Inability to maintain upright body posture and equilibrium is one of the major motor disorders following traumatic spinal cord injury (SCI). In our previous, NIH-supported studies, impairment and recovery of postural functions after SCI were characterized in an animal model (rabbit). A general goal of the present project is to explain these phenomena on the basis of SCI-caused changes in the operation of the corresponding neuronal postural mechanisms (networks). Complete SCI abolishes all brain influences on the spinal cord, which results in spinal shock (a dramatic decrease of muscle tone and spinal reflexes).
Our Aim 1 is to analyze the effect of complete SCI on the operation of spinal postural networks, and to explain spinal shock by the changes in activity of specific groups of spinal neurons. We have developed a novel technique for studying neuronal mechanisms of spinal shock. Cooling the spinal cord at T12 causes a temporary blockade of signal transmission in spinal pathways - "reversible spinalization", which can be done repeatedly many times. This allows studying postural responses and activity of individual spinal neurons under two conditions: (i) when the spinal cord is connected with the brain, and (ii) during spinal shock, when the spinal cord is temporarily disconnected from the brain. Spinal shock is followed by a period of gradually developing spasticity (including abnormal reflex responsiveness, clonus, and hypertonus).
Our Aim 2 is to analyze activity of spinal postural networks during this period, and to explain the development of different aspects of spasticity by the changes in activity of specific groups of spinal neurons. For this purpose, we will (i) record postural reflexes and activity of individual spinal neurons at different stages of spasticity, and (ii) correlate the changes in neuronal activity with the changes in postural performance. Previously we have shown that, after incomplete SCI (lateral hemisection), postural functions recover in a few weeks.
Our Aim 3 is to reveal the contribution of plastic changes in the spinal and supraspinal mechanisms to functional recovery. This will be done by comparing postural reflexes and activity of individual spinal neurons in animals at different degrees of compensation (i) before and (ii) during the cold block of spinal pathways on the undamaged side. This study will provide unique information about the SCI-caused changes in the activity of spinal neuronal networks, which are responsible for the motor deficits, as well as about the changes underlying functional recovery in subjects with incomplete SCI. This information is clinically relevant as a basis for designing new rehabilitation strategies in SCI subjects. These strategies can be focused on restoration of normal activity in specific groups of spinal neurons.

Public Health Relevance

Spinal cord injury (SCI) results in severe damage of the nervous control of posture and balance, and the patients are bound to a wheel chair. Their rehabilitation constitutes both clinical and social problems. The present project will contribute to development of rehabilitation strategies aimed at restoration of postural and other motor functions after SCI.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS064964-02
Application #
8286750
Study Section
Acute Neural Injury and Epilepsy Study Section (ANIE)
Program Officer
Ludwig, Kip A
Project Start
2011-07-01
Project End
2013-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
2
Fiscal Year
2012
Total Cost
$240,491
Indirect Cost
$17,814
Name
Karolinska Institute
Department
Type
DUNS #
350582235
City
Stockholm
State
Country
Sweden
Zip Code
171 7-7
Musienko, Pavel E; Deliagina, Tatiana G; Gerasimenko, Yury P et al. (2014) Limb and trunk mechanisms for balance control during locomotion in quadrupeds. J Neurosci 34:5704-16
Zelenin, P V; Hsu, L-J; Orlovsky, G N et al. (2012) Use of galvanic vestibular feedback to control postural orientation in decerebrate rabbits. J Neurophysiol 107:3020-6
Hsu, L-J; Zelenin, P V; Orlovsky, G N et al. (2012) Effects of galvanic vestibular stimulation on postural limb reflexes and neurons of spinal postural network. J Neurophysiol 108:300-13