus: 62.39 ± 13.29 μm, n = 756, p < 0.001, Mann–Whitney U test). All 21 motor neurons with initial TDP-43 pathology were in the lateral nucleus, and their long diameter (67.60 ± 18.3 μm, p = 0.352) was not significantly different from that of controls. ConclusionMotor neuron atrophy in SALS does not occur during the initial stages of TDP-43 pathology, and TDP-43 pathology is already advanced in the atrophied motor neurons.

Hepatocyte Growth Factor Delivery to Injured Cervical Spinal Cord Using an Engineered Biomaterial Protects Respiratory Neural Circuitry and Preserves Functional Diaphragm Innervation.

A major portion of spinal cord injury (SCI) cases occur in the cervical region, where essential components of the respiratory neural circuitry are located. Phrenic motor neurons (PhMNs) housed at cervical spinal cord level C3-C5 directly innervate the diaphragm, and SCI-induced damage to these cells severely impairs respiratory function. In this study, we tested a biomaterial-based approach aimed at preserving this critical phrenic motor circuitry after cervical SCI by locally delivering hepatocyte growth factor (HGF). HGF is a potent mitogen that promotes survival, proliferation, migration, repair, and regeneration of a number of different cell and tissue types in response to injury. We developed a hydrogel-based HGF delivery system that can be injected into the intrathecal space for local delivery of high levels of HGF without damaging the spinal cord. Implantation of HGF hydrogel after unilateral C5 contusion-type SCI in rats preserved diaphragm function, as assessed by invivo recordings of both compound muscle action potentials and inspiratory electromyography amplitudes. HGF hydrogel also preserved PhMN innervation of the diaphragm, as assessed by both retrograde PhMN tracing and detailed neuromuscular junction morphological analysis. Furthermore, HGF hydrogel significantly decreased lesion size and degeneration of cervical motor neuron cell bodies, as well as reduced levels surrounding the injury site of scar-associated chondroitin sulfate proteoglycan molecules that limit axon growth capacity. Our findings demonstrate that local biomaterial-based delivery of HGF hydrogel to injured cervical spinal cord is an effective strategy for preserving respiratory circuitry and diaphragm function.

Atlas-guided brain projection tracts: From regions of interest to tractography 3D rendering.

The use of diffusion tensor imaging (DTI) has seen significant development over the last two decades, in particular with the development of the tractography of association tracts for preoperative planning of surgery. However, projection tracts are difficult to differentiate from one another and tractography studies have failed to reconstruct these ascending/descending pathways from/to the spinal cord. The present study proposes an atlas of regions of interest (ROIs) designed specifically for projection tracts tractography. Forty-nine healthy subjects were included in this prospective study. Brain DTI was acquired using the same 3 T MRI scanner, with 32 diffusion directions. Distortions were corrected using the FSL software package. ROIs were drawn using the anterior commissure (AC)-posterior commissure (PC) line on the following landmarks: the pyramid for the corticospinal tract, the medio-caudal part of the red nucleus for the rubrospinal tract, the pontine reticular nucleus for corticoreticular tract, the superior and inferior cerebellar peduncles for, respectively, the anterior and posterior spinocerebellar tract, the gracilis and cuneatus nucleus for the dorsal columns, and the ventro-posterolateral nucleus for the spinothalamic tract. Fiber tracking was performed using a deterministic algorithm using DSI Studio software. ROI coordinates, according to AC-PC line, were given for each tract. Tractography was obtained for each tract, allowing tridimensional rendering and comparison of tracking metrics between tracts. The present study reports the accurate design of specific ROIs for tractography of each projection tract. This could be a useful tool in order to differentiate projection tracts at the spinal cord level.

Immediate vs delayed venous thromboembolism prophylaxis following spine surgery: increased rate of unplanned reoperation for postoperative hematoma with immediate prophylaxis

BACKGROUND CONTEXTThere is significant variability in postoperative chemoprophylaxis protocols amongst spine providers due to perceived risks and benefits, but limited data on the topic. At our institution, both orthopaedic spine and neurosurgery departments utilize unfractionated subcutaneous heparin in identical dosages and frequency, with the only difference being time to initiation postoperatively. PURPOSETo evaluate the rate of symptomatic venous thromboembolism (VTEs) and unplanned reoperation for hematoma based on timing of chemoprophylaxis initiation. STUDY DESIGN/SETTINGSingle institution retrospective cohort study. PATIENT SAMPLEPatients undergoing elective spine surgery, excluding patients undergoing surgery in the setting of trauma, malignancy, or infection. OUTCOME MEASURESOutcome measures included the diagnosis of a venous thromboembolism within 90 days of surgery and unplanned reoperation for a hematoma. METHODSPatients undergoing elective spine surgery from 2017 to 2021 were grouped based on chemoprophylaxis protocol. In the “immediate” group, patients received subcutaneous heparin 5000 units every 8 hours starting immediately after surgery, and in the “delayed” group, patients received chemoprophylaxis starting postoperative day (POD)-2 for any decompressions and/or fusions involving a spinal cord level (ie, L2 and above) and POD-1 for those involving only levels below the spinal cord (ie, L3 to pelvis). A cox proportional hazards model was created to assess independent predictors of venous thromboembolic events, while a logistic regression was utilized for unplanned reoperations for hematoma. RESULTSOf 8,704 patients, a total of 98 (1.13%) VTE events occurred, of which 43 (0.49%) were pulmonary embolism. Fifty-four patients (0.62%) had unplanned reoperations for postoperative hematomas. On cox proportional hazards model analysis, immediate chemoprophylaxis was not protective of a venous thromboembolism (Hazard Ratio: 1.18, p=.436), but, it was a significant independent predictor for unplanned reoperation for hematoma on multivariable logistic regression modeling (Odds Ratio: 3.29, p<.001). CONCLUSIONSBoth chemoprophylaxis protocols in our study resulted in low rates of VTE and postoperative hematoma. However, our findings suggest that the delayed chemoprophylaxis protocol may mitigate postoperative hematoma formation without increasing the risk for a thrombotic event.

Neuro-microcirculatory interrelationships in patients with kyphoscoliosis associated with neurological deficits

Background: The use of laser Doppler flowmetry with spectral wavelet analysis of blood flow fluctuations allows us to assess the functional state of thin unmyelinated nerve fibers and objectify the dynamics of recovery processes in patients with kyphoscoliotic spinal deformities associated with spinal cord compression. AIM: To study the features of neuromicrocirculatory relationships in patients with kyphoscoliosis associated with neurological deficits before and after surgical treatment. MATERIALS AND METHODS: 20 patients with spinal deformities associated with neurological deficits of varying severity were examined using the LDF method and operated on. Patients were examined before surgery, 1–2 weeks after surgery following regression of acute postoperative pain syndrome, 3–6 months, 6–12 months, and more than a year after surgery. The scope of the study included a general examination with a detailed assessment of the neurological status, radiation diagnostics (postural radiographs of the spine, computed tomography and magnetic resonance imaging of the spine with assessment of spinal canal stenosis). Patients with severe kyphoscoliotic deformities underwent CT myelography followed by the design of individual full-size 3D plastic models of the spine and myeloradicular structures. LDF with wavelet analysis was carried out at all periods of the survey. A perfusion study with determination of the average microcirculation was carried out at the level of the pad of the distal phalanx of the big toe using a two-channel LAKK-02 device with a semiconductor laser (sensing in the red Raman and infrared IR channels). The obtained LDF results were processed by spectral amplitude-frequency wavelet analysis to characterize microcirculation regulation factors in the ranges of sympathetic adrenergic regulation (0.02–0.046 Hz), sensory peptidergic influences (0.047–0.069 Hz), myogenic oscillations (0.07–0.145 Hz). RESULTS: After surgery, the activity of trophotropic sensory peptidergic nerve fibers, the values of perfusion of the microcirculatory channel increased and was maintained starting from the early postoperative period. Ergotropic sympathetic adrenergic activity was significantly decreased in the period of 6-12 months after surgery. Maximum mobilization of trophotropic neurogenic mechanisms of sanogenesis was observed in the period of 6-12 months after surgery. CONCLUSION: The obtained data indicate a significant participation of thin nerve fibers in the recovery processes after decompressive surgeries in the spinal canal zone and the creation of anatomical conditions for neurophysiological repair at the spinal cord level. The use of the LDF method with spectral wavelet analysis of blood flow fluctuations makes it possible to objectify the dynamics of thin unmyelinated nerve fibers and recovery processes in patients with kyphoscoliotic deformities of the spine associated with spinal cord compression.

Predictors of unfavorable neurological outcomes in premature children: a modern view on the problem

Objective: to assess the prognostic significance of antibodies to the NR2 subunit of the N-methyl-D-aspartate (NMDA) glutamate receptor and brain natriuretic propeptide (NTproBNP) as predictors of unfavorable neurological outcomes in premature children.Materials and methods: A prospective cohort continuous study included 151 premature children, with a gestational age (GA) of 26–32 weeks and a body weight of 590–1990 gr. The children were measured the quantitation of NTproBNP level in the cord blood and level of antibodies to the NR2 subunit of the N-methyl-D-aspartate (NMDA) glutamate receptor in the blood serum on the 21st day of life. The division of children into groups was carried out in accordance with the assessment of neurological outcomes at control points of the research: 1 control point — at the time of discharge from the hospital, 2 control point — at the age of 1 year of corrected age (CA), 3 control point — 4 years of life.Results: in the course of the study, it was found a “cascade” increase in the cohort of children with unfavorable neurological outcomes from 36.4% at the time of discharge from the hospital to 70% by the age of 4 years. High values of NT-proBNP level in cord blood and antibodies to the NR2 subunit of the N-methyl-D-aspartate (NMDA) glutamate receptor were established on 21st day of postnatal life in children with both macrostructural brain damages in the neonatal period and having an unfavorable neurological outcome at the age of 1 year of corrected age (CA) and at 4 years of life.Conclusion: modern neurochemical markers of CNS damages N-proBNP and antibodies to the NR2 subunit of the N-methyl-D-aspartate (NMDA) glutamate receptor open up the possibilities of early diagnosis of brain damages at the cellular level and the start of neuroprotective therapy to reduce neurological disability.

Mechanisms and risk factors associated with spinal cord injury, facet fracture, and level of dislocation, in occupants with cervical spine dislocations sustained in motor vehicle crashes

Objective Motor vehicle crashes (MVCs) are the leading cause of cervical spine dislocation. The mechanisms underlying this injury are unclear, limiting the development of injury prevention devices and strategies. MVC databases contain occupant, medical, vehicle, and crash details that are not routinely collected elsewhere, providing a unique resource for investigating injury mechanisms and risk factors. In this study, a comprehensive standalone analysis of cervical spine dislocations captured in MVC databases was performed. Methods Epidemiologic, biomechanical, and injury data were extracted from three MVC databases. Logistic regression models were developed to determine the occupant, vehicle, and crash characteristics, as well as the global (inertial or impact) and regional (flexion, compression, etc.) loading mechanisms associated with the level of cervical spine dislocation (axial or sub-axial), and the occurrence of spinal cord injury (SCI) or facet fracture concomitant to dislocation. Results There was no association between global or regional injury mechanisms and the level of cervical spine dislocation. Sub-axial dislocations were typically due to head/face impact with the airbag or upper interior components, or a result of seatbelt restraint of the torso. Higher occupant age, lower BMI, partial/no ejection, and frontal and side configuration crashes (compared to rollovers) were associated with a higher likelihood of sub-axial, versus axial, dislocation. Amongst all dislocations, an increased likelihood of SCI was associated with impact injuries, airbag non-deployment, and complete ejection, while concomitant facet fracture was associated with the presence of regional compression. Severe crashes, partial ejections, and “utility vehicles” and “vans and trucks” (compared with “passenger vehicles”) were associated with a higher risk of facet fracture concomitant to sub-axial dislocation. Conclusion The findings of this study may be used to inform the loading modes to be simulated in future ex vivo or computational models seeking a better understanding of cervical spine dislocations.