Comparative Evaluation of Imatinib and Nilotinib in a Streptozotocin-Induced Rat Model of Alzheimer’s Disease : Neuroprotective, Anti-inflammatory, and Cognitive Outcomes

Gurkan, Gokhan; Akdag, Burkay; Erdogan, Mumin Alper; Erbas, Oytun

doi:.0..

Journal of Korean Neurosurgical Society > Accepted Articles

Laboratory Research

doi: https://doi.org/10.3340/jkns.2025.0110 [Accepted]

Comparative Evaluation of Imatinib and Nilotinib in a Streptozotocin-Induced Rat Model of Alzheimer’s Disease : Neuroprotective, Anti-inflammatory, and Cognitive Outcomes

Gokhan Gurkan¹

, Burkay Akdag²

, Mumin Alper Erdogan³

, Oytun Erbas⁴

¹Department of Neurosurgery, Izmir Economy University Medical Point Hospital, Izmir, Turkey
²Department of Neurosurgery, Kutahya Health Sciences University, Kutahya, Turkey
³Department of Physiology, Katip Celebi University, Izmir, Turkey
⁴Department of Physiology, Demiroğlu Bilim University, Istanbul, Turkey

Correspondence

Burkay Akdag ,Tel: +90, Fax: +90, Email: burkay.akdag@ksbu.edu.tr

Received: May 21, 2025; Revised: August 28, 2025 Accepted: November 5, 2025. Published online: November 10, 2025.

ABSTRACT

Objective
: Alzheimer’s disease is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) peptide aggregation, representing a major therapeutic target. Emerging evidence suggests certain chemotherapeutic agents may attenuate Aβ pathology.
Methods
: This study investigated the effects of Imatinib, a tyrosine kinase inhibitor with limited blood-brain barrier (BBB) penetration, and Nilotinib, with enhanced BBB permeability, in an intracerebroventricular streptozotocin (ICV-STZ) rat model of Alzheimer’s disease. Outcomes included behavioral assessments (learning latency), hippocampal CA1 and CA3 neuronal counts, and brain concentrations of TNF-α, NF-κB, BDNF, and NRG-1.
Results
: ICV-STZ administration significantly elevated TNF-α and NF-κB levels and reduced BDNF and NRG-1 expression. Both Imatinib and Nilotinib mitigated these alterations, with Imatinib demonstrating greater efficacy despite its limited BBB permeability. Imatinib and Nilotinib reduced TNF-α and NF-κB levels, increased BDNF and NRG-1 expression, and significantly improved cognitive performance, with latency periods extending from 69.8 seconds in the disease model to 193.5 and 183.1 seconds, respectively.
Conclusion
: Imatinib and Nilotinib ameliorated neuroinflammation, restored neurotrophic support, and improved cognitive deficits in a preclinical Alzheimer’s disease model. These findings highlight the therapeutic potential of tyrosine kinase inhibitors, warranting further translational research in human studies.

Key Words: Alzheimer’s disease · Imatinib · Nilotinib · Neurodegeneration · β-amyloid plaque