Cardiovascular dysfunction following spinal cord injury

Both sensorimotor and autonomic dysfunctions often occur after spinal cord injury（SCI）. Particularly, a high thoracic or cervical SCI interrupts supraspinal vasomotor pathways and results in disordered hemodynamics due to deregulated sympathetic outflow. As a result of the reduced sympathetic activity, patients with SCI may experience hypotension, cardiac dysrhythmias, and hypothermia post-injury. In the chronic phase, changes within the CNS and blood vessels lead to orthostatic hypotension and life-threatening autonomic dysreflexia（AD）. AD is characterized by an episodic, massive sympathetic discharge that causes severe hypertension associated with bradycardia. The syndrome is often triggered by unpleasant visceral or sensory stimuli below the injury level. Currently the only treatments are palliative - once a stimulus elicits AD, pharmacological vasodilators are administered to help reduce the spike in arterial blood pressure. However, a more effective means would be to mitigate AD development by attenuating contributing mechanisms, such as the reorganization of intraspinal circuits below the level of injury. A better understanding of the neuropathophysiology underlying cardiovascular dysfunction after SCI is essential to better develop novel therapeutic approaches to restore hemodynamic performance.

Autonomic dysreflexia: a cardiovascular disorder following spinal cord injury

Autonomic dysreflexia （AD） is a serious cardiovascular disorder in patients with spinal cord injury （SCI）. The primary underlying cause of AD is loss of supraspinal control over sympathetic preganglionic neurons （SPNs） caudal to the injury, which renders the SPNs hyper-responsive to stimulation. Central maladaptive plasticity, including C-fiber sprouting and propriospinal fiber proliferation exaggerates noxious afferent transmission to the SPNs, causing them to release massive sympathetic discharges that result in severe hypertensive episodes. In parallel, upregulated peripheral vascular sensitivity following SCI exacerbates the hypertensive response by augmenting gastric and pelvic vasoconstriction. Currently, the majority of clinically employed treatments for AD involve anti-hypertensive medications and Botox injections to the bladder. Although these approaches mitigate the severity of AD, they only yield transient effects and target the effector organs, rather than addressing the primary issue of central sympathetic dysregulation. As such, strategies that aim to restore supraspinal reinnervation of SPNs to improve cardiovascular sympathetic regulation are likely more effective for AD. Recent pre-clinical investigations show that cell transplantation therapy is efficacious in reestablishing spinal sympathetic connections and improving hemodynamic per- formance, which holds promise as a potential therapeutic approach.

Relay strategies combined with axon regeneration: a promising approach to restore spinal cord injury

For decades, numerous investigations have only focused on axon regeneration to restore function after traumatic spinal cord injury （SCI）, as interrupted neuronal pathways have to be reconnected for sensorimotor and autonomic recovery to occur. Experimental approaches have ranged from drug delivery and cell transplantation to genetic manipulations. Certainly, it would be an extraordinary achievement for injured axons to regenerate over long distances, to form synapses with target neurons, and to result in dramatic functional improvement. However, these efforts have been rewarded with limited success to date suggesting that axon regeneration alone may be insufficient to repair compromised functions.

Direct reprogramming of somatic cells into neural stem cells or neurons for neurological disorders

Direct reprogramming of somatic cells into neurons or neural stem cells is one of the most important frontier fields in current neuroscience research. Without undergoing the pluripotency stage, induced neurons or induced neural stem cells are a safer and timelier manner resource in comparison to those derived from induced pluripotent stem cells. In this prospective, we review the recent advances in generation of induced neurons and induced neural stem cells in vitro and in vivo and their potential treatments of neurological disorders.