Effects of Remote Ischemic Conditioning on Hand Use in Individuals With Spinal Cord Injury

Most spinal cord injuries (SCI) are not full transections, indicating that there are residual
nerve circuits after injury. Rehabilitation interventions after SCI, including physical
training and neural stimulation, have been shown to reorganize motor pathways in the brain,
corticospinal tract (CST), and at the spinal level; a process called neural plasticity.
Functional improvement due to neural plasticity after SCI could be from enhanced excitability
of residual neural circuits, or axon sprouting which has been shown in animal studies.
However, both physical training and neural stimulation require a large number of repetitions,
and the retention of the intervention effects may be fleeting. Therefore, the need remains
for an effective approach to synergistically improve neuroplasticity in combination with
other interventions. Remote ischemic conditioning (RIC) has been shown to promote neural
plasticity and may have practical and theoretical advantages, which include: 1) RIC requires
minimal equipment, (a timer and a manual blood pressure device); and 2) RIC has been shown to
promote Hypoxia-inducible factor 1a (HIF-1a) and anti-inflammatory mediators which possibly
promote neuroplasticity. In fact, One recent study has demonstrated in able-bodied subjects
that introducing RIC before a motor learning intervention had a greater and longer-lasting
effect on improving motor performance compared to sham conditioning prior to motor learning.
In this proposed study, the investigators will investigate RIC coupled with physical training
to promote neuroplasticity in hand muscles after cervical SCI. This will be the first study
to introduce RIC in SCI population. The investigators hypothesize that RIC will acutely
synergize with motor task training via increasing corticospinal excitability. Identifying the
underlying mechanisms responsible for increasing corticospinal excitability, such as 1)
increased cortical firing, 2) strengthened synaptic transmission, 3) improved spinal motor
neuron recruitment or 4) other mechanisms is an important step for promotion of functional
recovery after neurological injury. Aim 1: To determine the effects of active versus sham RIC
prior to one bout of muscle contraction exercise on motor corticospinal excitability at the
abductor pollicis brevis (APB) muscle. The investigators will also assess intra-cortical
facilitation/inhibition and peripheral nerve conduction profiles to localize the level of
changes in corticospinal excitability. Aim 2: To investigate effects of active versus sham
RIC on systemic inflammatory mediators in individuals with SCI. Individuals living with SCI
often show signs of chronic inflammation and other aspects of dysregulated immune system
function. Studies in able-bodied adults have shown that a single application of RIC can
suppress inflammatory gene expression in circulating leukocytes 15 min and 24h later.
Upregulation of inflammatory cytokines is associated with decreased expression of genes that
promote neuroplasticity, such as BDNF. Here, the investigators will determine if RIC
decreases systemic inflammation in persons with chronic SCI, as it does in able-bodied
individuals, by measuring a subset of inflammatory mediators in the blood pre- and post-RIC.
Aim 3: To determine changes in heart rate (HR), blood pressure (BP) and oxygen saturation
(SaO2) during active versus sham RIC in individuals with incomplete cSCI and able-bodied
subjects. RIC has been shown to be safe in the healthy population as well as in individuals
with heart disease and even critically ill patients with subarachnoid hemorrhage. However,
there are no data describing the safety of RIC in persons with SCI. Damage to the autonomic
nervous system (ANS) contributes to cardiovascular dysregulation and may alter physiological
responses to RIC. In addition, the SCI population, particularly those with cervical SCI, has
widespread sensory impairment, including a limited ability to feel pain/discomfort. The
investigators will not only real-time record HR, BP and SaO2 responses during RIC, but also
document the pain scale and any adverse effects of RIC in individuals with cSCI and
able-bodied subjects.

Able-bodied participants

1. Age between 18 and 65 years;

2. No known central or peripheral neurological disease or injury.

SCI participants

Inclusion Criteria:

1. Age between 18 and 65 years;

2. Chronic (more than 12 months since injury) motor-incomplete SCI between neurological
levels C2-C8

3. Detectable F-wave responses of the left or right abductor pollicis brevis (APB) to
median nerve stimulation;

4. Detectable motor evoked potentials in left or right APB muscles to transcranial
magnetic stimulation;

5. Able to perform thumb-middle finger opposition pinch task with detectable APB EMG
muscle activity.

Exclusion Criteria:

1. Multiple spinal cord lesions;

2. History of seizures;

3. Use of medications that significantly lower seizure threshold, such as amphetamines
and bupropion;

4. History of implanted brain/spine/nerve stimulators, aneurysm clips, or cardiac
pacemaker/defibrillator;

5. Any extremity soft tissue, orthopedic, or vascular condition or injury that may
contraindicate RLIC (uncontrolled hypertension, peripheral vascular disease,
hematological disease, severe hepatic or renal dysfunction);

6. Any other contraindication to undergoing magnetic resonance imaging (except for
claustrophobia);

7. Clinically significant infection of any kind (urinary tract, pulmonary, skin or other)

8. Significant coronary artery or cardiac conduction disease;

9. Open skin lesions over the neck, shoulders, or arms;

10. Pregnancy

11. Unsuitable for study participation as determined by study physician. In addition, a
medical record review will be conducted to identify any other medical concerns that
might increase the risks associated with participation.