Spinal cord injury (SCI) manifests signs of spasticity, plantar flexor (PF) hyperreflexia and ankle clonus, and deficits in motor function. In individuals with motor-incomplete SCI (MISCI), ankle clonus may limit independent walking function. Ankle clonus is attributed to enhanced soleus stretch reflex (SSR) excitability due to decreased supraspinal input and maladaptive reorganization of spinal reflex circuitry. We explored these questions: 1. What are the biomechanical, clinical, and neurophysiologic correlates of ankle clonus? 2. Does locomotor training improve ankle clonus and walking function? 3. Will operant conditioning-based interventions that increase tibialis anterior activation or decrease soleus reflex excitability improve ankle motor control and walking function? In Chapter 2 we compared Ankle Clonus Drop Test (Drop Test) measures with clinical and neurophysiologic measures. Drop Test measures were highly reliable and exhibited moderate to strong correlations with clinical and neurophysiologic measures. Analysis of EMG activity during clonus revealed a predominant pattern of antagonist coactivation. In Chapter 3 we investigated the effects of locomotor training on PF and quadriceps spasticity, and walking function. We assessed responsiveness of the PF reflex threshold angle, a Drop Test measure of PF spasticity. PF and quadriceps spasticity decreased after locomotor training and were moderately correlated with increased walking speed. The PF reflex threshold angle measure discriminated between individuals with and without clonus. In Chapter 4 we compared the effects of two operant-conditioning based interventions to, (1) increase TA EMG activation (TA↑) and (2) decrease SOL H-reflex amplitude during active dorsiflexion (SOL↓), on reflex modulation, ankle motor control, and walking function. Each intervention improved walking function; however, modulated the variables in unique ways. TA↑ improved deficits of strength and range of motion, and SOL↓ improved modulation of SSR and SOL/TA coactivation. In Chapter 5 we discussed implications of our conclusions: (1) Drop Test ankle clonus measures are valid, reliable, and responsive; (2) antagonist coactivation was predominant during ankle clonus; (3) in individuals with chronic MISCI, locomotor training decreased PF and quadriceps spasticity and improved walking function; and (4) an operant conditioning-based intervention to either increase TA strength or decrease SOL reflex excitability improved spinal reflex modulation and walking function.

Macrophages (monocytes/microglia) could play a critical role in central nervous system repair. We have previously found a synchronism between the regression of spontaneous axonal regeneration and the deactivation of macrophages 34 wk after a compression-injury of rat spinal cord. To explore whether reactivation of endogenous macrophages might be beneficial for spinal cord repair, we have studied the effects of granulocyte-macrophage colony stimulating factor (GM-CSF) in the same paraplegia model and in cell cultures. There is significant, though transient, improvement of locomotor recovery after a single delayed intraperitoneal injection of 2g GM-CSF. This improvement is associated with an increased expression of 5HT at the level of the CPG (T13-L2). At longer survival delays, axonal regeneration is significantly enhanced in GM-CSF-treated rats. We then studied the effects of GM-CSF on brain-derived neurotrophic factor (BDNF)secretion by macrophages/microglia, inflammatory reaction and phagocytosis by macrophages/microglia. In vivo, at short post-treatment delays, we found that GM-CSF increases significantly the expression of Cr3 and BDNF by macrophages at the lesion site. In vitro, BV2 microglial cells expressed higher levels of BDNF in the presence of GM-CSF and neurons cocultured with microglial cells activated by GM-CSF generated more neurites, an effect blocked by a BDNF antibody. In vivo, we showed that GM-CSF treatment (either immediate or delayed) does not increase IL-6 expression by macrophages/microglia or astrocytes. We showed that a delayed GM-CSF treatment down regulates IL-1 expression by astrocytes. In vivo, we showed that a delayed GM-CSF treatment can decrease MAG expression at the lesion site. These experiments suggest that GM-CSF could be an interesting treatment option for spinal cord injury and that its beneficial effects might be mediated by BDNF.

<p>Spinal cord injury is a devastating condition, and its consequences impact on many facets of an individual&rsquo / s life. Activities of daily living such as personal care and housework might be difficult to perform post injury. The majority of spinal cord injury patients receive hospital-based rehabilitation to address these consequences. The normal length of hospital stay among spinal cord injury patients ranges from three to twelve months, and an increased length of stay are caused by development of secondary complications such as pressure sores, urinary tract infection and respiratory infection. The purpose of this study was to determine factors affecting length of hospital stay for individuals with spinal cord injuries at Kanombe Military Hospital in Rwanda. To achieve this, a retrospective study, utilising a quantitative approach was used. The records of individuals with spinal cord injuries discharged from the hospital between 1st January1996 and 31st December 2007 were reviewed to collect data. A data gathering instrument was developed by the researcher and there after used to capture the relevant information from the patients&rsquo / folders. Information collected included demographic data, information relating to the injury, occurrence of medical complications and length of hospital stay. One hundred and twenty four medical folders of patients discharged from 1st January 1996 to 31st December 2007 at Kanombe Military Hospital were reviewed for data extraction. The Statistical Package for Social Sciences (SPSS) version 16.0 for windows was used to analyse the data. Both descriptive and inferential statistics were determined in SPSS. Associations were made between demographic factors and occurrence of secondary medical complications with length of hospital stay. These were computed by means of chi-square tests. One level of significance, alpha set at 5% was used throughout. The linear regression analysis was used to determine factors affecting the length of stay.</p>

Background: Spinal cord injury (SCI) is heterogeneous in nature and can be complicated by inflammation and scarring in the subarachnoid space (arachnoiditis). The constellation of traumatic injury and arachnoiditis can lead to extensive intraparenchymal cysts or post-traumatic syringomyelia (PTS), due to alterations in fluid flow and pressure dynamics in the subarachnoid space. Hypothesis: Intrathecal injection of a bioengineered hydrogel containing hyaluronan (HA) will improve functional recovery following severe spinal cord injury associated with arachnoiditis. Methods: Acute to subacute pathophysiological events were characterized in non-injured sham rats, rats receiving a clip compression/contusion injury (SCI), rats receiving an intrathecal kaolin injection (Arachnoiditis) and in rats receiving SCI plus kaolin injection (PTS). Next, a HA containing hydrogel (HAMC) or artificial cerbralspinal fluid (aCSF) control was injected into the subarachnoid space 24 hours following PTS injury. To assess treatment efficacy, subacute pathophysiology was assessed as was long-term neurobehavioural and neuroanatomical recovery. Finally, in vitro studies examined the effect of HA on TLR4 activation using lipopolysaccharide in primary rat microglial cultures. Results: PTS animals exhibited a greater parenchymal injury response as compared to the sum of SCI alone or arachnoiditis alone. Injection of HAMC reduced the extent of scarring and inflammation in the subarachnoid space and improved neurobehavioural and neuroanatomical recovery relative to aCSF controls. These improvements were associated with reduced chondroitin sulfate proteoglycan and IL-1α expression and a trend towards and axonal preservation. In vitro studies demonstrated that HA is capable of reducing TLR4 mediated inflammation in microglia. Conclusions: Acute arachnoiditis potentiates the intensity of intraparenchymal inflammatory and scarring events following SCI. When HAMC was injected intrathecally following PTS injury, it mitigated some of the pernicious effects of arachnoiditis. Part of the therapeutic action of HAMC can be attributed to the ability of HA to reduce TLR4 mediated inflammation in microglia, possibly through an extracellular mechanism.

Orthostatic hypotension (OH) is a prevalent condition among individuals with spinal cord injury (SCI). After an injury, OH often reduces the benefit of neurorehabilitation and also prolongs periods of inactivity that lead to secondary complications. This study investigated whether the cardiovascular response to head-up tilting can be improved using functional electrical stimulation (FES) and rhythmic passive movements of the lower extremities. Participants with high thoracic and cervical SCI were recruited. While the participants were tilted head-up to 70 degrees, four conditions were applied in a random sequence: 1) no intervention, 2) rhythmic passive leg movements, 3) isometric FES, and 4) a combination of FES and passive leg movements. The measured cardiovascular parameters indicated that a combination of FES and passive leg movements induced the most desirable response to head-up tilting. The proposed intervention will enable more individuals with SCI to participate in beneficial neurorehabilitation that uses a novel tilt table.

In two separate studies, we used diffusion tensor imaging (DTI)to examine white matter changes secondary to traumatic brain injury (TBI) and spinal cord injury (SCI). The first study examined the utility of DTI for a single case diagnosis of mild TBI (mTBI) and demonstrated that the anterior limb of the internal capsule and the genu of the corpus callosum were sensitive and specific to mTBI. The second study examined the sub-acute effects of SCI on white matter tissue in the brain and demonstrated that SCI patients have a significantly greater degree of FA asymmetry than control subjects in the superior and posterior corona radiata. The first study has provided preliminary proof of principal evidence that DTI can be used to diagnose mTBI in individual cases. The second study suggests that the degree of asymmetry may be a useful biomarker for detecting subtle white matter changes.

Orthostatic hypotension (OH) is a prevalent condition among individuals with spinal cord injury (SCI). After an injury, OH often reduces the benefit of neurorehabilitation and also prolongs periods of inactivity that lead to secondary complications. This study investigated whether the cardiovascular response to head-up tilting can be improved using functional electrical stimulation (FES) and rhythmic passive movements of the lower extremities. Participants with high thoracic and cervical SCI were recruited. While the participants were tilted head-up to 70 degrees, four conditions were applied in a random sequence: 1) no intervention, 2) rhythmic passive leg movements, 3) isometric FES, and 4) a combination of FES and passive leg movements. The measured cardiovascular parameters indicated that a combination of FES and passive leg movements induced the most desirable response to head-up tilting. The proposed intervention will enable more individuals with SCI to participate in beneficial neurorehabilitation that uses a novel tilt table.

In two separate studies, we used diffusion tensor imaging (DTI)to examine white matter changes secondary to traumatic brain injury (TBI) and spinal cord injury (SCI). The first study examined the utility of DTI for a single case diagnosis of mild TBI (mTBI) and demonstrated that the anterior limb of the internal capsule and the genu of the corpus callosum were sensitive and specific to mTBI. The second study examined the sub-acute effects of SCI on white matter tissue in the brain and demonstrated that SCI patients have a significantly greater degree of FA asymmetry than control subjects in the superior and posterior corona radiata. The first study has provided preliminary proof of principal evidence that DTI can be used to diagnose mTBI in individual cases. The second study suggests that the degree of asymmetry may be a useful biomarker for detecting subtle white matter changes.

The primary purpose of this study was to determine the effect of ingesting an 8% carbohydrate (CHO) beverage during a moderate intensity exercise trial on performance outcomes, fuel utilization and blood glucose levels of wheelchair athletes (spinal cord injury (SC I) or cerebral palsy (CP)). The secondary purpose was to analyze the dietary intake of the eight participants and to determine if they were meeting current sport nutrition guidelines for macronutrients and fluids recommended in the joint position statement developed by the American Dietetic Association (ADA), the American College of Sports Medicine (ACSM) and Dietitians of Canada (DC).<p> Under random, double blind conditions eight athletes (6 males, 2 females); mean age 36 ± 8.5 y with a SCI (n = 7) or CP (n = 1) completed two exercise trials on an adapted stationary hand cycle; each trial was 60 minutes in duration at 65 % VO2peak followed immediately by a 30-minute performance trial. During the first 60-minutes the participants were given four 200 ml dosages (15, 30, 45, 60-min) of an 8% CHO beverage or a taste-matched placebo beverage. Blood lactate and glucose levels were sampled during the 60-minute exercise trial (pre, 20, 40, 60-min) and immediately after the 30-minute performance trial (post, 2, 5, 10-min). Heart rate was monitored continuously during the exercise and performance trial. Expired gas samples were also taken for 5-min periods during the exercise trial and then continuously during the performance trial. These values were used to calculate respiratory exchange ratio (RER) and carbohydrate oxidation. Dietary intake was assessed with a three day food record.<p> No significant differences were apparent between beverage trials for total distance (km), average speed (kmhr-1) or maximum speed achieved (kmhr-1). Significant differences were evident for blood glucose values, RER and CHO oxidation between the two beverage trials (p< .05). At the end of the 30-minute performance trial blood glucose values were significantly higher in the CHO trial (4.8 ± 1.3 mmol.l-1 vs. 4.0 ± 0.5 mmol.l-1 for placebo trial; p< .05). The CHO beverage resulted in higher CHO oxidation during the last 5 minutes of the performance trial, 2.1 ± 1.0 gmin-1 vs. the placebo beverage 1.9 ± 1.0 gmin-1 (p< .05). The CHO beverage trial resulted in significantly higher RER values during the final 5 minutes of the exercise trial and during the final 10 minutes of the performance trial. At the 20-25 minute mark RER values were significantly higher with the CHO beverage trial (1.04 ± 0.10) vs. the placebo trial (1.01 ± 0.11) (p< .05). During the final 5 minutes of the performance trial RER values were also significantly higher with the CHO beverage trial (1.06 ± 0.11) vs. the placebo trial (1.01 ± 0.10) (p< .05). The results indicated the participants were not meeting the current dietary guidelines for able-bodied athletes and active adults. Only 25% of the participants met the daily caloric requirements for active adults. Carbohydrate recommendations of 6 to 10 gkg-1 body weightd -1 were not met by any of the wheelchair athletes Seven participants were within the acceptable macronutrient range (AMDR) for CHO. For protein intake, 63% of the participants were meeting the protein recommendations active adults and all of them were within the AMDR. Average caloric intake from fat exceeded current recommendations of 20 to 25%; two participants were above the AMDR. The results demonstrate that the 8% CHO beverage consumed during exercise resulted in higher CHO oxidation rates and elevated blood glucose values, but it did not result in a performance gain.

Spinal cord injury (SCI) is a devastating condition characterized by the loss of neuronal pathways responsible for coordinating motor and sensory information between the brain and the rest of the body. The mammalian spinal cord is limited in its ability to repair itself, so treatments devised to replace damaged tissue and promote regeneration are essential towards developing a cure. This work describes the development of a guidance channel strategy for spinal cord transection. Chitosan guidance channels were designed as a delivery vehicle for neural stem/progenitor cell (NSPC) transplants and drug-eluting poly(lactic-co-glycolic acid) (PLGA) microspheres. PLGA microspheres were embedded into chitosan channels by a spin-coating method. These microsphere-loaded channels demonstrated the ability for controlled short-term bioactive release of the small molecule drug dibutyryl cyclic-AMP (dbcAMP) and long-term bioactive release of the protein alkaline phosphatase. NSPCs were shown to be responsive to dbcAMP delivery, which results in greatly enhanced differentiation into neurons. The effect of directed neuronal differentiation was investigated after spinal cord transection in rat, resulting in a dramatic increase in NSPC transplant survival. Guidance channels containing NSPCs treated with dbcAMP resulted in robust tissue bridge formation after SCI, demonstrating extensive axonal regeneration and promoting functional recovery.