Biomarkers of Angiogenesis and Neuroplasticity as Promising Clinical Tools for Stroke Recovery Evaluation

One question is all you need. 'Are you 100% recovered?' Biomarkers are useless, they do nothing for recovery. If they are needed for therapy payment figure out something more appropriate. 

Biomarkers of Angiogenesis and Neuroplasticity as PromisingClinical Tools for Stroke Recovery Evaluation

Lidia Wlodarczyk 1 , Rafal Szelenberger 2 , Natalia Cichon 3,* , Joanna Saluk-Bijak 2 , Michal Bijak 3 and Elzbieta Miller 4


 Citation: Wlodarczyk, L.; Szelenberger, R.; Cichon, N.; Saluk-Bijak, J.; Bijak, M.; Miller, E. Biomarkers of Angiogenesis and Neuroplasticity as Promising Clinical Tools for Stroke Recovery Evaluation. Int. J. Mol. Sci. 2021, 22, 3949. https://doi.org/10.3390/ijms22083949 Academic Editor: Valentina Arnao Received: 2 March 2021 Accepted: 8 April 2021 Published: 11 April 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 

1 Department of Occupational Diseases and Environmental Health, Nofer Institute of Occupational Medicine, 91-348 Lodz, Poland; lidia.monika.wlodarczyk@gmail.com 

2 Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland; rafal.szelenberger@edu.uni.lodz.pl (R.S.); joanna.saluk@biol.uni.lodz.pl (J.S.-B.) 

3 Biohazard Prevention Centre, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland; michal.bijak@biol.uni.lodz.pl 

4 Department of Neurological Rehabilitation, Medical University of Lodz, Milionowa 14, 93-113 Lodz, Poland; elzbieta.dorota.miller@umed.lodz.pl * Correspondence: natalia.cichon@biol.uni.lodz.pl 

 

Abstract:

 Several key issues impact the clinical practice of stroke rehabilitation including a patient’s medical history, stroke experience, the potential for recovery, and the selection of the most effective type of therapy. Until clinicians have answers to these concerns, the treatment and rehabilitation are rather intuitive, with standard procedures carried out based on subjective estimations using clinical scales. Therefore, there is a need to find biomarkers that could predict brain recovery potential in stroke patients. This review aims to present the current state-of-the-art stroke recovery biomarkers that could be used in clinical practice. The revision of biochemical biomarkers has been developed based on stroke recovery processes: angiogenesis and neuroplasticity. This paper provides an overview of the biomarkers that are considered to be ready-to-use in clinical practice and others, considered as future tools. Furthermore, this review shows the utility of biomarkers in the development of the concept of personalized medicine. Enhancing brain neuroplasticity and rehabilitation facilitation are crucial concerns not only after stroke, but in all central nervous system diseases. Keywords: stroke; recovery; biomarkers; prognosis; personalized medicine; rehabilitation 1. Introduction According to the updated definition, stroke is an acute episode of neurological dysfunction caused by the cerebral, spinal cord, retinal infarction, or hemorrhage (including subarachnoid hemorrhage). The medical state may persist longer than 24 h or of any duration, if focal infarction or hemorrhage relevant to the symptoms has been shown by imaging (like CT or MRI scans) or autopsy [1]. As a medical condition, stroke is a complex, heterogeneous disease in terms of semiology, etiology, and possible treatment strategies. The clinical symptoms are directly related to the topography of brain tissue damage and commonly include paresis (most frequently diagnosed), numbness, speech disorder (i.e., aphasia, dysarthria), vision impairment, and disturbed coordination [2]. There are two main causes of stroke associated with its etiology: ischemia and hemorrhage. Ischemic stroke may develop from various origins, including embolism (arterial or cardiac in origin), decreased perfusion (arterial occlusion or stenosis), and thrombosis (as a primary or secondary abnormality of hemostasis). Focal ischemia leads to irreversible injury in a core region and partially reversible damage in the surrounding penumbra zone. In contrast, hemorrhagic stroke is associated with the leakage or rupture of the artery and remains in a minority—approximately only 15% of strokes are diagnosed as hemorrhages. Despite the separation of the stroke into two main causes, the proportions of pathological and etiological subtypes differ depending on age, race, ethnic origin, and nationality. Although the mortality rate from a stroke has decreased over the recent years, it remains the main cause of disability within professionally active people over 40 years of age [3]. There are quite effective early treatment strategies for ischemic strokes, like intravenous tissue plasminogen activator (tPA) or endovascular thrombectomy (EVT) [4]. Patients are eligible for medical thrombolysis (intravenous administration of tissue plasminogen activator) within 4.5 h of known symptom onset (in various situations, the thrombolysis time window may extend beyond 4.5 h). The time window for EVT treatment is available for all patients who arrived at the hospital within 6 h and, in particular cases, within 6–24 h (including stroke upon awakening with unknown onset time). All acute stroke patients, who are not receiving tPA or EVT therapy, should be administrated with acetylsalicylic acid (ASA) [5]. Furthermore, antiplatelet drugs should be continued as secondary ischemic stroke prevention. Treatment of hemorrhage stroke focuses on reducing intracranial and blood pressure, preventing seizures and vessel spasm. Moreover, surgical hematoma drainage should be considered if necessary [4,6]. In every case, the initial treatment is aimed at improving basic vital functions by the connection of a drip and oxygen. During acute inpatient care, stroke patients should also undergo investigations to determine stroke mechanisms, guide stroke prevention, and future management decisions. To provide medical care, an interdisciplinary medical team on the stroke unit should be set up, thus providing a suitable evaluation of the patient’s health condition and enabling the selection of an appropriate type of post-stroke rehabilitation, which should be implemented immediately after the patient’s condition stabilization. Rehabilitation therapy should begin as soon as the patient can participate in physical exercises. The rehabilitation process should be directed at affected functioning domains including motor impairments, speech disorders, cognitive dysfunction, vision disturbances, etc. Post-stroke rehabilitation uses selected therapies for motor function improvement like aerobic training (AE), repetitive task training (RTT), constraint-induced movement therapy (CIMT), mirror therapy, muscle strengthening, electromechanical, robot-assisted training, noninvasive brain stimulation (NIBS), and neuromuscular electrical stimulation (NMES) [7]. To maximize the post-stroke care effectiveness, coordinated effort from the medical team is required including physical and occupational therapists, speech-language pathologists, psychologists, nutritionists, recreation therapists, and others [8]. The main goal of this review is to introduce a new approach for stroke recovery biomarkers, which are based on angiogenesis and neuroplasticity processes. The proteins present in the manuscript could be used to determine the innovative algorithm of the procedure to evaluate an outcome of post-stroke patients and applied therapy. 

 

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