Katryna Dahlberg

Introduction: Ischemic stroke occurs when lack of blood flow to the brain causes neuronal damage and cell death. Each year there are about 800,000 strokes, and 150,000 related deaths.¹ Stroke is the leading cause of disability in the United States with annual costs of related care around $70 billion dollars.¹ There are a variety of signs of stroke including changes in balance, speech, sensation, or motor function.² The risk factors associated with stroke include hypertension, dyslipidemia, and smoking. The most common diagnostic tool for an ischemic stroke is noncontrast computed tomography (CT). During stroke, neuronal cell death occurs through the apoptotic cascade. At the same time, apoptosis inducing factors enter the nucleus which causes large scale DNA damage and fragmentation.³ Stroke can be treated with tissue plasminogen activator (tPA) if detected within 4.5 hours of symptom onset. However, even after treatment, many individuals will have deficits including motor impairment.^{1, 2} To improve this motor impairment, individuals undergo physical rehabilitation, yet despite the effort and time patients put into rehabilitation their outcomes often do not meet their expectations.  

Research Objectives: The purpose of this study is to identify an alternative stroke rehabilitation technique to increase motor functioning.

Methods: The data source Pubmed was used to search for alternative motor rehabilitation techniques. One option was repetitive transcranial magnetic stimulation (rTMS) which is a non-invasive technique that uses magnetic pulses to stimulate the brain.⁴ When looking into rTMS, articles on changes in motor function, neurogenesis and cell death pathways were identified.  

Results: The main findings of the studies included that high frequency (HF) rTMS significantly decreased the levels of pro-apoptotic proteins and promoted the expression of anti-apoptotic proteins suggesting decreased levels of neuronal cell death when compared to control.^5,6 Neurogenesis was displayed in HF rTMS groups through immunohistochemical staining and western blot analysis.^5,7 HF rTMS also showed significant improvements in motor skills in both mice models and human clinical trials.^{5, 8}

Conclusions: Motor rehabilitation for stroke patients typically involves physical activity. However, a non-invasive therapy called repetitive transcranial magnetic stimulation (rTMS) has shown promise in targeting stroke pathology by affecting neuronal cells at the molecular level. There are still many questions that need to be answered regarding the frequency, duration, and timing of rTMS therapy. Overall, rTMS appears to be a promising alternative for stroke motor recovery.

Works Cited:

1. Feske SK. Ischemic Stroke. Am J Med. 2021;134(12):1457-1464. doi:10.1016/j.amjmed.2021.07.027
2. Mendelson SJ, Prabhakaran S. Diagnosis and Management of Transient Ischemic Attack and Acute Ischemic Stroke: A Review. JAMA. 2021;325(11):1088-1098. doi:10.1001/jama.2020.26867
3. Tuo QZ, Zhang ST, Lei P. Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications. Med Res Rev. 2022;42(1):259-305. doi:10.1002/med.21817
4. Lefaucheur JP, Aleman A, Baeken C, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018) [published correction appears in Clin Neurophysiol. 2020 May;131(5):1168-1169]. Clin Neurophysiol. 2020;131(2):474-528. doi:10.1016/j.clinph.2019.11.002
5. Caglayan AB, Beker MC, Caglayan B, et al. Acute and Post-acute Neuromodulation Induces Stroke Recovery by Promoting Survival Signaling, Neurogenesis, and Pyramidal Tract Plasticity. Front Cell Neurosci. 2019;13:144. Published 2019 Apr 12. doi:10.3389/fncel.2019.00144
6. Baek A, Kim JH, Pyo S, et al. The Differential Effects of Repetitive Magnetic Stimulation in an In Vitro Neuronal Model of Ischemia/Reperfusion Injury. Front Neurol. 2018;9:50. Published 2018 Feb 13. doi:10.3389/fneur.2018.00050 https://pubmed.ncbi.nlm.nih.gov/29487560/
7. Luo J, Zheng H, Zhang L, et al. High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Improves Functional Recovery by Enhancing Neurogenesis and Activating BDNF/TrkB Signaling in Ischemic Rats. Int J Mol Sci. 2017;18(2):455. Published 2017 Feb 20. doi:10.3390/ijms18020455 https://www-mdpi-com.srv-proxy2.library.tamu.edu/1422-0067/18/2/455
8. Du J, Yang F, Hu J, et al. Effects of high- and low-frequency repetitive transcranial magnetic stimulation on motor recovery in early stroke patients: Evidence from a randomized controlled trial with clinical, neurophysiological and functional imaging assessments. Neuroimage Clin. 2019;21:101620. doi:10.1016/j.nicl.2018.101620