Ukr.Biochem.J. 2026; Volume 98, Issue 3, May-Jun, pp. 54-64

doi: https://doi.org/10.15407/ubj98.03.054

Adipocyte-derived mesenchymal stem cells injection attenuates neuronal apoptosis and enhances cognitive recovery after moderate traumatic brain injury in rats

09.06.2026   Uncategorized

G. F. P. Kusuma1*, T. G. B. Mahadewa1, N. N. S. Budayanti2,
T. Apriawan3, A. B. S. Satyarsa4

1Neurosurgery Division, Department of Surgery, Faculty of Medicine
Universitas Udayana, Denpasar, Bali, Indonesia;
2Department of Microbiology, Faculty of Medicine Universitas Udayana,
Denpasar, Bali, Indonesia;
3Department of Neurosurgery, Airlangga University Teaching Hospital,
Surabaya, East Java, Indonesia;
4Neurosurgical Residency Program, Faculty of Medicine
Universitas Udayana, Denpasar, Bali, Indonesia;
*e-mail: febby_pratama@unud.ac.id

Received: 25 January 2026; Revised: 30 March 2026;
Accepted: 29 May 2026; Available on-line: 18 June 2026

Background. Traumatic brain injury (TBI) remains one of the leading causes of long-term disabili­ty worldwide. The secondary brain injury phase, which develops hours to days after primary trauma, is a critical therapeutic window for therapeutic interventions, however, no available therapy has been proven effective. Objective. To estimate the effect of adipose-derived mesenchymal stem cells (AD-MSCs) therapy on neuronal apoptosis, brain-derived neurotrophic factor (BDNF) level, and cognitive function in a rat model of moderate TBI. Methods. AD-MSCs from rat adipose tissue were isolated and analyzed using standardized techniques. Adult male Wistar rats were anesthetized, a left-sided craniectomy was performed and a modera­te traumatic brain injury was induced by releasing a metal cylinder through a guiding tube. Following the impact, the incision was closed using absorbable sutures. At 24 hours following TBI, eight microinjections each consisting of 2·105 AD-MSCs in 5 µl PBS were administered in the pericontusional cortex. Control animals received equivalent volumes of sterile saline. Animals were euthanized on 7th or 14th day and the brain was collected for analysis. At the time point prior to euthanasia, rats underwent cognitive testing. Apop­totic index was evalua­ted by TUNEL assay, BDNF level by ELISA, cognitive performance by Barnes maze test. Results. Macroscopic­ brain examination revealed enhanced cortical regeneration and vascularization in AD-MSCs treated rats compared with controls. The apoptotic index was significantly lower in the AD-MSCs group on both 7th and 14th days. Cognitive performance improved markedly in the AD-MSCs group, with shorter­ escape times in the Barnes maze on both 7th and 14th days. In contrast, BDNF levels did not differ between groups at either time point. Conclusion. These findings demonstrate both neuroprotective and neuroregenerative effects of AD-MSCs and highlight its administration as a promising therapeutic strategy for mitigating secondary­ brain injury after TBI.

Keywords: , , , ,

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