Functional Recovery After Cervical Spinal Cord Injury
Upper cervical spinal cord injury often results in complete or partial diaphragm muscle paralysis that may require ventilatory support for patients and is associated with higher morbidity and mortality rates. It is important to understand how rhythmic diaphragm muscle activity can be restored in patients with spinal cord injury.
Dr. Sieck's research team has shown that at the level of phrenic motor neurons, functional recovery of diaphragm muscle activity is enhanced by promoting the effect of brain-derived neurotrophic factor (BDNF) acting through TrkB. 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 Cell and Regenerative Physiology Lab is exploring the use of locally implanted mesenchymal stem cells that are genetically engineered to produce BDNF. Dr. Sieck's team also has developed a novel targeted approach to increase TrkB expression in phrenic motor neurons using an adeno-associated virus and thereby promoting functional recovery after spinal cord injury.