Background Knowledge of the body's response to and recovery from exercise is rapidly increasing. State-of-the-art equipment and facilities allow recreationally active adults to seek innovations to enhance performance and shorten recovery time. Myofascial rolling (MR) is a relatively new practice, providing acute benefits for muscle pain and range of motion (ROM). However, there is no consensus on optimal MR duration. Purpose The purpose of this systematic review is to determine the optimal MR duration using a foam roller or a roller massager for muscle pain, ROM, and athletic performance via qualitative review. Study Design Systematic Review of the Literature. Methods A systematic search was conducted using PubMed, EMBASE, EBSCOHost and PEDro (July 2018). Twenty-two studies met the inclusion criteria and were appraised using the PEDro scale. Studies were grouped by outcome measure, with a total number of subjects of n = 328 for pain/soreness, n = 398 for ROM, and n = 241 for performance. Heterogeneity of data prohibited a formal meta-analysis: studies were manually reviewed and classified as providing evidence for benefit of MR (i.e., significant positive effect) or not (i.e., null or negative effect) for each of the studied outcomes. Results The most evidence-based benefit of MR is the alleviation of muscle soreness; seven of eight studies assessing pain/soreness resulted in a short-term reduction, and a minimum dose of 90 seconds per muscle appeared beneficial. While ten of 17 studies involving ROM showed acute improvements, the results were inconsistent and highly variable. No significant effects on performance were detected. Conclusion Available data indicate that MR for 90 seconds per muscle group may be the minimal duration to achieve a short-term reduction in pain/soreness, with no upper limit found. Results do not support increases in chronic ROM or performance, and data are insufficient to provide a conclusive recommendation for impacting acute ROM. The heterogeneity of the literature highlights the need for additional research to determine optimal dose of MR. Level of evidence 2a- (Systematic Review with heterogeneity).

Introduction Recent studies demonstrate that cardiovascular diseases and associated complications are the leading cause of morbidity and mortality in individuals with spinal cord injury (SCI). Abnormal arterial stiffness, defined by a carotid–to-femoral pulse wave velocity (cfPWV) ≥10 m/s, is a recognised risk factor for heart disease in individuals with SCI. There is a paucity of studies assessing the efficacy of conventional training modalities on arterial stiffness and other cardiovascular outcomes in this population. Therefore, this study aims to compare the efficacy of arm cycle ergometry training (ACET) and body weight-supported treadmill training (BWSTT) on reducing arterial stiffness in individuals with chronic motor complete, high-level (above the sixth thoracic segment) SCI. Methods and analysis This is a multicentre, randomised, controlled, clinical trial. Eligible participants will be randomly assigned (1:1) into either ACET or BWSTT groups. Sixty participants with chronic (>1 year) SCI will be recruited from three sites in Canada (Vancouver, Toronto and Hamilton). Participants in each group will exercise three times per week up to 30 min and 60 min for ACET and BWSTT, respectively, over the period of 6 months. The primary outcome measure will be change in arterial stiffness (cfPWV) from baseline. Secondary outcome measures will include comprehensive assessments of: (1) cardiovascular parameters, (2) autonomic function, (3) body composition, (4) blood haematological and metabolic profiles, (5) cardiorespiratory fitness and (6) quality of life (QOL) and physical activity outcomes. Outcome measures will be assessed at baseline, 3 months, 6 months and 12 months (only QOL and physical activity outcomes). Statistical analyses will apply linear-mixed modelling to determine the training (time), group (ACET vs BWSTT) and interaction (time × group) effects on all outcomes. Ethics and dissemination Ethical approval was obtained from all three participating sites. Primary and secondary outcome data will be submitted for publication in peer-reviewed journals and widely disseminated. Trial registration number NCT01718977 ; Pre-results. Trial status Recruitment for this study began on January 2013 and the first participant was randomized on April 2013. Recruitment stopped on October 2018.

Glutamine synthetase, encoded by the gene GLUL , is an enzyme that converts glutamate and ammonia to glutamine. It is expressed by endothelial cells, but surprisingly shows negligible glutamine-synthesizing activity in these cells at physiological glutamine levels. Here we show in mice that genetic deletion of Glul in endothelial cells impairs vessel sprouting during vascular development, whereas pharmacological blockade of glutamine synthetase suppresses angiogenesis in ocular and inflammatory skin disease while only minimally affecting healthy adult quiescent endothelial cells. This relies on the inhibition of endothelial cell migration but not proliferation. Mechanistically we show that in human umbilical vein endothelial cells GLUL knockdown reduces membrane localization and activation of the GTPase RHOJ while activating other Rho GTPases and Rho kinase, thereby inducing actin stress fibres and impeding endothelial cell motility. Inhibition of Rho kinase rescues the defect in endothelial cell migration that is induced by GLUL knockdown. Notably, glutamine synthetase palmitoylates itself and interacts with RHOJ to sustain RHOJ palmitoylation, membrane localization and activation. These findings reveal that, in addition to the known formation of glutamine, the enzyme glutamine synthetase shows unknown activity in endothelial cell migration during pathological angiogenesis through RHOJ palmitoylation.

Recovery from acute spinal cord injury (SCI) is characterized by extensive heterogeneity, resulting in uncertain prognosis. Reliable prediction of recovery in the acute phase benefits patients and their families directly, as well as improves the likelihood of detecting efficacy in clinical trials. This issue of heterogeneity is not unique to SCI. In fields such as traumatic brain injury, Parkinson's disease, and amyotrophic lateral sclerosis, one approach to understand variability in recovery has been to make clinical trial data widely available to the greater research community. We contend that the SCI community should adopt a similar approach in providing open access clinical trial data.

Spontaneous remyelination occurs after spinal cord injury (SCI), but the extent of myelin repair and identity of the cells responsible remain incompletely understood and contentious. We assessed the cellular origin of new myelin by fate mapping platelet-derived growth factor receptor α (PDGFRα), Olig2+, and P0+ cells following contusion SCI in mice. Oligodendrocyte precursor cells (OPCs; PDGFRα+) produced oligodendrocytes responsible for de novo ensheathment of ∼30% of myelinated spinal axons at injury epicenter 3 months after SCI, demonstrating that these resident cells are a major contributor to oligodendrocyte regeneration. OPCs also produced the majority of myelinating Schwann cells in the injured spinal cord; invasion of peripheral myelinating (P0+) Schwann cells made only a limited contribution. These findings reveal that PDGFRα+ cells perform diverse roles in CNS repair, as multipotential progenitors that generate both classes of myelinating cells. This endogenous repair might be exploited as a therapeutic target for CNS trauma and disease. SIGNIFICANCE STATEMENT Spinal cord injury (SCI) leads to profound functional deficits, though substantial numbers of axons often survive. One possible explanation for these deficits is loss of myelin, creating conduction block at the site of injury. SCI leads to oligodendrocyte death and demyelination, and clinical trials have tested glial transplants to promote myelin repair. However, the degree and duration of myelin loss, and the extent and mechanisms of endogenous repair, have been contentious issues. Here, we use genetic fate mapping to demonstrate that spontaneous myelin repair by endogenous oligodendrocyte precursors is much more robust than previously recognized. These findings are relevant to many types of CNS pathology, raising the possibility that CNS precursors could be manipulated to repair myelin in lieu of glial transplantation.

We thank Kunte and colleagues for their remarks on our paper and for their comment on sulphonylureas as a potential treatment option for spinal cord injury (SCI). We did not include the scientific literature on inhibition of the sulfonylurea receptor 1–transient receptor potential melastatin 4 (SUR1–TRPM4) channel as a means to reduce secondary oedema and haemorrhage after CNS trauma because this has been studied predominantly in stroke and traumatic brain injury. In our Review1Ramer LM Ramer MS Bradbury EJ Restoring function after spinal cord injury: towards clinical translation of experimental strategies.Lancet Neurol. 2014; 13: 1241-1256Summary Full Text Full Text PDF PubMed Scopus (187) Google Scholar article, we prioritised experimental treatments that, in our opinion, were the most promising, the most advanced, or both, and were well replicated in animal models of SCI. Although extensive preclinical evidence exists for the beneficial role of sulfonylureas in rodent models of stroke, and several retrospective analyses show beneficial effects in patients with stroke, evidence for benefit after SCI is less clear cut.Research on SUR1–TRPM4 inhibition and potential benefits of glibenclamide off-label treatment for SCI has come mainly from the laboratory of J Marc Simard, one of the coauthors of the correspondence. The Simard laboratory first identified SUR1–TRPM4 channels as mediators of progressive haemorrhage after SCI and showed attenuation of secondary intraspinal haemorrhage and functional improvements in rats with severe cervical SCI treated with glibenclamide,2Simard JM Tsymbalyuk O Ivanov A et al.Endothelial sulfonylurea receptor 1–regulated NCCa-ATP channels mediate progressive hemorrhagic necrosis following spinal cord injury.J Clin Invest. 2007; 117: 2105-2113Crossref PubMed Scopus (150) Google Scholar with results of several subsequent studies confirming these effects. One attempt to replicate the original study3Popovich PG Lemeshow S Gensel JC Tovar CA Independent evaluation of the effects of glibenclamide on reducing progressive hemorrhagic necrosis after cervical spinal cord injury.Exp Neurol. 2012; 233: 615-622Crossref PubMed Scopus (45) Google Scholar was partly successful in that glibenclamide treatment reduced post-traumatic haemorrhage and improved functional recovery, but only in animals with a specific type of lateralised hemicontusion injury. In medial hemicontusion injuries, in which extent of primary haemorrhage was more severe, glibenclamide was ineffective. Differences in primary trauma seem to affect the efficacy of glibenclamide, with the magnitude of the benefit depending on extent of primary haemorrhage. Therefore, more experimental work is needed to ascertain whether glibenclamide, and other methods of inhibition of SUR1–TRPM4 channels, will be applicable to most traumatic SCIs, or whether this intervention should be targeted for specific types of injury (eg, mild or lateralised injuries). This information will be important for translation of this intervention to a treatment for SCI and for future patient selection.Although we found the data rather premature for inclusion in our article, we appreciate the potential for SUR1–TRPM4 inhibition for alleviation of aspects of secondary damage after CNS trauma. Since glibenclamide has been available and used for decades for treatment of adult-onset diabetes and is in clinical trials for stroke and traumatic brain injury (ClinicalTrials.gov identifiers: NCT01794182 and NCT01454154), it could readily be repurposed for SCI. Therefore, we agree with Kunte and colleagues that SUR1–TRPM4 inhibition certainly deserves further investigation as a treatment for SCI.Finally, another potential link between sulfonylureas and beneficial outcome after SCI is worth noting. Work from Seiji Okada's group has shown that high glucose at the time of SCI leads to increased tissue damage and poor functional outcome in mice with contusion SCIs and that hyperglycaemia on admission was a clinically significant risk predictor of poor functional outcome in patients with SCI.4Kobayakawa K Kumamaru H Saiwai H et al.Acute hyperglycemia impairs functional improvement after spinal cord injury in mice and humans.Sci Transl Med. 2014; 6: 256ra137Crossref PubMed Scopus (39) Google Scholar Since glibenclamide and other sulfonylurea derivatives used in diabetes management increase insulin release from pancreatic β cells, leading to reduced blood glucose levels, this could be a contributing factor to its potential benefits after CNS trauma. Further experimentation is warranted to identify the mechanism (or mechanisms) and the applicability of sulfonylureas for SCI. The specialty awaits work on SUR1–TRPM4 inhibition with interest, because potent neuroprotective agents are urgently needed to improve the outcome of SCI.EJB holds a patent (0205022.7) “Materials and methods for the treatment of CNS damage”. All other authors declare no competing interests. We thank Kunte and colleagues for their remarks on our paper and for their comment on sulphonylureas as a potential treatment option for spinal cord injury (SCI). We did not include the scientific literature on inhibition of the sulfonylurea receptor 1–transient receptor potential melastatin 4 (SUR1–TRPM4) channel as a means to reduce secondary oedema and haemorrhage after CNS trauma because this has been studied predominantly in stroke and traumatic brain injury. In our Review1Ramer LM Ramer MS Bradbury EJ Restoring function after spinal cord injury: towards clinical translation of experimental strategies.Lancet Neurol. 2014; 13: 1241-1256Summary Full Text Full Text PDF PubMed Scopus (187) Google Scholar article, we prioritised experimental treatments that, in our opinion, were the most promising, the most advanced, or both, and were well replicated in animal models of SCI. Although extensive preclinical evidence exists for the beneficial role of sulfonylureas in rodent models of stroke, and several retrospective analyses show beneficial effects in patients with stroke, evidence for benefit after SCI is less clear cut. Research on SUR1–TRPM4 inhibition and potential benefits of glibenclamide off-label treatment for SCI has come mainly from the laboratory of J Marc Simard, one of the coauthors of the correspondence. The Simard laboratory first identified SUR1–TRPM4 channels as mediators of progressive haemorrhage after SCI and showed attenuation of secondary intraspinal haemorrhage and functional improvements in rats with severe cervical SCI treated with glibenclamide,2Simard JM Tsymbalyuk O Ivanov A et al.Endothelial sulfonylurea receptor 1–regulated NCCa-ATP channels mediate progressive hemorrhagic necrosis following spinal cord injury.J Clin Invest. 2007; 117: 2105-2113Crossref PubMed Scopus (150) Google Scholar with results of several subsequent studies confirming these effects. One attempt to replicate the original study3Popovich PG Lemeshow S Gensel JC Tovar CA Independent evaluation of the effects of glibenclamide on reducing progressive hemorrhagic necrosis after cervical spinal cord injury.Exp Neurol. 2012; 233: 615-622Crossref PubMed Scopus (45) Google Scholar was partly successful in that glibenclamide treatment reduced post-traumatic haemorrhage and improved functional recovery, but only in animals with a specific type of lateralised hemicontusion injury. In medial hemicontusion injuries, in which extent of primary haemorrhage was more severe, glibenclamide was ineffective. Differences in primary trauma seem to affect the efficacy of glibenclamide, with the magnitude of the benefit depending on extent of primary haemorrhage. Therefore, more experimental work is needed to ascertain whether glibenclamide, and other methods of inhibition of SUR1–TRPM4 channels, will be applicable to most traumatic SCIs, or whether this intervention should be targeted for specific types of injury (eg, mild or lateralised injuries). This information will be important for translation of this intervention to a treatment for SCI and for future patient selection. Although we found the data rather premature for inclusion in our article, we appreciate the potential for SUR1–TRPM4 inhibition for alleviation of aspects of secondary damage after CNS trauma. Since glibenclamide has been available and used for decades for treatment of adult-onset diabetes and is in clinical trials for stroke and traumatic brain injury (ClinicalTrials.gov identifiers: NCT01794182 and NCT01454154), it could readily be repurposed for SCI. Therefore, we agree with Kunte and colleagues that SUR1–TRPM4 inhibition certainly deserves further investigation as a treatment for SCI. Finally, another potential link between sulfonylureas and beneficial outcome after SCI is worth noting. Work from Seiji Okada's group has shown that high glucose at the time of SCI leads to increased tissue damage and poor functional outcome in mice with contusion SCIs and that hyperglycaemia on admission was a clinically significant risk predictor of poor functional outcome in patients with SCI.4Kobayakawa K Kumamaru H Saiwai H et al.Acute hyperglycemia impairs functional improvement after spinal cord injury in mice and humans.Sci Transl Med. 2014; 6: 256ra137Crossref PubMed Scopus (39) Google Scholar Since glibenclamide and other sulfonylurea derivatives used in diabetes management increase insulin release from pancreatic β cells, leading to reduced blood glucose levels, this could be a contributing factor to its potential benefits after CNS trauma. Further experimentation is warranted to identify the mechanism (or mechanisms) and the applicability of sulfonylureas for SCI. The specialty awaits work on SUR1–TRPM4 inhibition with interest, because potent neuroprotective agents are urgently needed to improve the outcome of SCI. EJB holds a patent (0205022.7) “Materials and methods for the treatment of CNS damage”. All other authors declare no competing interests. Restoring function after spinal cord injury: towards clinical translation of experimental strategiesSpinal cord injury is currently incurable and treatment is limited to minimising secondary complications and maximising residual function by rehabilitation. Improved understanding of the pathophysiology of spinal cord injury and the factors that prevent nerve and tissue repair has fuelled a move towards more ambitious experimental treatments aimed at promoting neuroprotection, axonal regeneration, and neuroplasticity. By necessity, these new options are more invasive. However, in view of recent advances in spinal cord injury research and demand from patients, clinicians, and the scientific community to push promising experimental treatments to the clinic, momentum and optimism exist for the translation of candidate experimental treatments to clinical spinal cord injury. Full-Text PDF Sulfonylureas—a novel treatment to reduce tissue damage after acute spinal cord injury?The December issue of The Lancet Neurology features a Review article by Ramer and colleagues,1 which gives an excellent overview of best practices and promising new research directions for treatment of spinal cord injury (SCI). We would like to add the following new angle on this crucial matter: the sulfonylurea receptor 1–transient receptor potential melastatin 4 (SUR1–TRPM4) channel is upregulated within hours of SCI at the site of the lesion.2 After CNS injury, the SUR1–TRPM4 channel has been detected in neurons, astrocytes, oligodendrocytes, and microvascular endothelium at the site of injury. Full-Text PDF

Spinal cord injury is currently incurable and treatment is limited to minimising secondary complications and maximising residual function by rehabilitation. Improved understanding of the pathophysiology of spinal cord injury and the factors that prevent nerve and tissue repair has fuelled a move towards more ambitious experimental treatments aimed at promoting neuroprotection, axonal regeneration, and neuroplasticity. By necessity, these new options are more invasive. However, in view of recent advances in spinal cord injury research and demand from patients, clinicians, and the scientific community to push promising experimental treatments to the clinic, momentum and optimism exist for the translation of candidate experimental treatments to clinical spinal cord injury. The ability to rescue, reactivate, and rewire spinal systems to restore function after spinal cord injury might soon be within reach.

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.

To improve science learning, science educators' teaching tools need to address two major criteria: teaching practice should mirror our current understanding of the learning process; and science teaching should reflect scientific practice. We designed a small-group learning (SGL) model for a fourth year university neurobiology course using these criteria and studied student achievement and attitude in five course sections encompassing the transition from individual work-based to SGL course design. All students completed daily quizzes/assignments involving analysis of scientific data and the development of scientific models. Students in individual work-based (Individualistic) sections usually worked independently on these assignments, whereas SGL students completed assignments in permanent groups of six. SGL students had significantly higher final exam grades than Individualistic students. The transition to the SGL model was marked by a notable increase in 10th percentile exam grade (Individualistic: 47.5%; Initial SGL: 60%; Refined SGL: 65%), suggesting SGL enhanced achievement among the least prepared students. We also studied student achievement on paired quizzes: quizzes were first completed individually and submitted, and then completed as a group and submitted. The group quiz grade was higher than the individual quiz grade of the highest achiever in each group over the term. All students--even term high achievers--could benefit from the SGL environment. Additionally, entrance and exit surveys demonstrated student attitudes toward SGL were more positive at the end of the Refined SGL course. We assert that SGL is uniquely-positioned to promote effective learning in the science classroom.

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.

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.

Background context Individuals with high spinal cord injury (SCI) are prone to significant fluctuation in blood pressure with episodes of very high and low blood pressure during autonomic dysreflexia (AD) and orthostatic hypotension, respectively. We do not know how such blood pressure lability affects the vasculature. Purpose We used a well-characterized animal model of AD to determine whether increasing the frequency of AD during recovery from SCI would exacerbate injury-induced dysfunction in resistance vessels. Study design/setting Experimental animal study. International Collaboration On Repair Discoveries (ICORD), University of British Columbia, Canada. Methods Complete transection of the T3 spinal cord was performed in male Wistar rats. For 14 days after injury, AD was induced via colorectal distension (CRD; 30 minutes per day) in the experimental group (SCI-CRD). One month after SCI, baseline cardiovascular parameters and severity of CRD-induced AD were assessed in SCI-CRD animals and SCI-only controls. Mesenteric arteries were harvested for in vitro myography to characterize vasoactive responses to phenylephrine (PE) and acetylcholine (ACh). Results Mesenteric arteries from SCI-CRD animals exhibited larger maximal responses to PE than arteries from SCI-only controls. Hyperresponsiveness to PE was not a product of endothelial dysfunction because mesenteric arteries from both groups had similar vasodilator responses to ACh. Both SCI-only controls and SCI-CRD animals exhibited CRD-evoked AD 1 month after SCI; however, CRD-induced hypertension was less pronounced in animals that were previously exposed to CRD. Conclusions Injury-induced changes within the vasculature may contribute to the development of AD after SCI. Here, we provide evidence that AD itself has significant and long-lasting effects on vascular function. This finding has implications for the medical management of AD and provides an impetus for maintaining stable blood pressure.

The axons of dorsal root ganglion (DRG) neurons project to cutaneous and soft tissue targets in the periphery, and centrally to the spinal cord and brainstem. The peripheral process can regenerate and reconnect with targets after injury, but the central process cannot regenerate beyond the PNS–CNS

Functional re-innervation of target neurons following neurological damage such as spinal cord injury is an essential requirement of potential therapies. There are at leat two avenues by which this can be achieved: (a) through the regeneration of injured axons and (b) through promoting plasticity of those spared by the initial insult. There are several reasons why the latter approach may be more feasible, not the least of which are the inhibitory character of the glial scar, the often long distances over which injured axons must regrow, and the fact that spared axons are often already in the vicinity of denervated targets. The challenge is to unveil the well-recognized intrinsic plasticity of spared axons in a way that avoids complications, such as pain or autonomic dysfunction. One approach that we as well as others have taken is to target growth-suppressing signaling pathways initiated in spared axons by myelin-derived proteins. This article reviews models used for the study of spinal axon plasticity and describes the anatomical and behavioral effects of interfering with myelinderived proteins, their receptors, and components of their intracellular signaling cascades.

Olfactory ensheathing cells (OECs) may support axonal regrowth, and thus might be a viable treatment for spinal cord injury (SCI); however, peripherally-derived OECs remain untested in most animal models of SCI. We have transplanted OECs from the lamina propria (LP) of mice expressing green fluorescent protein (GFP) in all cell types into immunosuppressed rats with cervical or lumbar dorsal root injuries. LP-OECs were deposited into either the dorsal root ganglion (DRG), intact or injured dorsal roots, or the dorsal columns via the dorsal root entry zone (DREZ). LP-OECs injected into the DRG or dorsal root migrated centripetally, and migration was more extensive in the injured root than in the intact root. These peripherally deposited OECs migrated within the PNS but did not cross the DREZ; similarly, large- or small-caliber primary afferents were not seen to regenerate across the DREZ. LP-OEC deposition into the dorsal columns via the DREZ resulted in a laminin-rich injection track: due to the pipette trajectory, this track pierced the glia limitans at the DREZ. OECs migrated centrifugally through this track, but did not traverse the DREZ; axons entered the spinal cord via this track, but were not seen to reenter CNS tissue. We found a preferential association between CGRP-positive small- to medium-diameter afferents and OEC deposits in injured dorsal roots as well as within the spinal cord. In the cord, OEC deposition resulted in increased angiogenesis and altered astrocyte alignment. These data are the first to demonstrate interactions between sensory axons and peripherallyderived OECs following dorsal root injury. (C) 2004 whey-Liss, Inc.