Cholinergic receptor subtypes functional regulation in spinal cord injured monoplegic rats

The present study deals with the Cholinergic Receptor subtypes functional regulation in spinal cord injured monoplegic rats: Effect of 5-HT GABA and bone marrow cells.Spinal cord injury causes permanent and irrevocable motor deficits and neurodegeneration. Disruption of the spinal cord leads to diminished transmission of descending control from the brain to motor neurons and ascending sensory information. Behavioural studies showed deficits in motor control and coordination in SCI rats. Cholinergic system plays an important role in SCI, the evaluation of which provides valuable insight on the underlying mechanisms of motor deficit that occur during SCI. The cholinergic transmission was studied by assessing the muscarinic and nicotinic receptors; cholinergic enzymes- ChAT and AChE; second messenger enzyme PLC; transcription factor CREB and second messengers - IP3, cAMP and cGMP. We observed a decrease in the cholinergic transmission in the brain and spinal cord of SCI rats. The disrupted cholinergic system is the indicative of motor deficit and neuronal degeneration in the spinal cord and brain regions. SCI mediated oxidative stress and apoptosis leads to neuronal degeneration in SCI rats. The decreased expression of anti oxidant enzymes – SOD, GPx and neuronal cell survival factors - BDNF, GDNF, IGF-1, Akt and cyclin D2 along with increased expression of apoptotic factors – Bax, caspase-8, TNFa and NF-kB augmented the neuronal degeneration in SCI condition. BMC administration in combination with 5-HT and GABA in SCI rats showed a reversal in the impaired cholinergic neurotransmission and reduced the oxidative stress and apoptosis. It also enhanced the expression of cell survival factors in the spinal cord region. In SCI rats treated with 5-HT and GABA, the transplanted BMC expressed NeuN confirming that 5-HT and GABA induced the differentiation and proliferation of BMC to neurons in the spinal cord. Neurotrophic factors and anti-apoptotic elements in SCI rats treated with 5-HT and GABA along with BMC rendered neuroprotective effects accompanied by improvement in behavioural deficits. This resulted in a significant reversal of altered cholinergic neurotransmission in SCI. The restorative and neuro protective effects of BMC in combination with 5-HT and GABA are of immense therapeutic significance in the clinical management of SCI.

Role of spinal microglia in myositis-induced central sensitisation: An immunohistochemical and behavioural study in rats

There is increasing evidence that spinal glial cells play an important role in chronic pain states. However, so far no data on the role of microglia in muscle pain are available. The aim of the present study was to investigate the involvement of spinal microglial cells in chronic muscle pain. In a rat model of chronic muscle inflammation (injection of complete Freunds adjuvant into the gastrocnemius-soleus muscle) alterations of microglia were visualized with quantitative OX-42 immunohistochemistry in the dorsal horn of the segments L4 and L5 12 days after induction of inflammation. In behavioural experiments the influence of chronic intrathecally applied minocycline - a specific microglia inhibitor - or an antibody against tumour necrosis factor-alpha (TNF-alpha: a cytokine released from microglia) on pain-related behaviour was investigated after 1, 3, 6, and 12 days. The immunhistochemical data show that in the deep laminae of the spinal dorsal horn microglial cells reacted with morphological changes to the muscle inflammation. Following inflammation, the mean boundary length surrounding the OX-42 immunostained area was significantly shorter. This indicates that microglial cells were activated by the myositis and withdrew their processes. Chronic intrathecal administration of minocycline or anti TNF-alpha with an osmotic mini-pump largely normalised the inflammation-induced changes in spontaneous exploratory behaviour and attenuated the hypersensitivity to mechanical stimulation. Both the immunohistochemical and behavioural data show that spinal microglial cells are involved in nociceptive processes in the cause of a chronic muscle inflammation. (C) 2008 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

Postoperative renal function evaluation, through RIFLE criteria, of elderly patients who underwent femur fracture surgery under spinal anesthesia

Introduction. The postoperative acute renal failure (ARF) incidence in different kinds of surgery has rarely been studied. Age, cardiac dysfunction, previous renal dysfunction, intraoperative hypoperfusion, and use of nephrotoxic medications are mentioned as risk factors for ARF at the postoperative period. The postoperative ARF definition was based on the creatinine increase by the RIFLE classification (R = risk, I = injury, F = failure, L = loss, E = end stage), which corresponds to a 1.5 creatinine increase, two to three times, respectively, above the basal value. This study aimed to evaluate the postoperative ARF incidence in elderly patients who underwent femur fracture surgery under subarachnoid anesthesia and stratify it by the RIFLE criteria. Methods. Ninety patients older than 65 years under spinal anesthesia with fixed dosage of 15 mg of 0.5% isobaric bupivacaine associated with morphine 50 g were studied. Immediate postoperative creatinine was considered basal and compared with maximal creatinine evaluated at 24, 48, and 72 postoperative hours. Results. The mean age of the patients was 80.27 years. ARF incidence was 24.44% and stratified this way: R = 21.11% and I = 3.33%. Conclusions. In conclusion, the postoperative ARF incidence after femur fracture surgery in patients over 65 years was 24.44%. By analyzing the stratification based on the RIFLE classification, the incidence was categorized as Risk (R) = 21.11% and Injury (I) = 3.33%.

Contribution of magnetic resonance in acute spinal cord trauma - case report

Acute spinal cord trauma is a common injury that occurs frequently in small animals. In order to acertain a prognosis of the lesion generated in the spinal cord, it is necessary to perform a complete neurological and physical examination, aided by complementary images. Magnetic resonance imaging may be advantageous over other types of images, because it can determine with greater definition the structural damage to the nervous tissue. The objective of this report was to demonstrate the contribution of magnetic resonance imaging in a case of acute spinal cord trauma in a dog.

Does spinal block through tattooed skin cause histological changes in nervous tissue and meninges?: an experimental model in rabbits

Although there is no documented evidence that tattoo pigments can cause neurological complications, the implications of performing neuraxial anesthesia through tattooed skin are unknown. In this study, we aimed to assess whether spinal puncture performed through tattooed skin of rabbits determines changes over the spinal cord and meninges. In addition, we sought to evaluate the presence of ink fragments entrapped in spinal needles. Thirty-six young male adult rabbits, each weighing between 3400 and 3900 g and having a spine length between 38.5 and 39 cm, were divided by lot into 3 groups as follows: GI, spinal puncture through tattooed skin; GII, spinal puncture through tattooed skin and saline injection; and GIII, spinal puncture through skin free of tattoo and saline injection. After intravenous anesthesia with ketamine and xylazine, the subarachnoid space was punctured at S1-S2 under ultrasound guidance with a 22-gauge 2½ Quincke needle. Animals in GII and GIII received 5 μL/cm of spinal length (0.2 mL) of saline intrathecally. In GI, the needle tip was placed into the yellow ligament, and no solution was injected into the intrathecal space; after tattooed skin puncture, 1 mL of saline was injected through the needle over a histological slide to prepare a smear that was dyed by the Giemsa method to enable tissue identification if present. All animals remained in captivity for 21 days under medical observation and were killed by decapitation. The lumbosacral spinal cord portion was removed for histological analysis using hematoxylin-eosin stain. None of the animals had impaired motor function or decreased nociception during the period of clinical observation. None of the animals from the control group (GIII) showed signs of injuries to meninges. In GII, however, 4 animals presented with signs of meningeal injury. The main histological changes observed were focal areas of perivascular lymphoplasmacyte infiltration in the pia mater and arachnoid. There was no signal of injury in neural tissue in any animal of both groups. Tissue coring containing ink pigments was noted in all GI smears from the spinal needles used to puncture the tattooed skin. On the basis of the present results, intrathecal injection of saline through a needle inserted through tattooed skin is capable of producing histological changes over the meninges of rabbits. Ink fragments were entrapped inside the spinal needles, despite the presence of a stylet.

Time-related effects of general functional training in spinal cord-injured rats

OBJECTIVES: This prospective, randomized, experimental study with rats aimed to investigate the influence of general treatment strategies on the motor recovery of Wistar rats with moderate contusive spinal cord injury. METHODS: A total of 51 Wistar rats were randomized into five groups: control, maze, ramp, runway, and sham (laminectomy only). The rats underwent spinal cord injury at the T9-T10 levels using the NYU-Impactor. Each group was trained for 12 minutes twice a week for two weeks before and five weeks after the spinal cord injury, except for the control group. Functional motor recovery was assessed with the Basso, Beattie, and Bresnahan Scale on the first postoperative day and then once a week for five weeks. The animals were euthanized, and the spinal cords were collected for histological analysis. RESULTS: Ramp and maze groups showed an earlier and greater functional improvement effect than the control and runway groups. However, over time, unexpectedly, all of the groups showed similar effects as the control group, with spontaneous recovery. There were no histological differences in the injured area between the trained and control groups. CONCLUSION: Short-term benefits can be associated with a specific training regime; however, the same training was ineffective at maintaining superior long-term recovery. These results might support new considerations before hospital discharge of patients with spinal cord injuries.

Evaluation of the effects of hyperbaric oxygen therapy for spinal cord lesion in correlation with the moment of intervention

Study design: Experimental, controlled, animal study. Objectives: To evaluate the functional effect of hyperbaric oxygen therapy administered shortly, one day after, and no intervention (control) in standardized experimental spinal cord lesions in Wistar rats. Setting: Sao Paulo, Brazil. Methods: In all, 30 Wistar rats with spinal cord lesions were divided into three groups: one group was submitted to hyperbaric oxygen therapy beginning half an hour after the lesion and with a total of 10 one-hour sessions, one session per day, at 2 atm; the second received the same treatment, but beginning on the day after the lesion; and the third received no treatment (control). The Basso, Beattie and Bresnahan scales were used for functional evaluation on the second day after the lesion and then weekly, until being killed 1 month later. Results: There were no significant differences between the groups in the functional analysis on the second day after the lesion. There was no functional difference comparing Groups 1 and 2 (treated shortly after or one day after) in any evaluation moment. On the 7th day, as well as on the 21st and 28th postoperative days, the evaluation showed that Groups 1 and 2 performed significantly better than the control group (receiving no therapy). Conclusion: Hyperbaric chamber therapy is beneficial in the functional recovery of spinal cord lesions in rats, if it is first administered just after spinal cord injury or within 24 h. Spinal Cord (2012) 50, 502-506; doi: 10.1038/sc.2012.16; published online 6 March 2012

Protective and risk factors in amateur equestrians and description of injury patterns: A retrospective data analysis and a case - control survey

Background In Switzerland there are about 150,000 equestrians. Horse related injuries, including head and spinal injuries, are frequently treated at our level I trauma centre. Objectives To analyse injury patterns, protective factors, and risk factors related to horse riding, and to define groups of safer riders and those at greater risk Methods We present a retrospective and a case-control survey at conducted a tertiary trauma centre in Bern, Switzerland. Injured equestrians from July 2000 - June 2006 were retrospectively classified by injury pattern and neurological symptoms. Injured equestrians from July-December 2008 were prospectively collected using a questionnaire with 17 variables. The same questionnaire was applied in non-injured controls. Multiple logistic regression was performed, and combined risk factors were calculated using inference trees. Results Retrospective survey A total of 528 injuries occured in 365 patients. The injury pattern revealed as follows: extremities (32%: upper 17%, lower 15%), head (24%), spine (14%), thorax (9%), face (9%), pelvis (7%) and abdomen (2%). Two injuries were fatal. One case resulted in quadriplegia, one in paraplegia. Case-control survey 61 patients and 102 controls (patients: 72% female, 28% male; controls: 63% female, 37% male) were included. Falls were most frequent (65%), followed by horse kicks (19%) and horse bites (2%). Variables statistically significant for the controls were: Older age (p = 0.015), male gender (p = 0.04) and holding a diploma in horse riding (p = 0.004). Inference trees revealed typical groups less and more likely to suffer injury. Conclusions Experience with riding and having passed a diploma in horse riding seem to be protective factors. Educational levels and injury risk should be graded within an educational level-injury risk index.

Spinal and pelvic injuries in airborne sports: a retrospective analysis from a major Swiss trauma centre

Adrenalin-seeking airborne sports like BASE-jumping, paragliding, parachuting, delta-gliding, speedflying, and skysurfing are now firmly with us as outdoor lifestyle activities and are associated with a high frequency of severe injuries, especially to the spine.

Vascular Diseases of the Spinal Cord: A Review

OPINION STATEMENT: • In acute spinal cord ischemia syndrome (ASCIS), treatment recommendations are derived from data of cerebral ischemic stroke, atherosclerotic vascular disease and acute spinal cord injury. Besides acute management, secondary prevention is of major importance. Pathologies affecting the aorta as well as underlying cerebrovascular conditions should be treated whenever possible.• ASCIS may occur after aortic surgery, less often after thoracic endovascular aortic repair (TEVAR). Protocols are proposed.• Acute spinal cord hemorrhage can be treated surgically and/or pharmacologically.• Symptomatic treatment in patients with a spinal cord lesion is of major importance. Depending on level and extension of the lesion, there is a risk for systemic and neurological complications, which may be life-threatening.• Each spinal vascular malformation is a unique lesion that needs an individualized treatment algorithm. In case of a symptomatic vascular malformation, endovascular intervention is the primary treatment option.• Spinal dural Arteriovenous fistula (AVF) may be treated endovascularly or surgically. If preoperative localization of the fistula is possible, surgery is feasible with a low complication rate. In comparison, endovascular approaches are less invasive.• Spinal AVM are rather treated endovascularly than surgically or in a stepwise multidisciplinary approach.• Symptomatic and exophytic spinal cavernous angiomas should be treated surgically. Deep spinal cavernous angiomas that are asymptomatic or only show mild symptoms can be observed.

Epidemiology and predictors of cervical spine injury in adult major trauma patients: a multicenter cohort study

Patients with cervical spine injuries are a high-risk group, with the highest reported early mortality rate in spinal trauma.

Gait analysis in normal and spinal contused mice using the TreadScan system

Advances in spinal cord injury (SCI) research are dependent on quality animal models, which in turn rely on sensitive outcome measures able to detect functional differences in animals following injury. To date, most measurements of dysfunction following SCI rely either on the subjective rating of observers or the slow throughput of manual gait assessment. The present study compares the gait of normal and contusion-injured mice using the TreadScan system. TreadScan utilizes a transparent treadmill belt and a high-speed camera to capture the footprints of animals and automatically analyze gait characteristics. Adult female C57Bl/6 mice were introduced to the treadmill prior to receiving either a standardized mild, moderate, or sham contusion spinal cord injury. TreadScan gait analyses were performed weekly for 10 weeks and compared with scores on the Basso Mouse Scale (BMS). Results indicate that this software successfully differentiates sham animals from injured animals on a number of gait characteristics, including hindlimb swing time, stride length, toe spread, and track width. Differences were found between mild and moderate contusion injuries, indicating a high degree of sensitivity within the system. Rear track width, a measure of the animal's hindlimb base of support, correlated strongly both with spared white matter percentage and with terminal BMS. TreadScan allows for an objective and rapid behavioral assessment of locomotor function following mild-moderate contusive SCI, where the majority of mice still exhibit hindlimb weight support and plantar paw placement during stepping.

Gene expression profiling in anti-CD11d mAb-treated spinal cord-injured rats

Acute administration of a mononclonal antibody (mAb) raised against the CD11d subunit of the leukocyte CD11d/CD18 integrin after spinal cord injury (SCI) in the rat greatly improves neurological outcomes. We have profiled gene expression in anti-CD11d and isotyped-matched control mAb-treated rats after SCI. Microarray analysis demonstrated reduced expression of pro-inflammatory cytokines and increased expression of inflammatory mediators that promote wound healing and the expression of scar proteins predicted to improve nerve growth. These changes in gene expression may reflect changes in the types of macrophages that populate the lesions in anti-CD11d mAb-treated rats.

Genetic networks controlling retinal injury.

PURPOSE: The present study defines genomic loci underlying coordinate changes in gene expression following retinal injury. METHODS: A group of acute phase genes expressed in diverse nervous system tissues was defined by combining microarray results from injury studies from rat retina, brain, and spinal cord. Genomic loci regulating the brain expression of acute phase genes were identified using a panel of BXD recombinant inbred (RI) mouse strains. Candidate upstream regulators within a locus were defined using single nucleotide polymorphism databases and promoter motif databases. RESULTS: The acute phase response of rat retina, brain, and spinal cord was dominated by transcription factors. Three genomic loci control transcript expression of acute phase genes in brains of BXD RI mouse strains. One locus was identified on chromosome 12 and was highly correlated with the expression of classic acute phase genes. Within the locus we identified the inhibitor of DNA binding 2 (Id2) as a candidate upstream regulator. Id2 was upregulated as an acute phase transcript in injury models of rat retina, brain, and spinal cord. CONCLUSIONS: We defined a group of transcriptional changes associated with the retinal acute injury response. Using genetic linkage analysis of natural transcript variation, we identified regulatory loci and candidate regulators that control transcript levels of acute phase genes.

Astrocytes from the contused spinal cord inhibit oligodendrocyte differentiation of adult oligodendrocyte precursor cells by increasing the expression of bone morphogenetic proteins.

Promotion of remyelination is an important therapeutic strategy to facilitate functional recovery after traumatic spinal cord injury (SCI). Transplantation of neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) has been used to enhance remyelination after SCI. However, the microenvironment in the injured spinal cord is inhibitory for oligodendrocyte (OL) differentiation of NSCs or OPCs. Identifying the signaling pathways that inhibit OL differentiation in the injured spinal cord could lead to new therapeutic strategies to enhance remyelination and functional recovery after SCI. In the present study, we show that reactive astrocytes from the injured rat spinal cord or their conditioned media inhibit OL differentiation of adult OPCs with concurrent promotion of astrocyte differentiation. The expression of bone morphogenetic proteins (BMP) is dramatically increased in the reactive astrocytes and their conditioned media. Importantly, blocking BMP activity by BMP receptor antagonist, noggin, reverse the effects of active astrocytes on OPC differentiation by increasing the differentiation of OL from OPCs while decreasing the generation of astrocytes. These data indicate that the upregulated bone morphogenetic proteins in the reactive astrocytes are major factors to inhibit OL differentiation of OPCs and to promote its astrocyte differentiation. These data suggest that manipulation of BMP signaling in the endogenous or grafted NSCs or OPCs may be a useful therapeutic strategy to increase their OL differentiation and remyelination and enhance functional recovery after SCI.