Triiodothyronine ameliorates S-ketamine-induced hypomyelination via the PPARα pathway in neonatal rat.
Experimental neurology July 1, 2025 Mengqin Shan, Chaoyang Tong, Xin Fu et al. 2 citations
S-ketamine anesthesia in neonatal rats causes a drop in thyroid hormone levels and disrupts myelination, particularly by impairing the differentiation of oligodendrocyte precursor cells into mature oligodendrocytes. This leads to motor coordination deficits. Supplementing with triiodothyronine (T3) reverses these effects by restoring PPARα activity, a key regulator of lipid metabolism. Blocking PPARα with GW6471 eliminates T3's protective effect, while activating PPARα with fenofibrate rescues both coordination and cell maturation. The findings suggest that thyroid hormone supplementation could prevent anesthesia-related white matter damage in infants.