Trigger mechanism for recovery after spinal cord injury identified.


After an incomplete spinal cord injury, the body can partially recover basic motor function. So-called muscle spindles and associated sensory circuits back to the spinal chord promote the establishment of novel neuronal connections after injury. This circuit-level mechanism behind the process of motor recovery was identified by researchers from the University of Basel, EPFL and the Friedrich Miescher Institute. Their findings may contribute to designing novel strategies for treatment after spinal cord injuries.  The opensource study has been published in the journal Cell.

Spinal cord injuries often lead to chronically impaired motor function. However, patients with incomplete spinal cord injury can partially regain their basic motor ability under certain circumstances. It is believed that remaining uninjured spinal cord tissue provides a substrate to form new circuits bridging the injury. How this formation of new connections is triggered and promoted has remained unclear until now.

The team demonstrated in a mouse model why paralyzed limbs can move again after incomplete spinal cord injuries.  A specific sensory feedback channel connected to sensors embedded within the muscles, so-called muscle spindles, promotes the functional recovery of the damaged neuronal circuits in the spinal cord.

Muscle spindles are sensors in the skeletal muscles of the body, which are passively stretched or shortened by muscle expansion and contraction. Each of these muscle spindles, localized within a muscle, is contacted by sensory nerves. Sensory information is conveyed by these neurons directly from the muscles (e.g. from the arms or legs) back to the spinal cord. These transmitted impulses allow humans, for example, to determine with closed eyes in which position their arms, legs, hands, and fingers are. In other words, to know where their whole body is positioned.

The team observed that limb movement activates sensory feedback loops from the muscle to the spinal cord. This specific feedback channel promotes the repair process of the damaged spinal network after injury. As a result, basic motor function can be restored.  The team state that the sensory feedback loops from muscle spindles are therefore a key factor in the recovery process. After spinal cord injury, these nerve impulses keep providing information to the central nervous system, even when the transmission of information from the brain to the spinal cord no longer functions.

An important trigger for the recovery process is the information conveyed from the muscle to the central nervous system and not only the top-down information the brain sends towards muscles.  In addition, the researchers demonstrated that only basic locomotor functionality could be restored spontaneously after an injury. Fine locomotor task performance tested, however, remained permanently lost.

The study suggests that activation of muscle spindles is essential to promote the recovery process of damaged neuronal networks after spinal cord injury. Thus, therapeutic approaches should aim to extensively use the muscles, even if passively after an injury. The more intensely muscles are used in the movement process, the more muscle spindle feedback circuits are stimulated. By applying this principle, the repair of neuronal circuits and the accompanying recovery of basic motor skills will have the best chances of succeeding.

Source:  University of Basel

 

Spinal cord injuries alter motor function by disconnecting neural circuits above and below the lesion, rendering sensory inputs a primary source of direct external drive to neuronal networks caudal to the injury. Here, we studied mice lacking functional muscle spindle feedback to determine the role of this sensory channel in gait control and locomotor recovery after spinal cord injury. High-resolution kinematic analysis of intact mutant mice revealed proficient execution in basic locomotor tasks but poor performance in a precision task. After injury, wild-type mice spontaneously recovered basic locomotor function, whereas mice with deficient muscle spindle feedback failed to regain control over the hindlimb on the lesioned side. Virus-mediated tracing demonstrated that mutant mice exhibit defective rearrangements of descending circuits projecting to deprived spinal segments during recovery. Our findings reveal an essential role for muscle spindle feedback in directing basic locomotor recovery and facilitating circuit reorganization after spinal cord injury.   Muscle Spindle Feedback Directs Locomotor Recovery and Circuit Reorganization after Spinal Cord Injury.  Arber et al 2014.

Spinal cord injuries alter motor function by disconnecting neural circuits above and below the lesion, rendering sensory inputs a primary source of direct external drive to neuronal networks caudal to the injury. Here, we studied mice lacking functional muscle spindle feedback to determine the role of this sensory channel in gait control and locomotor recovery after spinal cord injury. High-resolution kinematic analysis of intact mutant mice revealed proficient execution in basic locomotor tasks but poor performance in a precision task. After injury, wild-type mice spontaneously recovered basic locomotor function, whereas mice with deficient muscle spindle feedback failed to regain control over the hindlimb on the lesioned side. Virus-mediated tracing demonstrated that mutant mice exhibit defective rearrangements of descending circuits projecting to deprived spinal segments during recovery. Our findings reveal an essential role for muscle spindle feedback in directing basic locomotor recovery and facilitating circuit reorganization after spinal cord injury. Muscle Spindle Feedback Directs Locomotor Recovery and Circuit Reorganization after Spinal Cord Injury. Arber et al 2014.

 

 

 

 

 

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