Can rehabilitation exercise alter the oxidative profile in stroke patients?

Oxidative stress can trigger the deterioration of the cerebral extracellular endothelial matrix and may lead to a stroke event. There is evidence that rehabilitation exercise alters the oxidative profile. This systematic review intends to observe in the literature if rehabilitation exercise can contribute to modifying the oxidative profile in the stroke. For it, we investigated works from 2012 until August 2017, in the PubMed, Lilacs and PEDro databases. Initially, 30 documents were selected, but only one article met the inclusion criteria. These results showed that new studies must be carried out to affirm that the therapeutic exercises could improve the oxidative profile in stroke patients. Correspondence to: Tatmatsu-Rocha JC, Medicine School, Physiotherapy Department, Federal University of Ceara, Fortaleza, Ceara, Brazil, Tel: +55(85) 33668632; Email: tatmatsu@gmail.com Received: October 20, 2017; Accepted: November 30, 2017; Published: December 04, 2017 Introduction Stroke is the most common type since 85% to 90% of people were diagnosed with ischemic stroke [1]. Pathophysiology of stroke, there is a change in the encephalic circulation, leading to limitations in the performance of body structure and function [2]. Ischemic stroke remains to be one of the most severe neurological diseases, which results in permanent deterioration in motor and cognitive abilities [3]. Plastic reorganization occurs immediately after stroke. Following focal damage to the motor cortex and its descending pathways, the surviving portions of the brain usually undergo substantial structural and functional reorganization [4]. Because of the difficulties in measuring the stress biomarkers in stroke rehabilitation research is crucial to better understand the pathophysiology. However, because of the difficulties in measuring unstable free radicals in human samples, the degree of oxidative stress can be determined by measuring the stable end-products of oxidatively modified proteins, lipids, and DNA [5].Some studies have shown alterations in the levels of oxidative stress in stroke patients, such as that of Ning et al [6], in which it was suggested that oxidative stress could trigger the deterioration and active remodelling of the extracellular endothelial matrix. Other authors also indicate that oxidative stress would play a critical role in the cerebrovascular dysfunction induced by angiotensin-converting enzyme type 2 (ACE2) deficiency by converting angiotensin II to angiotensin and thus protecting against the effects of angiotensin, which could explain some differences among users regarding post-stroke symptoms. These events could occurs due to high production of reactive oxygen species and reactive nitrogen species associated with the lack of antioxidants [7]. This imbalance generates lipid peroxidation, protein denaturation, DNA breakdown, and causes cellular damage, which can lead to autophagy, necrosis, or cellular apoptosis [8]. Because of these repercussions, the number of studies seeking to identify means to control the effects of oxidative stress is increasing. According to Austin et al. (2014), researchers with animals in ischemic conditions suggest that a high load of exercises is capable of stimulating genes and proteins that protect the brain from damage from oxidative stress without increasing the number of free radicals, besides regulating reactive substances that act as markers of this phenomenon. Moreover, physical activity influence the cellular oxidative profile, and therefore, interventions with exercise could promote an antioxidative effect and thus prevent the worsening of the condition [9,10]. Functional plasticity is a mechanism in which the neural networks that remain after an ischemic brain injury undergo structural and synaptic changes to restore loss of function [11]. In this context, it is suggested that the rehabilitation of the AVE occurs as early as possible, due to the phenomenon of neuronal plasticity, through which recovery of part of the lost movements occurs. Early intervention could return motor capacity as well as allow the user to carry out their daily life activities alone [12]. The present study aims to identify if there is evidence that the therapeutic exercises are capable of acting on the effects of oxidative stress from the stroke. Methods A rapid systematic review of the literature was conducted in search of original articles on therapeutic exercises on the effects of oxidative stress in the Stroke on the PubMed, Lilacs and PEDro databases. The search period was January 2012 until August 2017. The search syntaxes for the database Pubmed are (Oxidative Stresses) OR Stresses, Oxidative) OR Stress, Oxidative) AND (Strokes) OR Cerebrovascular Braga AS (2017) Can rehabilitation exercise alter the oxidative profile in stroke patients? Volume 2(5): 2-4 Rheumatol Orthop Med, 2017 doi: 10.15761/ROM.1000135 Original articles were included whose central theme related to therapeutic exercise in post-stroke, and the primary outcome was an evaluation of biomarkers of oxidative stress. Studies where the primary focus was not oxidative stress or studies in animals. Results and discussion A total of 30 articles identified in the databases of which one included in the synthesis, a process detailed in Figure 1. In this work, 30 studies with the keywords defined were initially listed. However, 25 studies were excluded because the majority did not present oxidative stress analysis in their methodology or did not present studies related to rehabilitation exercise [13-37]. Five articles [1,38-41] were included in their summaries the keywords. However, during the reading of the full text, only the paper of Ciancarelli et al [40] met the inclusion criteria of our research. About Ciancarelli work, patients selected to participate in this study were enrolled at the Nova Salus Rehabilitation Center from October 2011 to January 2012. The participants inclusion criteria was: Participants within the first thirty days after the first moderate or severe ischemic stroke event; presenting hemiparesis who could control the trunk in the seated posture for at least ten seconds, be able to walk and not being sedentary. During the study, the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), the Barthel Index and the Katz Index were used as measuring tools. The protocol used in the research had as primary objective to recover neurological deficits and Records identified in the search database. n = 31 Records after deleting the duplicates. n = 30 Selected records after reading summaries. n = 5 Excluded Records No = 33 Full-text records evaluated by eligibility. n = 1 Records included in the synthesis n = 1 Deleted full-text records n = 3 Excluded r cords based on the inclusion criteria n = 25 Figure 1. Flowchart for study selection. Accident) OR Cerebrovascular Accidents) OR CVA (Cerebrovascular Accident) OR CVAs (Cerebrovascular Accident) OR Cerebrovascular Apoplexy) OR Apoplexy, Cerebrovascular) OR Vascular Accident, Brain) OR Brain Vascular Accident) OR Brain Vascular Accidents) OR Vascular Accidents, Brain) OR Cerebrovascular Stroke) OR Cerebrovascular Strokes) OR Stroke, Cerebrovascular) OR Strokes, Cerebrovascular) OR Apoplexy) OR Cerebral Stroke) OR Cerebral Strokes) OR Cerebral Strokes) OR Stroke, Cerebral) OR Strokes, Cerebral) OR Stroke, Acute) OR Acute Stroke) OR Acute Strokes) OR Strokes, Acute) OR Cerebrovascular Accident, Acute) OR Acute Cerebrovascular Accident) OR Acute Cerebrovascular Accidents) OR Cerebrovascular Accidents, Acute) AND (Therapy, Exercise) OR Exercise Therapies) OR Therapies, Exercise) OR Rehabilitation Exercise) OR Exercise, Rehabilitation) OR Exercises, Rehabilitation) OR Rehabilitation Exercises) OR Remedial Exercise) OR Exercise, Remedial) OR Exercises, Remedial) OR Remedial Exercises) OR (Modalities, Physical Therapy) OR Modality, Physical Therapy) OR Physical Therapy Modality) OR Physical Therapy Techniques) OR Physical Therapy Technique) OR Techniques, Physical Therapy) OR Physiotherapy (Techniques) OR Physiotherapies (Techniques)) OR Neurological Physiotherapy) OR Physiotherapy, Neurological) OR Neurophysiotherapy). The search syntaxes for the database Lilacs and PEDro was oxidative stress AND stroke. We searched for articles in the English and Portuguese languages, published in the last five years. This study was evaluated by two independent reviewers and was included in a second entry database, Excel, and then reviewed by both. Any disagreements were resolved by discussion between reviewers to reach consensus or by a third reviewer. Braga AS (2017) Can rehabilitation exercise alter the oxidative profile in stroke patients? Volume 2(5): 3-4 Rheumatol Orthop Med, 2017 doi: 10.15761/ROM.1000135 to recover functional abilities during the activities of daily life and to improve the self-care. The proposed treatment was performed for six weeks, for six days, with two sessions of 45 minutes per day. Blood analysis of stroke patients was performed before and aftercare. No significant differences were found in blood pressure, MBI and HDL-C values between the two groups before and after rehabilitation. The amounts of cholesterol, triglycerides and LDL-C were higher in stroke patients than in the control group, values that did not change significantly at the end of treatment. Significant results of our review it is that the antioxidant capacity of plasma was lower in those who had the stroke before and after therapeutic intervention. Besides, values of peroxidative by-products and Nitric Oxide metabolites have been shown to be high in stroke patients compared to healthy subjects. These costs decreased significantly in stroke patients although they remained at higher levels than the control group and reinforced that rehabilitation exercise could alter the oxidative profile. Limitation: Possible limitations of this review are the date of publication and a limited


Introduction
Stroke is the most common type since 85% to 90% of people were diagnosed with ischemic stroke [1]. Pathophysiology of stroke, there is a change in the encephalic circulation, leading to limitations in the performance of body structure and function [2]. Ischemic stroke remains to be one of the most severe neurological diseases, which results in permanent deterioration in motor and cognitive abilities [3]. Plastic reorganization occurs immediately after stroke. Following focal damage to the motor cortex and its descending pathways, the surviving portions of the brain usually undergo substantial structural and functional reorganization [4]. Because of the difficulties in measuring the stress biomarkers in stroke rehabilitation research is crucial to better understand the pathophysiology.
However, because of the difficulties in measuring unstable free radicals in human samples, the degree of oxidative stress can be determined by measuring the stable end-products of oxidatively modified proteins, lipids, and DNA [5].Some studies have shown alterations in the levels of oxidative stress in stroke patients, such as that of Ning et al [6], in which it was suggested that oxidative stress could trigger the deterioration and active remodelling of the extracellular endothelial matrix. Other authors also indicate that oxidative stress would play a critical role in the cerebrovascular dysfunction induced by angiotensin-converting enzyme type 2 (ACE2) deficiency by converting angiotensin II to angiotensin and thus protecting against the effects of angiotensin, which could explain some differences among users regarding post-stroke symptoms. These events could occurs due to high production of reactive oxygen species and reactive nitrogen species associated with the lack of antioxidants [7]. This imbalance generates lipid peroxidation, protein denaturation, DNA breakdown, and causes cellular damage, which can lead to autophagy, necrosis, or cellular apoptosis [8].
Because of these repercussions, the number of studies seeking to identify means to control the effects of oxidative stress is increasing.
According to Austin et al. (2014), researchers with animals in ischemic conditions suggest that a high load of exercises is capable of stimulating genes and proteins that protect the brain from damage from oxidative stress without increasing the number of free radicals, besides regulating reactive substances that act as markers of this phenomenon. Moreover, physical activity influence the cellular oxidative profile, and therefore, interventions with exercise could promote an antioxidative effect and thus prevent the worsening of the condition [9,10]. Functional plasticity is a mechanism in which the neural networks that remain after an ischemic brain injury undergo structural and synaptic changes to restore loss of function [11]. In this context, it is suggested that the rehabilitation of the AVE occurs as early as possible, due to the phenomenon of neuronal plasticity, through which recovery of part of the lost movements occurs. Early intervention could return motor capacity as well as allow the user to carry out their daily life activities alone [12].
The present study aims to identify if there is evidence that the therapeutic exercises are capable of acting on the effects of oxidative stress from the stroke. Original articles were included whose central theme related to therapeutic exercise in post-stroke, and the primary outcome was an evaluation of biomarkers of oxidative stress. Studies where the primary focus was not oxidative stress or studies in animals.

Results and discussion
A total of 30 articles identified in the databases of which one included in the synthesis, a process detailed in Figure 1.
In this work, 30 studies with the keywords defined were initially listed. However, 25 studies were excluded because the majority did not present oxidative stress analysis in their methodology or did not present studies related to rehabilitation exercise . Five articles [1,[38][39][40][41] were included in their summaries the keywords. However, during the reading of the full text, only the paper of Ciancarelli et al [40] met the inclusion criteria of our research. About Ciancarelli work, patients selected to participate in this study were enrolled at the Nova Salus Rehabilitation Center from October 2011 to January 2012. The participants inclusion criteria was: Participants within the first thirty days after the first moderate or severe ischemic stroke event; presenting hemiparesis who could control the trunk in the seated posture for at least ten seconds, be able to walk and not being sedentary.
During the study, the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), the Barthel Index and the Katz Index were used as measuring tools. The protocol used in the research had as primary objective to recover neurological deficits and Records identified in the search database. n = 31 Records after deleting the duplicates. n = 30 Selected records after reading summaries. n = 5

Excluded Records Nº = 33
Full-text records evaluated by eligibility. n = 1 Records included in the synthesis n = 1 Deleted full-text records n = 3 Excluded records based on the inclusion criteria n = 25  to recover functional abilities during the activities of daily life and to improve the self-care. The proposed treatment was performed for six weeks, for six days, with two sessions of 45 minutes per day.
Blood analysis of stroke patients was performed before and aftercare. No significant differences were found in blood pressure, MBI and HDL-C values between the two groups before and after rehabilitation. The amounts of cholesterol, triglycerides and LDL-C were higher in stroke patients than in the control group, values that did not change significantly at the end of treatment. Significant results of our review it is that the antioxidant capacity of plasma was lower in those who had the stroke before and after therapeutic intervention. Besides, values of peroxidative by-products and Nitric Oxide metabolites have been shown to be high in stroke patients compared to healthy subjects. These costs decreased significantly in stroke patients although they remained at higher levels than the control group and reinforced that rehabilitation exercise could alter the oxidative profile. Limitation: Possible limitations of this review are the date of publication and a limited number of databases included in the search.

Conclusion
Systematic reviews have the objective of bringing state of the art on a whole subject of scientific relevance. This report has provided an updated and considerably expanded picture of the role of rehabilitation exercises in the oxidative profile of people who had the stroke and providing an opportunity for advancing research in this area. In this study, it is concluded that although there is evidence that exercise rehabilitation changes the oxidative profile, there are few studies to ensure that exercise rehabilitation improves oxidative stress in stroke patients. Therefore, caution would be encouraged in interpreting these findings because of the small number of research included in this review.