Experimental neurology · 2026
Morphology matters: Spherical versus rod-shaped selenium nanoparticles exert divergent neuroprotection after cerebral ischemia/reperfusion via redox reprogramming and mitochondrial bioenergetics.
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Semernya Elena P, Varlamova Elena G, Sariev Anvar, Nebesnaya Kamila S, Charishnikova Oksana S, Abramova Anastasia A, Baimler Ilya V, Gudkov Sergey V, Baev Artyom Y, Turovsky Egor A
Аннотация
BACKGROUND: Ischemic stroke is a leading cause of death and disability, with reperfusion injury-driven oxidative stress representing a key therapeutic target. Selenium nanoparticles (SeNPs) show neuroprotective potential, yet the influence of nanoparticle morphology remains poorly understood.
OBJECTIVE: To compare the neuroprotective effects of spherical (Sph) versus rod-shaped (Rods) SeNPs in models of cerebral ischemia/reperfusion, focusing on redox modulation, mitochondrial bioenergetics, and functional outcomes.
METHODS: Primary rat cortical neuron-astrocyte co-cultures were exposed to Sph or Rods (1-10 μg/mL). ROS production, mitochondrial membrane potential, cell viability, gene expression, and neurite outgrowth were assessed. In vivo, transient middle cerebral artery occlusion (tMCAO) was induced in rats, followed by intraperitoneal injection of Sph or Rods (1 μg/g) 1 h post-reperfusion. Neurological outcomes and infarct volume were evaluated at 24 and 48 h.
RESULTS: Low concentrations (1-5 μg/mL) of both morphologies upregulated antioxidant genes, suppressed pro-apoptotic factors, enhanced Bcl2 expression, and promoted neuritogenesis without cytotoxicity. High concentration (10 μg/mL) induced pro-oxidant shift, with Sph triggering early apoptosis and Rods causing late apoptosis/necrosis. Both SeNPs restored CO-induced ΔΨm collapse and normalized respiratory chain function. In vivo, Sph improved motor coordination without reducing infarct volume, whereas Rods significantly reduced infarct size but showed less sustained behavioral improvement.
CONCLUSIONS: Nanoparticle morphology critically dictates therapeutic strategy: spherical SeNPs prioritize functional preservation, whereas nanorods confer structural tissue salvage. These findings establish morphology as a key determinant of SeNPs bioactivity and provide a rationale for morphology-guided design of nanotherapeutics for ischemic stroke.
OBJECTIVE: To compare the neuroprotective effects of spherical (Sph) versus rod-shaped (Rods) SeNPs in models of cerebral ischemia/reperfusion, focusing on redox modulation, mitochondrial bioenergetics, and functional outcomes.
METHODS: Primary rat cortical neuron-astrocyte co-cultures were exposed to Sph or Rods (1-10 μg/mL). ROS production, mitochondrial membrane potential, cell viability, gene expression, and neurite outgrowth were assessed. In vivo, transient middle cerebral artery occlusion (tMCAO) was induced in rats, followed by intraperitoneal injection of Sph or Rods (1 μg/g) 1 h post-reperfusion. Neurological outcomes and infarct volume were evaluated at 24 and 48 h.
RESULTS: Low concentrations (1-5 μg/mL) of both morphologies upregulated antioxidant genes, suppressed pro-apoptotic factors, enhanced Bcl2 expression, and promoted neuritogenesis without cytotoxicity. High concentration (10 μg/mL) induced pro-oxidant shift, with Sph triggering early apoptosis and Rods causing late apoptosis/necrosis. Both SeNPs restored CO-induced ΔΨm collapse and normalized respiratory chain function. In vivo, Sph improved motor coordination without reducing infarct volume, whereas Rods significantly reduced infarct size but showed less sustained behavioral improvement.
CONCLUSIONS: Nanoparticle morphology critically dictates therapeutic strategy: spherical SeNPs prioritize functional preservation, whereas nanorods confer structural tissue salvage. These findings establish morphology as a key determinant of SeNPs bioactivity and provide a rationale for morphology-guided design of nanotherapeutics for ischemic stroke.