👤 Yigit Uyanikgil

Nerve Guidance Conduits (NGCs) are crucial for reducing trauma during nerve repair, directing axonal growth, and preventing scar tissue formation. In this study, tubular functional NGCs were developed based on vertically aligned electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers (vNGC). They were functionalized by conjugating them with bioactive mimetic peptides: a laminin-derived peptide (LD-BP) to promote vascularization, and nerve growth factor (NGF-BP) and brain-derived neurotrophic factor (BDNF-BP) mimetic peptides to support neural differentiation. The vascular differentiation of HUVECs in response to LD-BP, and the neuronal differentiation of PC12 cells in response to NGF-BP and BDNF-BP, were assessed. The results demonstrated that this approach enabled the fabrication of tubular vNGCs with various diameters, and that vertically aligned PLGA nanofibers significantly improved their structural integrity. Furthermore, BP-conjugated vNGCs outperformed non-conjugated control groups in promoting both vascular and neural differentiation. Importantly, peptide conjugation did not induce cytotoxicity or significantly alter the biodegradability of the vNGCs, supporting their suitability for biomedical applications. Finally, bifunctional vNGCs (BiF-vNGCs), conjugated with LD-BP, NGF-BP, and BDNF-BP, were tested in a rat model of sciatic nerve injury. The BiF-vNGCs showed superior performance compared to unmodified vNGC, Control and s-Control groups, effectively promoting vascularization and neural regeneration in vivo, offering a viable alternative to conventional nerve regeneration methods. Show less

Radiation-induced brain injury causes significant neurotoxicity and cognitive dysfunction in patients undergoing radiotherapy for brain tumors. This study aimed to evaluate the neuroprotective effects of intranasal ketamine on radiation-induced brain injury, specifically focusing on its modulation of perineuronal networks (PNNs), extracellular matrix components, and neuroinflammation. Eighteen male New Zealand White Rabbits were divided into three groups: normal controls, irradiation (IR) with saline (IR + saline), and IR with ketamine (IR + ketamine). Whole-brain IR (20 Gy) was applied to the IR groups, and ketamine (2 mg/kg/day) was administered intranasally for 15 days. Biochemical markers, including malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), brain-derived neurotrophic factor (BDNF), ADAMTS4, and syndecan-1 levels, were measured. Histopathological analysis of hippocampal and cerebellar regions assessed neuronal survival and astrogliosis. Magnetic resonance spectroscopy (MRS) evaluated lactate and Ketamine administration significantly reduced oxidative stress (MDA) and inflammatory markers (TNF-α) while restoring BDNF levels compared to the IR + saline group. ADAMTS4 and syndecan-1 levels were reduced, changes consistent with PNN-associated extracellular matrix dynamics, but without direct confirmation by core PNN markers such as aggrecan or WFA staining. Histopathology showed increased neuronal survival and decreased reactive astrogliosis in ketamine-treated groups. Intranasal ketamine demonstrates significant neuroprotective effects in a radiation-induced brain injury model by reducing oxidative stress and inflammation, modulating extracellular matrix components, and preserving neuronal integrity. These findings highlight ketamine's potential as a therapeutic agent, although direct PNN markers and broader cytokine panels were not assessed. Overall, ketamine showed neuroprotective effects across biochemical, histological, and MRS-supported metabolic readouts. Show less