Dynamics of concentration of neuroinflammatory molecules in ischemic stroke

The aim of the research. To determine the level of transforming growth factor-β (TGF-β), brain-derived neurotrophic factor (BDNF) and nerve growth factor (β-NGF) in the blood serum of patients with ischemic stroke (atherothrombotic subtype) in the acute period and over time.

Materials and methods. The study involved 60 people (50% men and 50% women), who were divided into three groups of 20 people. Group I – healthy individuals; Group II – patients with hypertensive crisis without signs of target organ damage (uncomplicated hypertensive crisis); III – patients with a verified diagnosis of atherothrombotic ischemic stroke that developed against the background of a hypertensive crisis. Patients of groups I, II and III were comparable by gender, age, II and III also by comorbid background. The average age of patients was 56,3 (48,8; 63,3) years.

Results. Based on the results of the study, it was found that in individuals with uncomplicated hypertensive crisis, as well as in patients with ischemic stroke, an increase in the concentration of BDNF and β-NGF in the blood serum was recorded on the first day. TGF-β1 indicators changed only in patients with ischemic stroke. In the group of patients with ischemic stroke, an increase in BDNF, β-NGF, TGF-β1 indicators was observed from the first day from the onset of the disease and persisted throughout the study period. Positive correlations were found between the concentration of BDNF and systolic and diastolic blood pressure (BP), as well as between the concentration of β-NGF and the number of points on the NIHSS scale, SBP and DBP levels.

Conclusion. The registered increase in the concentration of BDNF, β-NGF in patients with hypertensive crisis may indicate the activation of microglia due to damage to the brain as a target organ, even in the absence of neurological symptoms.

1. Gusev E.I., Konovalov A.N., Skvortsova V.I. Neurology. National leadership. Volume 1. Moscow: GEOTAR-Media; 2019. 880p.

2. Xin W.Q., Wei W., Pan Y.L., et al. Modulating poststroke inflammatory mechanisms: Novel aspects of mesenchymal stem cells, extracellular vesicles and microglia. World Journal of Stem Cells. 2021. 13 (8). 1030–1048.

3. Stanley E.R., Biundo F., Gökhan Ş., Differential regulation of microglial states by colony stimulating factors. Frontiers in Cellular Neuroscience. 2023. 17. 1275935.

4. All-Russian Society of Neurologists. Ischemic stroke and transient ischemic attack. Clinical guidelines 2024.

5. Russian Cardiological Society. Arterial hypertension in adults. Clinical guidelines 2024.12.

6. Powers W.J., Rabinstein A.A., Ackerson T., et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/ American Stroke Association. Stroke. 2018; 49 (3). 46–99.

7. Gibon J., Barker P.A. Neurotrophins and proneurotrophins: focus on synaptic activity and plasticity in the brain. The Neuroscientist. 2017. 23 (6). 587–604.

8. Liu D., Flory J., Lin A. Characterization of on-target adverse events caused by TRK inhibitor therapy. Annals of Oncology. 2020. 31 (9). 1207–1215.

9. Tominaga K., Suzuki H.I. TGF-β Signaling in Cellular Senescence and Aging-Related Pathology. International Journal of Molecular Sciences. 2019. 20 (20). 5002.

10. Su C., Miao J., Guo J. The relationship between TGF-β1 and cognitive function in the brain. Brain Research Bulletin. 2023. 205. 110820.

11. Diniz L.P, Matias I., Araujo A.P.B., et al. α-synuclein oligomers enhance astrocyte-induced synapse formation through TGF-β1 signaling in a Parkinson's disease model. Journal of Neurochemistry. 2019. 150 (2). 138–157.

12. Nguyen Q.L., Okuno N., Hamashima T., et al. Vascular PDGFR-alpha protects against BBB dysfunction after stroke in mice. Angiogenesis. 2021. 24 (1). 35–46.

13. Chen J.H., Ke K.F., Lu J.H., et al. Protection of TGF-β1 against neuroinflammation and neurodegeneration in Aβ1-42-induced Alzheimer's disease model rats. PLoS One. 2015. 10 (2). 0116549.

14. Elahi F.M., Wang M.M., Meschia J.F. Cerebral Small Vessel Disease-Related Dementia: More Questions Than Answers. Stroke. 2023. 54 (3). 648–660.

15. Mitra S., Werner C., Dietz D. M. Neuroadaptations and TGF-β signaling: emerging role in models of neuropsychiatric disorders. Molecular Psychiatry. 2022. 27 (1). 296–306.

16. Torrisi S.A., Geraci F., Tropea M.R., et al. Fluoxetine and Vortioxetine Reverse Depressive-Like Phenotype and Memory Deficits Induced by Aβ1-42 Oligomers in Mice: A Key Role of Transforming Growth Factor-β1. Frontiers in Pharmacology. 2019. 10. 693.