Influence of Bone Marrow-Derived Mesenchymal Stem Cell Therapy on Oxidative Stress Intensity in Minimally Conscious State Patients.

Katarzyna Jezierska-Wozniak,Monika Barczewska,Wioleta Czelejewska,Wojciech Maksymowicz,Pawel Wojtacha,Emilia Sinderewicz

doi:10.3390/jcm9030683

Katarzyna Jezierska-Wozniak, Monika Barczewska + Show 4 more

Open Access

https://doi.org/10.3390/jcm9030683

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Abstract

Neurological disorders, including minimally conscious state (MCS), may be associated with the presence of high concentrations of reactive oxygen species within the central nervous system. Regarding the documented role of mesenchymal stem cells (MSCs) in oxidative stress neutralization, the aim of this study is to evaluate the effect of bone marrow-derived MSC (BM-MSC) transplantation on selected markers of oxidative stress in MCS patients. Antioxidant capacity was measured in cerebrospinal fluid (CSF) and plasma collected from nine patients aged between 19 and 45 years, remaining in MCS for 3 to 14 months. Total antioxidant capacity, ascorbic acid and ascorbate concentrations, superoxide dismutase, catalase, and peroxidase activity were analyzed and the presence of tested antioxidants in the CSF and plasma was confirmed. Higher ascorbic acid (AA) content and catalase (CAT) activity were noted in CSF relative to plasma, whereas superoxide dismutase (SOD) activity and total antioxidant capacity were higher in plasma relative to CSF. Total antioxidant capacity measured in CSF was greater after BM-MSC transplantations. The content of ascorbates was lower and CAT activity was higher both in CSF and plasma after the administration of BM-MSC. The above results suggest that MSCs modulate oxidative stress intensity in MCS patients, mainly via ascorbates and CAT activity.

Highlights

Traumatic brain injury (TBI), structural brain lesions, acute endocrine-metabolic disorders, neuronal dysfunctions, and psychogenic unresponsiveness, among many others, provoke consciousness disturbances [1,2,3] which, depending on the severity and duration, may be distinguished in coma and states following coma: minimally conscious state (MCS) and vegetative state (VS) [4]
The current study found that ascorbic acid (AA) concentration in cerebrospinal fluid (CSF) was significantly lower after the first autologous transplantation of BM-mesenchymal stem cells (MSCs) in comparison with the concentration before cell administration, which indicates that AA was intensively consumed in the central nervous system (CNS) tissues in response to a bone marrow-derived MSC (BM-MSC) application, and the level of oxidative stress accompanying MCS may be decreased in response to BM-MSC transplantation
A greater content of AA and CAT activity was detected in CSF in comparison to plasma, suggesting the major role of these factors in maintaining the proper level of reactive oxygen species (ROS) in the CNS of MCS patients

Summary

Introduction

Traumatic brain injury (TBI), structural brain lesions, acute endocrine-metabolic disorders, neuronal dysfunctions, and psychogenic unresponsiveness, among many others, provoke consciousness disturbances [1,2,3] which, depending on the severity and duration, may be distinguished in coma and states following coma: minimally conscious state (MCS) and vegetative state (VS) [4]. Excessive ROS production and losing the scavenging capacity of the antioxidant response system, lead to extensive protein oxidation and lipid peroxidation, which seem to be dangerous in a lipid-rich content nervous system [5,6,7] These changes provoke oxidative damage, cellular degeneration, and functional decline of the central nervous system (CNS) [8,9]. It has been demonstrated that high ROS concentrations reportedly diminish long-term potentiation and synaptic signaling as well as brain plasticity mechanisms [10,11] This condition is considered to be a state of oxidative stress and poses a real threat to the normal functioning of the brain [12,13,14]

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