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Intracerebral hemorrhage is a lethal cerebrovascular disease, and the inevitable secondary brain injury (SBI) is responsible for serious disability and death. Perfect therapeutic goal is to minimize SBI and restore neurobehavioral functions. Recently, neuroprotection is highlighted to reduce SBI, but it still faces "Neuronal survival but impaired functions" dilemma. Herein, this work further proposes a novel combinational therapeutic strategy of neuroprotection and neurogenesis toward this goal. However, appropriate therapeutic agents are rarely reported, and their discovery and development are urgently needed. Selenium participates in various physiological/pathological processes, which is hypothesized as a potential targeting molecule. To explore this effect, this work formulates an ultra-small selenium nanodot with a seleno-amino acid derived carbon dot domain and a hydrophilic PEG layer, surprisingly finding that it increases various selenoproteins levels at perihematomal region, to not only exert multiple neuroprotective roles at acute phase but promote neurogenesis and inhibit glial scar formation at recovery phase. At a safe dose, this combinational strategy effectively prevents SBI and recovers neurobehavioral functions to a normal level. Furthermore, its molecular mechanisms are revealed to broaden application scopes in other complex diseases., (© 2024. The Author(s).)

Background Animal models are essential in simulating clinical diseases and facilitating relevant studies. New method We established a precise canine model of traumatic brain injury (TBI) based on cerebral motor cortex injury which was confirmed by neuroimaging, electrophysiology, and a series of motor function assessment methods. Twelve beagles were divided into control, sham, and model groups. The cerebral motor cortex was identified by diffusion tensor imaging (DTI), a simple marker method, and intraoperative electrophysiological measurement. Bony windows were designed by magnetic resonance imaging (MRI) scan and DTI. During the operation, canines in the control group were under general anesthesia. The canines were operated via bony window craniotomy and dura mater opening in the sham group. After opening of the bony window and dura mater, the motor cortex was impacted by a modified electronic cortical contusion impactor (eCCI) in the model group. Results Postoperative measurements revealed damage to the cerebral motor cortex and functional defects. Comparisons between preoperative and postoperative results demonstrated that the established model was successful. Comparison with existing method(s) Compared with conventional models, this is the first brain trauma model in large animal that was constructed based on injury to the cerebral motor cortex under the guidance of DTI, a simple marker method, and electrophysiology. Conclusion The method used to establish this model can be standardized to enhance reproducibility and provide a stable and precise large animal model of TBI for clinical and basic research. [ABSTRACT FROM AUTHOR]