Role of vascular endothelial growth factor for the microvascular blood supply during axonal regrowth (elongation, collateral branching and terminal sprouting) for recovery of function after experimental facial nerve branch injury

• Applicant: Professor Dr. Orlando Guntinas-Lichius
• Subject Area: Otolaryngology, Phoniatrics and Audiology ; Experimental and Theoretical Network Neuroscience
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 577206028

This research project VEGF-NERVE-REGENERATION investigates how vascular endothelial growth factor (VEGF) influences facial nerve regeneration after injury. Facial palsy, caused by facial nerve damage, often leads to permanent dysfunction with synkinesis (involuntary muscle co-contraction), impaired blinking, eating, and emotional expression, severely affecting quality of life. Recovery is usually poor because regenerating axons misdirect, causing improper reconnection at three levels: failed fascicular pathfinding, excessive collateral branching, and terminal sprouting with polyinnervation of muscle junctions. These maladaptive processes result in uncoordinated movements and persistent deficits. VEGF-NERVE-REGENERATION focuses on whether stimulating early revascularization at the injury site can improve nerve regeneration. Blood vessels are crucial for guiding Schwann cells and axons during repair. VEGF, a potent angiogenic factor, promotes new vessel formation, Schwann cell invasion, remyelination, and axonal growth. However, it remains unclear whether abundant or sparse revascularization yields better outcomes, as excessive vascularization may trigger harmful inflammation. In this study, we will use a rat model (buccal-buccal anastomosis of the facial nerve, i.e. transection and suture of the buccalis branch of the facial nerve) to analyze how VEGF affects early vascularization, axonal branching, and muscle reinnervation quality. One hundred female Wistar rats will be divided into ten groups, receiving different treatments: no surgery, nerve repair only, VEGF injections, placebo, or anti-VEGF antibody. VEGF or its neutralizing antibody will be injected daily at the suture site for 56 days. Functional recovery will be measured by video-based motion analysis of whisker movements (protraction, retraction, frequency, amplitude, and velocity) over eight weeks. Morphological studies will assess capillary density, collateral axonal branching via retrograde labeling, and neuromuscular junction polyinnervation using immunohistochemistry and DAB staining to visualize functioning capillaries. The main hypothesis is that early, well-guided revascularization—not merely the number of blood vessels—determines better recovery by reducing pathological branching and improving targeted muscle innervation. The project spans 24 months and builds on more than 20 years of prior work by the research team. It leverages existing expertise in facial nerve research and the infrastructure of the Facial-Nerve-Center at Jena University Hospital. If successful, this approach may lead to novel therapies to enhance motor recovery after facial nerve injuries, with potential translation into clinical trials (e.g., phase I JECTU study). The study adheres to ethical standards, animal welfare guidelines, and FAIR data principles, aiming for open access publication of results and contributing to sustainable research practices.

• DFG Programme: Research Grants