AIH for Spinal Cord Repair
| Status: | Not yet recruiting |
|---|---|
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 12/21/2018 |
| Start Date: | July 1, 2019 |
| End Date: | March 31, 2023 |
| Contact: | Monica A Perez, PhD |
| Email: | perezmo@miami.edu |
| Phone: | (412) 383-6563 |
Repetitive Acute Intermittent Hypoxia for Spinal Cord Repair
Contusive cervical spinal cord injury (cSCI) impairs upper limb function (reach-and-grasp)
which limits daily-life activities and thus decreases the quality of life. Promoting
neuroplasticity may support upper limb recovery after SCI. Repetitive exposure to acute
intermittent hypoxia (rAIH) combined with motor training promotes recovery of motor function
after SCI; however, the overall effects of rAIH/training are limited. The investigators will
use an adult rat model of long-term contusive cSCI to study novel approaches to enhance the
effect of rAIH/training on forelimb function and study the neuronal substrate underlying the
effects. The findings will be used to direct the development of more effective rAIH/training
approaches for people with contusive, functionally incomplete, cSCI. Because deficits in
upper limb function are a major problem after stroke, amyotrophic lateral sclerosis, multiple
sclerosis, and other motor disorders, this work may also be relevant for patients with other
types of central nervous system (CNS) lesions.
which limits daily-life activities and thus decreases the quality of life. Promoting
neuroplasticity may support upper limb recovery after SCI. Repetitive exposure to acute
intermittent hypoxia (rAIH) combined with motor training promotes recovery of motor function
after SCI; however, the overall effects of rAIH/training are limited. The investigators will
use an adult rat model of long-term contusive cSCI to study novel approaches to enhance the
effect of rAIH/training on forelimb function and study the neuronal substrate underlying the
effects. The findings will be used to direct the development of more effective rAIH/training
approaches for people with contusive, functionally incomplete, cSCI. Because deficits in
upper limb function are a major problem after stroke, amyotrophic lateral sclerosis, multiple
sclerosis, and other motor disorders, this work may also be relevant for patients with other
types of central nervous system (CNS) lesions.
The overall goal is to develop effective, clinically applicable, approaches to restore upper
limb function (reach-and-grasp) after chronic contusive cervical spinal cord injury (cSCI).
Impairments in upper limb function significantly reduce the quality of life for people with
cSCI. Reach-and-grasp actions in animals and humans are largely controlled by the
corticospinal tract (CST). The investigators argue that promoting plasticity within the CST
may support the recovery of upper limb function after cSCI. Repetitive exposure to acute
intermittent hypoxia (rAIH) combined with motor training is a safe, minimally invasive,
treatment that elicits neuroplasticity resulting in improved recovery after cSCI, but its
overall effects remain limited. The main goals are to: 1) enhance rAIH/training-induced
aftereffects on forelimb function and increase the understanding of the neuronal substrates
in an adult rat model of chronic contusive cSCI, and 2) use this knowledge to guide the
development of more effective rAIH/training approaches to improve upper limb function in
humans with chronic contusive cSCI.
In Specific Aim 1, using an adult rat model of chronic contusive cSCI, the investigators will
investigate the effects of rAIH frequency and dose on rAIH/training-mediated functional
recovery of the impaired forelimb. Also, the investigators will combine rAIH/training with
N-methyl-D-aspartate receptor (NMDA)-mediated synaptic plasticity through D-cycloserine
treatment and study the effects on recovery of forelimb function. Immunocytochemistry with
imaging techniques will be used to assess structural neuronal plasticity in the CST after
rAIH/training. In Specific Aim 2, in people with chronic incomplete cSCI, guided by the
findings in Specific Aim 1, the investigators will study the effects of rAIH frequency and
concurrent D-cycloserine treatment on rAIH/training-mediated upper limb function recovery.
The investigators will comprehensively analyze the effects of rAIH on the strength of
electrophysiological and functional aftereffects in the upper limb.
The proposed research will provide new knowledge on rAIH/training-mediated functional and
anatomical aftereffects (Specific Aim 1), which will be used to develop effective
rAIH/training protocols for people with contusive, functionally incomplete, cSCI (Specific
Aim 2). The data from the investigators' experiments may lead to clinically applicable
approaches that improve arm and hand function recovery after chronic contusive cSCI, which
would positively impact the quality of life of Veterans with cSCI. The relevance of this
proposal is emphasized by the limited efficacy of current strategies to improve upper limb
function after cSCI.
limb function (reach-and-grasp) after chronic contusive cervical spinal cord injury (cSCI).
Impairments in upper limb function significantly reduce the quality of life for people with
cSCI. Reach-and-grasp actions in animals and humans are largely controlled by the
corticospinal tract (CST). The investigators argue that promoting plasticity within the CST
may support the recovery of upper limb function after cSCI. Repetitive exposure to acute
intermittent hypoxia (rAIH) combined with motor training is a safe, minimally invasive,
treatment that elicits neuroplasticity resulting in improved recovery after cSCI, but its
overall effects remain limited. The main goals are to: 1) enhance rAIH/training-induced
aftereffects on forelimb function and increase the understanding of the neuronal substrates
in an adult rat model of chronic contusive cSCI, and 2) use this knowledge to guide the
development of more effective rAIH/training approaches to improve upper limb function in
humans with chronic contusive cSCI.
In Specific Aim 1, using an adult rat model of chronic contusive cSCI, the investigators will
investigate the effects of rAIH frequency and dose on rAIH/training-mediated functional
recovery of the impaired forelimb. Also, the investigators will combine rAIH/training with
N-methyl-D-aspartate receptor (NMDA)-mediated synaptic plasticity through D-cycloserine
treatment and study the effects on recovery of forelimb function. Immunocytochemistry with
imaging techniques will be used to assess structural neuronal plasticity in the CST after
rAIH/training. In Specific Aim 2, in people with chronic incomplete cSCI, guided by the
findings in Specific Aim 1, the investigators will study the effects of rAIH frequency and
concurrent D-cycloserine treatment on rAIH/training-mediated upper limb function recovery.
The investigators will comprehensively analyze the effects of rAIH on the strength of
electrophysiological and functional aftereffects in the upper limb.
The proposed research will provide new knowledge on rAIH/training-mediated functional and
anatomical aftereffects (Specific Aim 1), which will be used to develop effective
rAIH/training protocols for people with contusive, functionally incomplete, cSCI (Specific
Aim 2). The data from the investigators' experiments may lead to clinically applicable
approaches that improve arm and hand function recovery after chronic contusive cSCI, which
would positively impact the quality of life of Veterans with cSCI. The relevance of this
proposal is emphasized by the limited efficacy of current strategies to improve upper limb
function after cSCI.
Inclusion Criteria:
- Male and females Veterans between 18-80 years
- Chronic cSCI (1 yr of injury)
- Cervical injury at C8 or above
- Sensory function: impaired (score of 1) but not absent (score of 0) or intact (score
of 2) innervations in dermatomes C6, C7 and C8 during light touch and pin prick
stimulus using the International Standards for Neurological Classification of Spinal
Cord Injury (ISNCSCI) sensory scores
- Motor function: Able to grasp small objects with one hand and able to perform a
visible precision grasp between the index finger and thumb
- Motor scores ISNCSCI: 1 to 4 but not 5 on finger flexors and finger abductors on the
hand tested.
- These criteria were selected to ensure that hand impairment will not interfere
with the ability to perform training and proposed tests
Inclusion criteria for controls:
- Male and females (18-80 years)
- Right handed
- Able to complete precision and power grips
Exclusion Criteria:
- Uncontrolled medical problems including pulmonary, cardiovascular or orthopedic
disease
- Any debilitating disease prior to the SCI that caused exercise intolerance
- Premorbid, ongoing major depression or psychosis, altered cognitive status
- History of head injury or stroke
- Pacemaker
- Metal plate in skull
- History of seizures
- Receiving drugs acting primarily on the central nervous system, which lower the
seizure threshold such as antipsychotic drugs
- chlorpromazine
- clozapine
- or tricyclic antidepressants
- Pregnant females
- Ongoing cord compression or a syrinx in the spinal cord or who suffer from a spinal
cord disease as spinal stenosis, spina bifida or herniated cervical disk
- Presence of autonomic dysreflexia
Exclusion criteria for healthy controls:
- Same as for SCI individuals
We found this trial at
1
site
Miami, Florida 33125
Principal Investigator: Martin Oudega, PhD
Phone: 412-383-6563
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