Recovery of Breathing Function After Spinal Cord Injury Program
The Regenerative Physiology Laboratory's Recovery of Breathing Function After Spinal Cord Injury Program is aimed at better understanding the mechanisms underlying neural control of respiratory muscles. This research is necessary to restore the full complement of respiratory function following spinal cord injury.
Injury to the upper segments of the cervical spinal cord often results in complete or partial paralysis of respiratory muscles, including the diaphragm muscle. Impaired respiratory muscle function frequently requires ventilatory support for patients and is associated with higher morbidity and mortality rates.
Ongoing research in the Regenerative Physiology Lab uses new information on the mechanisms underlying recovery of respiratory function to explore novel therapies for patients with spinal cord injury.
Dr. Mantilla's team showed that recovery of diaphragm muscle activity is enhanced by promoting the effect of brain-derived neurotrophic factor (BDNF) at phrenic motor neurons. For example, intrathecal BDNF treatment enhances functional recovery of rhythmic diaphragm muscle activity after spinal cord injury.
Unfortunately, intrathecal BDNF treatment is associated with significant negative adverse effects that preclude its therapeutic use. As an alternative, the lab's recent studies used locally implanted mesenchymal stem cells that are genetically engineered to produce BDNF, combined with a novel targeted approach to increase expression of tropomyosin related kinase receptor (TrkB) in phrenic motor neurons using an adeno-associated virus, thereby promoting functional recovery after spinal cord injury.
Current research: Recovery of Respiratory Function After Spinal Cord Injury Project
The lab's Recovery of Respiratory Function After Spinal Cord Injury Project exploits exciting new developments in neuroplasticity to enhance recovery of respiratory function following cervical spinal cord injury (SCI).
There are about 12,000 new cases of SCI in the U.S. each year, with nearly 500,000 people affected in total. Most SCIs are incomplete, with some sparing of spinal cord pathways. The number of injuries involving the cervical spinal cord is increasing, with resulting impairments of rhythmic phrenic nerve activity and paralysis of the diaphragm muscle.
The lab's working hypothesis is that increasing brain-derived neurotrophic factor-tropomyosin related kinase receptor (BDNF-TrkB) signaling in phrenic motor neurons enhances functional recovery of rhythmic phrenic activity after cervical SCI. Dr. Mantilla's research team is assessing phrenic responses across a range of motor behaviors to maximize functional gains associated with recovery.
The Recovery of Respiratory Function After Spinal Cord Injury Project takes a multipronged approach to gain mechanistic insight into the effects of BDNF-TrkB signaling on strengthening spared synaptic inputs to phrenic motor neurons and enhancing motor neuron survival post-SCI.
The lab's long-term goal is to develop an effective, targeted therapy to increase BDNF-TrkB signaling in phrenic motor neurons to strengthen spared synaptic inputs to phrenic motoneurons and promote motoneuron survival, thereby enhancing functional recovery following SCI.