Future Perspectives in Spinal Cord Repair: Brain as Saviour? TSCI with Concurrent TBI: Pathophysiological Interaction and Impact on MSC Treatment

Abstract

Traumatic spinal cord injury (TSCI), commonly caused by high energy trauma in young active patients, is frequently accompanied by traumatic brain injury (TBI). Although combined trauma results in inferior clinical outcomes and a higher mortality rate, the understanding of the pathophysiological interaction of co-occurring TSCI and TBI remains limited. This review provides a detailed overview of the local and systemic alterations due to TSCI and TBI, which severely affect the autonomic and sensory nervous system, immune response, the blood–brain and spinal cord barrier, local perfusion, endocrine homeostasis, posttraumatic metabolism, and circadian rhythm. Because currently developed mesenchymal stem cell (MSC)-based therapeutic strategies for TSCI provide only mild benefit, this review raises awareness of the impact of TSCI–TBI interaction on TSCI pathophysiology and MSC treatment. Therefore, we propose that unravelling the underlying pathophysiology of TSCI with concomitant TBI will reveal promising pharmacological targets and therapeutic strategies for regenerative therapies, further improving MSC therapy.

Efficacy of extracellular vesicles of different cell origins in traumatic brain injury: A systematic review and network meta-analysis

“…Stem cell therapies have also been used in clinical trials ( Shahror et al, 2020 ). The efficacy of MSC in neurodegenerative diseases has also been widely reported ( Peruzzaro et al, 2019 ; Köhli et al, 2021 ). However, although MSC has also been found to improve neurological function after TBI, inhibit the expression of apoptosis-related proteins Bax and Caspase−3, and also inhibit the secretion of pro-inflammatory and anti-inflammatory factors ( Zhang et al, 2013 ; Shahror et al, 2019 ).…”