Immunohistochemical neuroinflammatory markers in the hippocampus of PTZ-kindled rats under conditions of rapamycin and axitinib treatment




experimental epileptic syndrome, kindling, pentylenetetrazol, rapamycin, axitinib, HIF-1α, TNF-α, NF-kB, mTOR, tyrosine kinase B


The aim of the study is to determine the level of HIF-1α, TNF-α, and NF-kB in the hippocampus of kindled rats treated with rapamycin and axitinib.

Materials and methods. Kindling was produced in 29 rats by administration of three-week pentylenetetrazole (PTZ, 35.0 mg/kg, i.p.). Treatment with rapamycin (0.5 mg/kg, i.p.) and axitinib (2.5 mg/kg, i.p.) was performed for ten days in fully kindled rats. The avidin-biotin-peroxidase method was used for hippocampal slice staining. For negative control, staining was performed using only secondary antibodies.

Results. The HIF-1α expression increased in kindled rats raised by 1.77 times compared to the control (p<0.001). Axitinib treatment resulted in of HIF-1α level of 16.7 % (p<0.05) compared with kindled animals, while combined treatment with rapamycin and axitinib reduced HIF-1α by 33.8 % (p<0.01). In kindled rats, TNF-α expression was 3.74 times greater than in control (p<0.001). Rapamycin treatment reduced TNF-α by 31.0 % (p<0.01). Axitinib treatment caused a reduction of TNF-α by 21.1 % (p<0.05). Combined treatment with rapamycin and axitinib reduced TNF-α by 48.0 % (p<0.001) but still exceeded the TNF-α in control by 1.95 times (p<0.01). NF-kB level in kindled rats exceeded the control by three times (p<0.001). Rapamycin caused a reduction of 19.3 % (p>0.05), while axitinib – by 26.5 % (p<0.05) compared with kindled rats. Combined treatment with rapamycin and axitinib resulted in NF-kB reduction by 56.7 % compared with kindled rats (p<0.001). 

Conclusions. PTZ-kindling resulted in an increase in the immunoreactivity of HIF-1α, TNF-α, and NF-kB in the hippocampus. Combined treatment with rapamycin and axitinib engendered prevention of generalized seizures and normalized the level of HIF-1α and NF-kB with a significant reduction of TNF-α. Effects of treatment favours of synergy action of rapamycin and axitinib

Author Biographies

Olesya Poshyvak, Danylo Halytsky Lviv National Medical University

PhD, Associate Professor

Department of Pharmacology

Oleh Pinyazhko, Danylo Halytsky Lviv National Medical University; University of Information Technology and Management in Rzeszów

Doctor of Medical Sciences, Professor

Department of Pharmacology

Department of Civilization Diseases and Regenerative Medicine

Leonid Godlevsky, Odesa National Medical University

Doctor of Medical Sciences, Professor

Department of Biophysics, Informatics and Medical Devices

Mykhailo Pervak, Odesa National Medical University

PhD, Associate Professor

Department of Simulation Medical Technologies

Olha Yehorenko, Odesa National Medical University


Department of Simulation Medical Technologies

Zuleyha Doganyigit, Yozgat Bozok University

PhD, Professor (Associate)

Department of Histology and Embryology

Asli Okan, Yozgat Bozok University

(PhD) Professor (Assistant)

Department of Histology and Embryology

Enes Akyuz, University of Health Sciences

PhD, Professor (Associate)

Department of Biophysics

Suliman N. A. Hathal, Danylo Halytsky Lviv National Medical University

Postgraduate student

Department of Pharmacology

Artem Liashenko, Odesa National Medical University

PhD, Asociate Professor

Department of Biophysics, Informatics and Medical Devices


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How to Cite

Poshyvak, O., Pinyazhko, O., Godlevsky, L., Pervak, M., Yehorenko, O., Doganyigit, Z., Okan, A., Akyuz, E., Hathal, S. N. A., & Liashenko, A. (2023). Immunohistochemical neuroinflammatory markers in the hippocampus of PTZ-kindled rats under conditions of rapamycin and axitinib treatment. ScienceRise: Pharmaceutical Science, (1(41), 23–31.



Pharmaceutical Science