How Are Neurons Eaten Alive After Motor System Injury?
When we button our jackets, reach for our coffee, or practice the violin, we rely on a remarkable system known as the corticospinal tract. This crucial pathway is responsible for orchestrating voluntary and skilled motor movements. It involves descending axons that originate in the primary motor cortex (located at the top of our brain) and travel down to the cervical spinal cord (near our neck). Unfortunately, after a cervical spinal cord injury (SCI), the corticospinal tract is often damaged, resulting in the loss of upper limb and hand function.
Our laboratory made a significant discovery regarding the consequences of corticospinal tract damage. We identified a unique form of neuronal death known as transneuronal degeneration. In this process, microglia, the innate immune cells of the central nervous system, phagocytose or "eat up" neurons that are still alive. Neurons can degenerate following an injury in areas downstream from the injury site, such as the cervical spinal cord.
Intriguingly, neuromodulation, using electrical stimulation at specific sites on the body to alter nerve activity, can prevent transneuronal degeneration. This finding suggests that maintaining neural activity through an external source can reduce neuron loss and preserve the integrity of the spinal cord motor circuit.
Microglia (green) contacting a neuron (red) after SCI
My research focuses on understanding the mechanisms of neuromodulation in the motor cortex and spinal segments and its potential to reverse the transneuronal degeneration process while improving functional outcomes after motor system injuries. I examine 1) how motor cortex neuromodulation can activate indirect cortico-brain stem-spinal pathways to promote motor function after corticospinal tract damage, 2) how increasing neural activity in spinal segments can prevent transneuronal degeneration of spinal neurons, and 3) how motor cortex and spinal segment neuromodulation can impact and prevent microglia phagocytosis of spinal neurons. I aim to advance our understanding of neuromodulation techniques and their potential for improving motor outcomes after SCI.
Identifying how neuromodulation can prevent transneuronal degeneration is promising for developing pharmacological and translational therapeutics after SCI.