Background/Objectives: Despite the decades-old ban on lead in fuel, plumbing, consumer goods, industrial processes, and various materials, it remains a public health threat due to its persistent nature. Zebrafish (Danio rerio) are highly effective for modeling several disorders, including those affecting neurological and behavioral functions, and are well-suited for assessing the impact of environmental toxins like lead. This study aimed to investigate the neurodevelopmental effects of embryonic lead exposure using the zebrafish model system. Methods: Embryos were exposed to lead acetate (PbAc) at concentrations ranging from 0.3 to 0.7 µg/mL using an exposure window of 6 to 48 h post-fertilization (hpf). Results: PbAc exposure produced sublethal teratogenic effects in a subset of larvae across concentrations, including tail and spinal deformities, craniofacial abnormalities, and uninflated swim bladder observed at 7 dpf. At 3 days post-fertilization (dpf), spontaneous circle swimming behavior suspected to be seizure-like was observed in the lead-exposed larvae and was more pronounced under light conditions in a dose-dependent manner. Electrophysiological recordings confirmed that larvae exhibiting circle swimming behavior had heightened neural activity, indicating a potential seizure-like phenotype driven by lead exposure. Conclusions: Our findings suggest that embryonic lead exposure leads to morphological defects and seizure susceptibility, demonstrating lead’s neurotoxic potential during early development. Seizure-like behaviors occurred in a non-linear concentration-dependent manner with a photosensitive component, and elevated baseline neural excitability was confirmed by local field potential (LFP) recordings.

Lymphedema is chronic swelling from lymphatic dysfunction. The vascular delay phenomenon is used in flap reconstruction to increase flap viability through staged selective partial disruption of blood supply to enhance flap survival, followed by flap transfer 7–10 days later. A similar corollary for lymphatics remains unknown. The purpose of this study was to evaluate whether lymphatic preconditioning with staged disruption of lymphatics in the murine hindlimb lymphedema model can be protective against lymphedema. C57BL/6 mice underwent 20 Gy hindlimb irradiation. Group 1 (immediate lymphatic disruption) underwent a circumferential skin incision, complete lymphatic disruption, and popliteal lymph node excision in a single-stage operation. Group 2 (delayed lymphatic disruption) underwent a semi-circumferential inguinal skin incision and dominant lymphatic transection and, 7 days later, received a circumferential skin incision, complete lymphatic transection, and popliteal lymphadenectomy. Paw thickness was measured weekly. Near-infrared laser lymphangiography and immunohistochemistry were performed on D35. Group 2 had a lower average paw thickness (p = 0.0008) and greater lymphatic clearance signal intensity at 24 h (p = 0.0035). Immunohistochemistry indicated an abundance of the lymphatic endothelial-specific marker podoplanin in Group 2 compared to Group 1 (p = 0.03). This study demonstrates evidence for a novel concept of a lymphatic delay phenomenon parallel to the well-known vascular delay phenomenon.