G. F. P. Kusuma¹* (https://orcid.org/0000-0001-6646-8501)
T. G. B. Mahadewa¹ (https://orcid.org/0000-0002-4445-4085)
N. N. S. Budayanti² (https://orcid.org/0000-0002-6841-415X)
T. Apriawan³ (https://orcid.org/0000-0003-4063-0982)
A. B. S. Satyarsa⁴ (https://orcid.org/0000-0002-2153-2271)

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: 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 7^th or 14^th 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 7^th and 14^th day. Cognitive performance improved markedly in the AD-MSCs group, with shorter­ escape times in the Barnes maze on both 7^th and 14^th day. 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: apoptosis, brain-derived neurotrophic factor, cognitive function, rat model mesenchymal stem cells, traumatic brain injury