Heatstroke-induced late-onset neurological deficits in mice caused by Purkinje cell degeneration, demyelination, and synaptic impairment at cerebellum

Abstract Global warming increases the incidence of heatstroke. After heatstroke, patients are bedridden and exhibit neurological symptoms suggesting cerebellar damage. However, the potential long-term adverse outcomes are poorly understood. We studied the cerebellum after heatstroke. In our study, motor coordination disorder significantly appeared 3 weeks post heatstroke and gradually improved to some extent over time. Demyelination was detected at 1 and 3 weeks after heatstroke at the cerebellum. Interestingly, it was not found at the corpus callosum. The Purkinje cell numbers significantly decreased at 1-, 3-, and 9-weeks post heatstroke. The intensity of synaptophysin and postsynaptic density-95 (PSD95) temporarily decreased at 3 weeks post heatstroke; however, both increased at 9 weeks post heatstroke. Motor coordination loss occurred a few weeks after heatstroke and recovered to some extent. Late-onset motor impairment was suggested to be caused by cerebellar dysfunctions that were morphologically assessed by myelin staining and immunostaining of Purkinje cells with pre-and postsynaptic markers. However, the Purkinje cell number did not recover for 9 weeks, the others, including motor coordination were partially recovered probably by synaptic reconstruction, residual Purkinje cells, and other cerebellar neuron remyelination. These phenomena were associated with late-onset neurological deficits and recovery after heatstroke.