Beneficial effects of Kaempferol after developmental TBI is through protection of mitochondrial function, oxidative metabolism and neural viability.

Oxidative energy metabolism is depressed after mild/moderate TBI during early development, accompanied by behavioral debilitation and secondary neuronal death. TBI metabolome analysis revealed broad effects with a striking impact on energy metabolism. Our studies on mitochondrial modulators and their effects on brain function have shown that Kaempferol, a stimulator of the mitochondrial Ca2+ uniporter channel (mCU), enhanced neural and neurovascular activity in the normal and improved stimulus-induced brain activation and behavior after TBI during early development. Since Kaempferol enhances mitochondrial Ca2+ uptake and cycling, with protective effects after TBI, we tested the hypothesis that Kaempferol treatment during the acute/subacute stage after TBI (0-72 hours) acted upon mitochondria in improving TBI outcome. Developmental age rats (P31) were subjected to TBI and treated with vehicle or Kaempferol, (1mg/Kg i.p) in 3 doses at 1, 24 and 48 hours after TBI. Brains were harvested at 72 hours and subjected to Liquid Chromatography Mass Spectrometric (LC/MS) measurements. Decrease in pyruvate and TCA cycle flux were observed in the untreated and vehicle-treated group, consistent with previously established energy metabolic decline after TBI. Kaempferol improved TCA cycle flux, maintained mitochondrial functional integrity as observed by decreased acyl carnitines, improved neural viability as evidenced by higher NAA levels. The positive outcomes of Kaempferol on metabolic profile corresponded with improved sensorimotor behavior.