Noninvasive Neuroprosthesis Promotes Cardiovascular Recovery After Spinal Cord Injury.

Spinal cord injury (SCI) leads to severe impairment in cardiovascular control, commonly manifested as a rapid, uncontrolled rise in blood pressure triggered by peripheral stimuli-a condition called autonomic dysreflexia. The objective was to demonstrate the translational potential of noninvasive transcutaneous stimulation (TCS) in mitigating autonomic dysreflexia following SCI, using pre-clinical evidence and a clinical case report. In rats with SCI, we show that TCS not only prevents the instigation of autonomic dysreflexia, but also mitigates its severity when delivered during an already-triggered episode. Furthermore, when TCS was delivered as a multisession therapy for 6 weeks post-SCI, the severity of autonomic dysreflexia was significantly reduced when tested in the absence of concurrent TCS. This treatment effect persisted for at least 1 week after the end of therapy. More importantly, we demonstrate the clinical applicability of TCS in treatment of autonomic dysreflexia in an individual with cervical, motor-complete, chronic SCI. We anticipate that TCS will offer significant therapeutic advantages, such as obviating the need for surgery resulting in reduced risk and medical expenses. Furthermore, this study provides a framework for testing the potential of TCS in improving recovery of other autonomic functions such lower urinary tract, bowel, and sexual dysfunction following SCI.

The Therapeutic Potential and Usage Patterns of Cannabinoids in People with Spinal Cord Injuries: A Systematic Review.

BACKGROUND: People with spinal cord injuries (SCI) commonly experience pain and spasticity; limitations of current treatments have generated interest in cannabis as a possible therapy. OBJECTIVES: We conducted this systematic review to: 1) examine usage patterns and reasons for cannabinoid use, and 2) determine the treatment efficacy and safety of cannabinoid use in people with SCI. METHODS: PubMed, Embase, Web of Science and Cumulative Index to Nursing and Allied Health Literature databases were queried for keywords related to SCI and cannabinoids. RESULTS: 7,232 studies were screened, and 34 were included in this systematic review. Though 26 studies addressed cannabinoid usage, only 8 investigated its therapeutic potential on outcomes such as pain and spasticity. The most common method of use was smoking. Relief of pain, spasticity and recreation were the most common reasons for use. A statistically significant reduction of pain and spasticity was observed with cannabinoid use in 83% and 100% of experimental studies, respectively. However, on examination of randomized control trials (RCTs) alone, effect sizes ranged from - 0.82 to 0.83 for pain and -0.95 to 0.09 for spasticity. Cannabinoid use was associated with fatigue and cognitive deficits. CONCLUSION: Current evidence suggests that cannabinoids may reduce pain and spasticity in people with SCI, but its effect magnitude and clinical significance are unclear. Existing information is lacking on optimal dosage, method of use, composition and concentration of compounds. Long-term, double-blind, RCTs, assessing a wider range of outcomes should be conducted to further understand the effects of cannabinoid use in people with SCI.

Cerebrovascular function is preserved during mild hyperthermia in cervical spinal cord injury.

STUDY DESIGN: Experimental study. OBJECTIVES: Compromised cerebrovascular function likely contributes to elevated neurological risk in spinal cord injury (SCI). Passive heating offers many cardiovascular and neurological health benefits; therefore, we aimed to determine the effects of an acute bout of heating on cerebrovascular function in chronic SCI. METHODS: Persons with cervical SCI (n = 15) and uninjured controls (CON; n = 15) completed 60 min of lower limb hot water immersion (40 °C). Assessments of middle cerebral (MCA) and posterior cerebral artery (PCA) velocities, pulsatilities, and neurovascular coupling (NVC) were performed using transcranial Doppler ultrasound. Duplex ultrasonography was used to index cerebral blood flow via the internal carotid artery (ICA), and carotid-femoral pulse-wave velocity (PWV) was measured using tonometry. The NVC response was quantified as the peak hyperemic value during 30-s cycles of visual stimulation. RESULTS: Mean arterial pressure changed differentially with heating [mean (standard deviation); SCI: +6(14) mmHg, CON: -8(12) mmHg; P = 0.01]. There were no differences in any intracranial artery measures (all P > 0.05), except for small (~10%) increases in MCA conductance in CON after heating vs. SCI (interaction P = 0.006). Resting ICA flow was greater in SCI vs. CON (P = 0.03) but did not change with heating in either group (interaction P = 0.34). There were also no between-group differences in the NVC response (ΔPCA conductance) pre- [SCI: 29(19)% vs. CON: 30(9)%] or post-heating [SCI 30(9)% vs. 25(9)%; interaction P = 0.22]. CONCLUSIONS: Mild acute heating does not impair or improve cerebrovascular function in SCI or CON. Thus, further study of the effects of chronic heating interventions are warranted.

Acute heat stress reduces biomarkers of endothelial activation but not macro- or microvascular dysfunction in cervical spinal cord injury.

Cardiovascular diseases (CVD) are highly prevalent in spinal cord injury (SCI), and peripheral vascular dysfunction might be a contributing factor. Recent evidence demonstrates that exposure to heat stress can improve vascular function and reduce the risk of CVD in uninjured populations. We therefore aimed to examine the extent of vascular dysfunction in SCI and the acute effects of passive heating. Fifteen participants with cervical SCI and 15 uninjured control (CON) participants underwent ultrasound assessments of vascular function and venous blood sampling for biomarkers of endothelial activation (i.e., CD62e+) and apoptosis (i.e., CD31+/42b-) before and after a 60-min exposure to lower limb hot water immersion (40°C). In SCI, macrovascular endothelial function was reduced in the brachial artery [SCI: 4.8 (3.2)% vs. CON: 7.6 (3.4)%, P = 0.04] but not the femoral artery [SCI: 3.7 (2.6)% vs. CON: 4.0 (2.1)%, P = 0.70]. Microvascular function, via reactive hyperemia, was ~40% lower in SCI versus CON in both the femoral and brachial arteries ( P < 0.01). Circulating concentrations of CD62e+ were elevated in SCI versus CON [SCI: 152 (106) microparticles/µl vs. CON: 58 (24) microparticles/µl, P < 0.05]. In response to heating, macrovascular and microvascular function remained unchanged, whereas increases (+83%) and decreases (-93%) in antegrade and retrograde shear rates, respectively, were associated with heat-induced reductions of CD62e+ concentrations in SCI to levels similar to CON ( P = 0.05). These data highlight the potential of acute heating to provide a safe and practical strategy to improve vascular function in SCI. The chronic effects of controlled heating warrant long-term testing. NEW & NOTEWORTHY Individuals with cervical level spinal cord injury exhibit selectively lower flow-mediated dilation in the brachial but not femoral artery, whereas peak reactive hyperemia was lower in both arteries compared with uninjured controls. After 60 min of lower limb hot water immersion, femoral artery blood flow and shear patterns were acutely improved in both groups. Elevated biomarkers of endothelial activation in the spinal cord injury group decreased with heating, but these biomarkers remained unchanged in controls.

Respiratory Training Improves Blood Pressure Regulation in Individuals With Chronic Spinal Cord Injury.

OBJECTIVE: To investigate the effects of respiratory motor training (RMT) on pulmonary function and orthostatic stress-mediated cardiovascular and autonomic responses in individuals with chronic spinal cord injury (SCI). DESIGN: Before-after intervention case-controlled clinical study. SETTING: SCI research center and outpatient rehabilitation unit. PARTICIPANTS: A sample of (N=21) individuals with chronic SCI ranging from C3 to T2 diagnosed with orthostatic hypotension (OH) (n=11) and healthy, noninjured controls (n=10). INTERVENTIONS: A total of 21±2 sessions of pressure threshold inspiratory-expiratory RMT performed 5d/wk during a 1-month period. MAIN OUTCOME MEASURES: Standard pulmonary function test: forced vital capacity, forced expiratory volume in one second, maximal inspiratory pressure, maximal expiratory pressure, beat-to-beat arterial blood pressure, heart rate, and respiratory rate were acquired during the orthostatic sit-up stress test before and after the RMT program. RESULTS: Completion of RMT intervention abolished OH in 7 of 11 individuals. Forced vital capacity, low-frequency component of power spectral density of blood pressure and heart rate oscillations, baroreflex effectiveness, and cross-correlations between blood pressure, heart rate, and respiratory rate during the orthostatic challenge were significantly improved, approaching levels observed in noninjured individuals. These findings indicate increased sympathetic activation and baroreflex effectiveness in association with improved respiratory-cardiovascular interactions in response to the sudden decrease in blood pressure. CONCLUSIONS: Respiratory training increases respiratory capacity and improves orthostatic stress-mediated respiratory, cardiovascular, and autonomic responses, suggesting that this intervention can be an efficacious therapy for managing OH after SCI.

Response to functional electrical stimulation cycling in women with spinal cord injuries using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography: a case series.

BACKGROUND: Loss of bone mass is common after spinal cord injury (SCI). One rehabilitation modality that has shown some promise for maintaining bone health is the functional electrical stimulation (FES) cycle ergometer. Although there has been some research investigating bone health and FES cycle ergometry, few have provided a detailed description of the changes that can occur in bone mass and soft-tissue mass. OBJECTIVE: To use 2 types of bone imaging, peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), to provide a detailed description of bone and soft-tissue response to FES cycle ergometry training in women with SCI. STUDY DESIGN: Case series; a 6-month program of FES cycle ergometry for women with chronic motor complete (n = 2) and incomplete (n = 1) SCI. SETTING: Outpatient rehabilitation center in Canada. METHODS: Three women participated in a thrice weekly 6-month exercise program of FES cycle ergometry. We used DXA (lower extremity) and pQCT at the midshaft (50%) and distal (5%) sites of the tibia to assess bone density and soft-tissue mass before and after the exercise program. RESULTS: There was an increase or maintenance in bone mineral density by DXA and pQCT in the lower extremity for all 3 participants. Muscle mass by DXA increased in the lower extremity in 2 participants. CONCLUSION: In this case series, we note a positive response in bone mass and soft-tissue mass in the lower extremity after a 6-month FES cycle ergometry program.

Screening and habituation of functional electrical stimulation-leg cycle ergometry for individuals with spinal cord injury: a pilot study.

OBJECTIVES: To document the screening process and develop the habituation procedures prior to commencing a functional electrical stimulation leg cycle ergometry (FES-LCE) exercise program for individuals with spinal cord injury (SCI). DESIGN: This was a prospective descriptive study of screening and habituation for FES-LCE exercise for people with chronic SCI (injury duration longer than one year). SETTING: : Tertiary rehabilitation center. PARTICIPANTS: Thirteen subjects with SCI (mean years since injury, 7; mean age, 34.8 years; injury range, C4-T10; 7 males). MAIN OUTCOME MEASURES: Time to attain target cycle speed for 30 continuous minutes. RESULTS: Six of the 13 subjects were not eligible to start the FES-LCE habituation program because of previous fragility fracture, excessive spasticity, pain, autonomic dysreflexia, or lack of electrical stimulation response because of lower motor neuron damage in individuals with low thoracic injuries (T11-12). Time to attain target cycle speed for 30 continuous minutes ranged from 30 to 779 minutes (1-31 training sessions). CONCLUSIONS: Almost half of the individuals interested in participating in the FES-LCE exercise program did not pass the screening phase. Although the habituation phase was time-consuming for most of the participants who were able to use the FES-LCE, all reported few adverse effects to using the device once they completed this phase of training.

An in vitro model of neurotrauma in organotypic spinal cord cultures from adult mice.

Cellular degeneration after spinal cord injury (SCI) involves numerous pathways. It is essential to use appropriate experimental models in order to understand the complex processes, which evolve after the initial trauma. The purpose of this study was to develop and assess an in vitro model of neurotrauma using organotypic slice culture of adult mice spinal cord. This model will facilitate the investigation of primary and secondary mechanisms of cell death that occurs after SCI. We modified previously described methods for generating organotypic cultures of murine spinal cord. The viability of organotypic cultures was assessed by observing the outgrowth of neurites and by using a mitochondria dependent dye for live cells (tetrazolium dye; MTT). The morphological integrity of cultures was examined histologically by hematoxylin and eosin (H&E) staining for general morphology and with luxol fast blue (LFB) for myelin. Neuronal and glial (GFAP; CNPase) markers were used to identify neurons, astrocytes and oligodendroglia, respectively. Primary injury was achieved by using a weight drop (0.2 g) model of injury. Cell death after primary injury was attenuated by pre-treatment with two known neuroprotective agents: the AMPA/KA blocker CNQX and methylprednisolone. The nuclear markers Propidium iodide and Sytox-green, as well as the TUNEL (in situ terminal deoxytransferase-mediated dUTP nick end labeling) technique, were used as a quantitative indicators of cell death at 24, 48 and 72 h post-injury using a confocal microscope and image analysis software. This novel in vitro model of SCI is easy to reproduce, will facilitate the examination of post-trauma cell death mechanisms and the neuroprotective effects of pharmacological agents and aid in the study of transgenic murine models.