Low Thoracic Spinal Cord Injury Research Articles

Spectral Analyses of Cardiovascular Control in Rodents with Spinal Cord Injury

The severity of injury to cardiovascular autonomic pathways following clinical spinal cord injury (SCI) can be evaluated with spectral analyses. Whether this technique provides a translatable assessment of cardiovascular autonomic function in rodent SCI is unknown. Beat-to-beat blood pressure and pulse interval were measured in male rats 1 month after complete T3 or T10 SCI, and in uninjured control animals. Univariate autoregressive spectral analyses were performed and the power of the low frequency (LF), high frequency (HF), and very low frequency (VLF) peaks identified. Frequency domain variables were correlated with the severity of orthostatic hypotension (OH) and the severity of hypertension during autonomic dysreflexia (AD). Total heart rate variability (HRV) and blood pressure variability (BPV) were reduced in animals with T3, but not T10, SCI. VLF and LF HRV were reduced and HF HRV was increased in animals with T3 SCI compared to controls; there were no changes in animals with T10 SCI. BPV in the VLF and LF range was reduced in animals with T3 SCI, but not T10 SCI. In all animals with SCI, severity of OH was positively correlated with LF BPV, and negatively correlated with HF BPV. Severity of AD was positively correlated with HF BPV and HF HRV, and negatively correlated with VLF HRV. Spectral analyses can detect alterations in cardiovascular autonomic function in animals with SCI at rest. These parameters underscore the distinct cardiovascular ramifications of high- versus low-thoracic SCI, and correlate with the severity of AD and OH, clinically-relevant measures of abnormal blood pressure control.

Plasticity of TRPV1-Expressing Sensory Neurons Mediating Autonomic Dysreflexia Following Spinal Cord Injury

Spinal cord injury (SCI) triggers profound changes in visceral and somatic targets of sensory neurons below the level of injury. Despite this, little is known about the influence of injury to the spinal cord on sensory ganglia. One of the defining characteristics of sensory neurons is the size of their cell body: for example, nociceptors are smaller in size than mechanoreceptors or proprioceptors. In these experiments, we first used a comprehensive immunohistochemical approach to characterize the size distribution of sensory neurons after high- and low-thoracic SCI. Male Wistar rats (300 g) received a spinal cord transection (T3 or T10) or sham-injury. At 30 days post-injury, dorsal root ganglia (DRGs) and spinal cords were harvested and analyzed immunohistochemically. In a wide survey of primary afferents, only those expressing the capsaicin receptor (TRPV1) exhibited somal hypertrophy after T3 SCI. Hypertrophy only occurred caudal to SCI and was pronounced in ganglia far distal to SCI (i.e., in L4-S1 DRGs). Injury-induced hypertrophy was accompanied by a small expansion of central territory in the lumbar spinal dorsal horn and by evidence of TRPV1 upregulation. Importantly, hypertrophy of TRPV1-positive neurons was modest after T10 SCI. Given the specific effects of T3 SCI on TRPV1-positive afferents, we hypothesized that these afferents contribute to autonomic dysreflexia (AD). Rats with T3 SCI received vehicle or capsaicin via intrathecal injection at 2 or 28 days post-SCI; at 30 days, AD was assessed by recording intra-arterial blood pressure during colo-rectal distension (CRD). In both groups of capsaicin-treated animals, the severity of AD was dramatically reduced. While AD is multi-factorial in origin, TRPV1-positive afferents are clearly involved in AD elicited by CRD. These findings implicate TRPV1-positive afferents in the initiation of AD and suggest that TRPV1 may be a therapeutic target for amelioration or prevention of AD after high SCI.

Influence of bone marrow mesenchymal stem cells transplantation on the expression of AMPA receptor protein in rats with spinal cord injury

Objective To observe the influence of bone marrow mesenchymal stem cells (BMSCs) transplantation on the expression of alpha-amino hydroxymethyl-oxazole propionic acid (AMPA) receptors GluR1 and GluR2 in rats with spinal cord injury (SCI) so as to investigate the potential anti- chronic stress mechanism of BMSCs transplantation in treatment of rats with spinal cord injury.Methods A total of 48 adult male SD rats were equally divided into three groups:control group,treatment group and model group.The rats in the model and treatment group underwent lower thoracic SCI with the modified Allen' s method,and the rats in control group received only laminectomy.At day 7 after thoracic SCI,100 μl of Hank's buffered saline solution containing 1.0 × 106 BMSCs was injected into the subarachnoid space from L4-L5 intervertebral space in the treatment group and control group,and the same amount of Hank' s buffered saline solution was injected in the model group.The motor function of the rat posterior limbs was assessed by Basso-Beattie-Bresnahan (BBB) scale before and after operation.Half of the rats were anesthetized at days 14 and 28 postoperatively to harvest brains which were frozen and cut in a cryostat to detect the expressions of GluR1 and GluR2 proteins by immunohistochemistry.Results After BMSCs transplantation,the motor function of the posterior limbs in the treatment group was improved progressively.At day 14 after transplantation,the number of GluR1-positive cells of the model and treatment group was higher than that of the control group in the hippocampus CA1 region (P ＜0.05,P ＜0.01 respectively) ; GluR2-positive cells had the similar tendency,without significant difference(P ＞ 0.05 ).At the 28th day after transplantation,GluR1 positive cells of the model group were higher than those of the control group in CA1,CA3,DG regions and those of the treatment group in CA1,CA3 regions (P ＜0.05,P ＜0.01,respectively) ; GluR1 positive cells of the model and treatment group were higher than their counterpart at day 14 after grafting procedure,with significant difference (P ＜0.05,P ＜0.01,respectively).GluR2 positive cells of the treatment group were higher than those of the control group in the basolateral amygdale (BLA) (P ＜0.05 ) and had similar tendency with GluR1 expression in other regions ( P ＞ 0.05 ).Conclusion BMSCs transplantation implies a potential antichronic stress mechanism of SCI rats,since it can improve the motor function of posterior limbs in rats with lower thoracic SCI and regulate the expressions of AMPA receptor GluR1 and GluR2. Key words: Spinal cord injury; Bone mesenchymal stem cells; Receptoos, glutamate

296 Spectral analysis of cardiovascular control after spinal cord injury in rats: Effect of time post-injury

296 Spectral analysis of cardiovascular control after spinal cord injury in rats: Effect of time post-injury

Characterization of neurological recovery following traumatic sensorimotor complete thoracic spinal cord injury

Retrospective, longitudinal analysis of sensory, motor and functional outcomes from individuals with thoracic (T2-T12) sensorimotor complete spinal cord injury (SCI). To characterize neurological changes over the first year after traumatic thoracic sensorimotor complete SCI. A dataset of 399 thoracic complete SCI subjects from the European Multi-center study about SCI (EMSCI) was examined for neurological level, sensory levels and sensory scores (pin-prick and light touch), lower extremity motor score (LEMS), ASIA Impairment Scale (AIS) grade, and Spinal Cord Independence Measure (SCIM) over the first year after SCI. AIS grade conversions were limited. Sensory scores exhibited minimal mean change, but high variability in both rostral and caudal directions. Pin-prick and light touch sensory levels, as well as neurological level, exhibited minor changes (improvement or deterioration), but most subjects remained within one segment of their initial injury level after 1 year. Recovery of LEMS occurred predominantly in subjects with low thoracic SCI. The sensory zone of partial preservation (ZPP) had no prognostic value for subsequent recovery of sensory levels or LEMS. However, after mid or low thoracic SCI, ≥3 segments of sensory ZPP correlated with an increased likelihood for AIS grade conversion. The data suggest that a sustained deterioration of three or more thoracic sensory levels or loss of upper extremity motor function are rare events and may be useful for tracking the safety of a therapeutic intervention in early phase acute SCI clinical trials, if a significant proportion of study subjects exhibit such an ascent.

Care of Rats with Complete High-Thoracic Spinal Cord Injury

The complications of spinal cord injury (SCI) increase in number and severity with the level of injury. A recent survey of SCI researchers reveals that animal models of high SCI are essential. Despite this consensus, most laboratories continue to work with mid- or low-thoracic SCI. The available data on cervical SCI in animals characterize incomplete injuries; for example, nearly all studies published in 2009 examine discrete, tract-specific lesions that are not clinically-relevant. A primary barrier to developing animal models of severe, higher SCI is the challenge of animal care, a critical determinant of experimental outcome. Currently, many of these practices vary substantially between laboratories, and are passed down anecdotally within institutions. The care of animals with SCI is complex, and becomes much more challenging as the lesion level ascends. In our experience, the care of animals with high-thoracic (T3) SCI is much more demanding than the care of animals with low-thoracic SCI, even though both injuries result in paraplegia. We have developed an animal care regimen for rats with complete high-thoracic SCI. Our practices have been refined over the past 7 years, in collaboration with animal care centre staff and veterinarians. During this time, we have cared for more than 300 rats with T3 complete transection SCI, with experimental end-points of up to 3 months. Here we provide details of our animal care procedures, including acclimatization, housing, diet, antibiotic prophylaxis, surgical procedures, post-operative monitoring, and prevention of complications. In our laboratory, this comprehensive approach consistently produces good outcomes following T3 complete transection SCI: using body weight as an objective indicator of animal health, we have found that our rats typically return to pre-operative weights within 10 days of T3 complete SCI. It is our hope that the information provided here will improve care of experimental animals, and facilitate adoption of models that directly address the complications associated with higher level injuries.

Cardiometabolic Risk Factors in Experimental Spinal Cord Injury

Cardiometabolic risk factors are sorely underreported after spinal cord injury (SCI), despite the high prevalence of metabolic disorders and cardiovascular mortality in this population. Body-composition analysis and serum-lipid profiling are two assessments that are beginning to be more widely used to document metabolic changes after clinical SCI. Individuals with SCI have been reported to carry increased visceral fat and to exhibit altered serum-lipid levels. However, little is known about the development of these cardiometabolic risk factors in animal models. Using a combination of magnetic resonance imaging (MRI) and adipose tissue dissection, we show that visceral and subcutaneous adipose tissue were both increased at 1 month, but not at 1 week, after complete T3 SCI in rats. Additionally, at 1 month post injury, T3 SCI rats exhibited nonfasting serum hypertriglyceridemia, a result obtained using both standard clinical methods and a home cholesterol monitoring device (CardioChek). Interestingly, at 1 month post injury, rats with complete T10 SCI did not show an increase in either visceral adiposity or serum triglyceride levels. The fact that complete high-thoracic SCI disrupts lipid metabolism and perturbs fat storage in the subacute period, while low-thoracic SCI does not, suggests that differences in descending sympathetic control of adipose tissue might play a role in these changes. These results provide the first evidence of cardiometabolic risk factors in experimental animals with SCI, and are a starting point for investigations of the etiology of obesity and metabolic dysfunctions that often accompany SCI.

Involuntary, Electrically Excitable Nerve Transfer for Denervation: Results From an Animal Model

The purpose of this study was to evaluate the efficacy of "paralyzed" nerve transfer (ie, transfer of an involuntary, nondegenerated, electrically excitable nerve onto an involuntary, degenerated, non-electrically excitable nerve) and functional electrical stimulation for reinnervation. We hypothesized that lower motor neuron cell body continuity with the motor cortex, via intact upper motor neurons, is not necessary for reinnervation of the extremities. Fischer 344 rats had lower thoracic spinal cord injury (SCI) followed by unilateral tibial nerve transection and delayed peroneal ("paralyzed") to tibial nerve transfer (group A) or primary neurorrhaphy (group B). Control groups had SCI and a unilateral hindlimb incision and nerve exposure only (group C) or a unilateral hindlimb disection and transection of both the tibial and peroneal nerves (group D). Three months after surgery, the proximal peroneal (group A) or proximal tibial (groups B, C, and D) nerves were electrically stimulated in vivo, and gastrocnemius force production was measured on both the operative and nonoperative hindlimbs. In addition, the distal tibial nerves from both the experimental and control-side hindlimbs were sectioned and stained with anti-neurofilament protein to determine total axon counts. Mean gastrocnemius force return and mean axonal regeneration was 47% and 51%, respectively, for group A animals (n = 9), 68% and 73% for group B animals (n = 4), 97% and 99% for group C animals (n = 4), and 0 and 2% for group D animals (n = 4). A 1-way analysis of variance for independent samples yielded significant differences between groups A, B, and C for gastrocnemius force return and between all groups for axonal regeneration. Paralyzed nerve transfer produces a mean of approximately 50% return of gastrocnemius force and axonal regeneration. Paralyzed nerve transfer combined with functional electrical stimulation is a viable method for reanimating denervated motor units in the setting of SCI.

Intrathecal glutamate promotes glycinergic neuronal activity and inhibits the micturition reflex in urethane‐anesthetized rats

In order to clarify the role of glutamate in the micturition reflex and in glutamatergic and glycinergic neuronal activity, we examined the effects of intrathecal (IT) injection of glutamate or MK-801 (an N-methyl-D-aspartate receptor antagonist) on bladder activity and on the glutamate and glycine levels in the lumbosacral cord of female rats with or without acute lower thoracic spinal cord injury (SCI). Under urethane anesthesia, isovolumetric cystometry was performed in rats with or without SCI before and after IT injection of glutamate or MK-801 at the lumbosacral cord level. The glutamate and glycine levels of the whole lumbosacral cord were measured after IT injection of glutamate or MK-801 in both groups. In intact rats, IT glutamate (100 microg) prolonged the interval between bladder contractions and decreased the amplitude of contractions. IT MK-801 (3-100 microg) also prolonged the interval between bladder contractions and decreased the amplitude in intact rats. In SCI rats, cystometry demonstrated the disappearance of bladder contractions, and the glycine level in the lumbosacral cord was elevated. In intact rats, IT glutamate (0.3-100 microg) increased the glycine level in the lumbosacral cord. On the other hand, IT MK-801 (3-100 microg) decreased both glutamate and glycine levels in intact and SCI rats. These results suggest that glutamatergic neurons have stimulatory projections to both glutamatergic and glycinergic neurons in the lumbosacral cord, and that glutamatergic neurons inhibit the micturition reflex by stimulating glycinergic neurons.

Respiratory Complications and Mortality Risk Associated with Thoracic Spine Injury

Cervical spinal cord injury (SCI) has a well-established association with a high risk of respiratory complications. We sought to determine whether high-thoracic (HT) SCI was associated with a similar increased risk of respiratory complications and death. This was a retrospective cohort study of all adult patients with thoracolumbar injuries entered into the Pennsylvania Trauma System Foundation registry between January 1993 and December 2002. Records were reviewed for the documentation of respiratory complications (intubation, tracheostomy, bronchoscopy, pneumonia) and mortality. The data were then evaluated controlling for age, sex, Glasgow Coma Scale, and Injury Severity Score. In all, 11,080 patients met inclusion criteria: 4,258 patients had thoracic spine fractures and 6,226 patients had lumbar spine fractures, all without SCI; and 596 patients had thoracic SCI (T1 to T6, 231; T7 to T12, 365). Respiratory complications occurred in 51.1% of patients with T1 to T6 SCI (versus 34.5% in T7 to T12 SCI and 27.5% in thoracic fractures). The need for intubation, the risk of pneumonia, and risk of death were significantly greater for patients with T1- to T6-level spinal cord injuries. Among patients with an Injury Severity Score less than 17 (n = 6427), the relative mortality risk was 26.7 times higher among those who developed respiratory complications (9.9% versus 0.4%). Compared with patients with low thoracic SCI or thoracolumbar fractures, patients with HT-SCI have an increased risk of pneumonia and death. Respiratory complications significantly increase the mortality risk in less severely injured patients. The current findings suggest that HT-SCI patients warrant intensive monitoring and aggressive pulmonary care and attention, similar to that given for patients with cervical SCI.

INTRATHECAL OR DIETARY GLYCINE INHIBITS BLADDER AND URETHRAL ACTIVITY IN RATS WITH SPINAL CORD INJURY

We examined the influence of intrathecal or dietary glycine on bladder and urethral activity in rats with spinal cord injury. A total of 20 female Sprague-Dawley rats were used 4 weeks after lower thoracic spinal cord injury. The rats were divided into standard and 1% glycine diet groups. In the standard diet group isovolumetric cystometry and urethral pressure measurement were performed before and after intrathecal injection of glycine. In the 1% glycine diet group bladder and urethral activity were compared with control recordings in the standard diet group. In the standard diet group intrathecal injection of glycine prolonged the interval and decreased the amplitude of bladder contractions, decreased baseline urethral pressure and altered urethral activity during bladder contraction from a pattern of detrusor-sphincter dyssynergia to detrusor-sphincter synergy at 100 mug glycine. In the 1% glycine diet group the interval and amplitude of bladder contractions were prolonged and decreased, respectively, compared with those in the standard diet group. Baseline urethral pressure was lower than in the standard diet group even after intrathecal injection of 100 mug glycine. Urethral pressure did not change during bladder contraction and it was the same as baseline pressure. Residual urine volume was lower than in the standard diet group. Intrathecal or dietary glycine inhibits bladder and urethral activity, and improves detrusor hyperreflexia and detrusor-sphincter dyssynergia.

Poster 211: Determination of the Neurologic Level Using Abdominal Electromyography in Lower Thoracic Spinal Cord Injury

Poster 211: Determination of the Neurologic Level Using Abdominal Electromyography in Lower Thoracic Spinal Cord Injury

The relationship between sitting stability and functional performance in patients with paraplegia

Chen C-L, Yeung K-T, Bih L-I, Wang C-H, Chen M-I, Chien J-C. The relationship between sitting stability and functional performance in patients with paraplegia. Arch Phys Med Rehabil 2003;84:1276–81 Objectives: To compare sitting stability between patients with high and low thoracic spinal cord injury (SCI), to determine the factors that can predict sitting stability, and to examine the relationship between sitting stability and functional performance. Design: Cross-sectional assessment was performed on subjects with paraplegia. Setting: Rehabilitation hospital affiliated with a medical university. Participants: Convenience sample of 30 adults with complete chronic thoracic SCI. Interventions: Not applicable. Main Outcome Measures: (1) Postural sway during quiet sitting over 30 seconds was recorded as static sitting stability, and composite maximal weight-shift during leaning tasks over 30 seconds was measured as dynamic sitting stability; (2) age, body weight, trunk length, trunk strength, postonset duration, injury level, and presence of spasticity were examined as predictive variables for sitting stability; and (3) the time for completion of upper- and lower-body dressing and undressing and transfer was measured as functional performance. Results: A significant difference in composite maximal weight-shift was found between high and low thoracic SCI subjects ( t=2.90, P<.01). Injury level and trunk length were 2 important predictive factors for dynamic sitting stability, and they explained 43.5% of the variance. Only the completion time of upper-body dressing and undressing correlated significantly with static ( r=.465, P=.01) and dynamic ( r=−.377, P<.05) sitting stability. Conclusions: The subjects with low thoracic SCI showed better dynamic sitting stability than those with high thoracic SCI. Injury level and trunk length, not trunk flexion or extension strength, predicted the outcome of dynamic sitting stability. Measures were not precise enough to predict functional performance from the viewpoint of injury level and sitting stability. The underlying premise that a reduction or increase in trunk strength is indicative of poorer or better sitting stability in SCI individuals is questioned, and implications for problem identification and treatment planning are discussed.

Level of injury and hormone profiles in spinal cord-injured men

Objectives. To evaluate the level of injury and endocrine profiles in men with spinal cord injury (SCI). Methods. Seventy-six men with SCI at different levels were studied, using uninjured normal and infertile subjects as controls. Results. Compared with normal controls, the subjects with SCI (50%) had lower serum levels of luteinizing hormone, follicle-stimulating hormone, and testosterone. Subjects with T8-T11 and T12-L5 injury had the highest and lowest incidence of hormonal abnormalities, respectively. All subjects with hyperprolactinemia (n = 5) had T8-T11 injuries. Conclusions. The results of our study indicate that subjects with SCI have an altered central neurotransmitter tone, and the likelihood of these abnormalities (hypogonadotropism) are higher in men with low thoracic SCI.

The effect of seat tilting on pelvic position, balance control, and compensatory postural muscle use in paraplegic subjects

Janssen-Potten YJ, Seelen HA, Drukker J, Huson T, Drost MR. The effect of seat tilting on pelvic position, balance control, and compensatory postural muscle use in paraplegic subjects. Arch Phys Med Rehabil 2001;82:1393-402. Objective: To study the effect of seat tilting on pelvic tilt, balance control, and postural muscle use in persons with a thoracic spinal cord injury (SCI). Design: Cross-sectional group study. Setting: Rehabilitation centers and rehabilitation hospital departments. Patients: Ten complete high thoracic SCI (level T2-8) patients, 10 complete low thoracic SCI (level T9-12) patients, and 10 matched able-bodied controls. Intervention: A 10° forward inclination of the seat. Main Outcome Measures: Pelvic tilt, center of pressure displacement, and muscle activity. Results: Anterior tilting of the pelvis as a result of forward inclination of the seat could not be shown, either in persons with or without SCI. Balance control was not influenced by forward inclination of the seat. Participants' overall muscle activity decreased while they were seated in the chair with the forwardly inclined seat. Conclusions: Evidence provided by the kinematic and electromyographic data is not sufficient to develop a protocol for wheelchair prescription on the basis of pelvic positioning. © 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Regrowth of the Rostral Spinal Axons into the Caudal Ventral Roots through a Collagen Tube Implanted into Hemisected Adult Rat Spinal Cord

OBJECTIVE A collagen tube was used to guide axonal regrowth from the spinal cord to the periphery to contribute to improvement of paralysis after lower thoracic spinal cord injury. METHODS The spinal cords of adult male Sprague-Dawley rats were lesioned by removing the left hemicord from T12 to 5 mm below this level and additionally sectioning all left lumbar ventral roots. In experimental animals (n = 9), a collagen tube was inserted into this gap, spanning the rostral hemisected cord to the caudal sectioned lumbar ventral roots (gap, 7 mm). In control animals (n = 6), no treatment was performed. RESULTS Six months after surgery, the return of some tension and resistance of the paralyzed hindlimb muscles was observed in all experimental rats except the untreated controls. Nine months postoperatively, muscle action potentials were recorded from the target muscles of the experimental animals while electrostimulating the tissue continuity within the collagen tube. Horseradish peroxidase retrograde labeling showed that the neurons in the rostral cord near the implantation site regrew into the reconnected lumbar ventral roots. Histological examination indicated numerous myelinated axons in the reconnected root pathways and newly formed endplates in the target muscles. No axonal regeneration was found in the control rats. CONCLUSION These results indicate that the rostral spinal axons can regrow into the caudal sectioned and reconnected ventral roots through a collagen tube, thus innervating the denervated peripheral targets in adult rats after spinal cord injury. This surgical repair model also provides a means for testing the use of trophic factors that may further promote axonal regeneration.

Chair configuration and balance control in persons with spinal cord injury

Janssen-Potten YJM, Seelen HAM, Drukker J, Reulen JPH. Chair configuration and balance control in persons with spinal cord injury. Arch Phys Med Rehabil 2000;81:401-8. Objective: To study whether chair configuration influences sitting balance in persons with spinal cord injury (SCI). Design: Cross-sectional group study. Setting: Rehabilitation centers and hospital rehabilitation departments. Patients: Ten complete high thoracic SCI (level T2-T8) patients, 10 complete low thoracic SCI (T9-T12) patients, and 10 matched able-bodied controls. SCI participants had completed their active rehabilitation at least 6 months before the study. Interventions: A balance-changing (forward) reaching task while seated in four differently configured chairs. Tilt angle (7° and 12°) and reclination angle (22°) were varied relative to a standard chair configuration (10° reclination). Main Outcome Measures: Maximal unsupported reaching distance, center-of-pressure displacement and muscle activity. Results: Although no significant difference in actively controllable reach was found in controls or in subjects with low SCI, sitting balance improved in all chairs relative to the standard chair. Ability to control displacement of arms and trunk during reaching improved. No apparent need for additional postural muscle activity was found. Persons with high SCI did not improve their sitting balance. They were unable to control a shift in body mass larger than the one induced by arm movement. However, they had less muscle activity after backrest reclination or tilting the chair backwards. Conclusions: The tested chairs had an overall positive effect. However, for individually tailored chair configurations factors other than those investigated should be considered. © 2000 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Effects of High and Low Thoracic Spinal Cord Injury on the Oral Pharmacokinetics of Paracetamol in Rats

The pharmacokinetics of paracetamol were studied after oral administration to rats with two different levels of thoracic spinal cord injury (SCI), T1 and T8. Rats were subjected to SCI at T1 and T8 by compression and contusion methods, respectively, resulting in completed flaccid paraplegia, before administration of paracetamol (100 mg kg −1). The concentration of paracetamol in blood was increased in T1-injured rats (135±20 μg mL−1) and decreased in T8-injured rats (58±7 mg mL−1), compared with sham-lesioned controls (101±9 μg mL−1). The localization of SCI alters the pharmacokinetic parameters of paracetamol which may be due to effects on drug absorption and elimination.

Reinnervation of denervated lumbar ventral roots and their target muscle by thoracic spinal motoneurons via an implanted nerve autograft in adult rats after spinal cord injury

Intraspinally implanting a nerve autograft (NAG) to promote axonal regeneration toward periphery was investigated as a surgical treatment for spinal cord injury in adult rats. Fifteen animals underwent a left hemisection of the spinal cord at T12 level and an intradural section of all ipsilateral lumbar ventral roots. In repaired animals (n = 9), the electrophysiologically selected left L3 and L4 lumbar ventral roots supplying the quadriceps muscle were anastomosed to a NAG. The NAG was taken from the right peroneal nerve and then ventrolaterally implanted into the cord at a level 7 mm rostral to the hemisection. In the control group (n = 6), sectioned lumbar ventral roots were left unrepaired. Nine months later, the animals were assessed with clinical, electrophysiological, and histological examinations. Muscle action potential and motor evoked potential were obtained from the denervated/reinnervated quadriceps in all repaired animals, with a mean amplitude of 918.3 ± 328.9 μV and 215.8 ± 39.7 μV, respectively. Horseradish peroxidase retrograde labeling from the denervated/repaired lumbar ventral roots, performed in five repaired animals, showed that the mean of labeled neurons, ipsilaterally located in the thoracic ventral horn near the implantation site, was 145.8 ± 111.7. Histological analysis showed numerous myelinated axons in the NAG and denervated/repaired lumbar ventral roots of all repaired animals. The study of neuromuscular junctions furthermore confirmed numerous newly formed endplates appearing in the denervated/reinnervated quadriceps. These changes were absent in the control animals. These data indicate that the rostral thoracic spinal motoneurons can innervate the caudal denervated/repaired lumbar ventral roots and the target quadriceps via an implanted NAG, thereby inducing some functional recovery in adult rats after lower thoracic spinal cord injury. J. Neurosci. Res. 56:506–517, 1999. © 1999 Wiley-Liss, Inc.

Reinnervation of denervated lumbar ventral roots and their target muscle by thoracic spinal motoneurons via an implanted nerve autograft in adult rats after spinal cord injury.

Intraspinally implanting a nerve autograft (NAG) to promote axonal regeneration toward periphery was investigated as a surgical treatment for spinal cord injury in adult rats. Fifteen animals underwent a left hemisection of the spinal cord at T12 level and an intradural section of all ipsilateral lumbar ventral roots. In repaired animals (n = 9), the electrophysiologically selected left L3 and L4 lumbar ventral roots supplying the quadriceps muscle were anastomosed to a NAG. The NAG was taken from the right peroneal nerve and then ventrolaterally implanted into the cord at a level 7 mm rostral to the hemisection. In the control group (n = 6), sectioned lumbar ventral roots were left unrepaired. Nine months later, the animals were assessed with clinical, electrophysiological, and histological examinations. Muscle action potential and motor evoked potential were obtained from the denervated/reinnervated quadriceps in all repaired animals, with a mean amplitude of 918.3+/-328.9 microV and 215.8+/-39.7 microV, respectively. Horseradish peroxidase retrograde labeling from the denervated/repaired lumbar ventral roots, performed in five repaired animals, showed that the mean of labeled neurons, ipsilaterally located in the thoracic ventral horn near the implantation site, was 145.8+/-111.7. Histological analysis showed numerous myelinated axons in the NAG and denervated/repaired lumbar ventral roots of all repaired animals. The study of neuromuscular junctions furthermore confirmed numerous newly formed endplates appearing in the denervated/reinnervated quadriceps. These changes were absent in the control animals. These data indicate that the rostral thoracic spinal motoneurons can innervate the caudal denervated/repaired lumbar ventral roots and the target quadriceps via an implanted NAG, thereby inducing some functional recovery in adult rats after lower thoracic spinal cord injury.