Ischemic and oxidative damage to the hypothalamus may be associated with decreased heat tolerance as well as
heatstroke formation. The present study explores the hypothalamic
proteome mechanisms associated with
heatstroke-mediated hypothalamic
ischemia, and oxidative damage.
Heatstroke rats had
hypotension, hypothalamic
ischemia, and lethality. In addition, they had
hyperthermia and hypothalamic blood-brain-barrier disruption, oxidative stress, activated
inflammation, and neuronal apoptosis and degeneration. 2DE combined LC-MS/MS revealed that
heatstroke-induced ischemic injury and apoptosis were associated with upregulation of
L-lactate dehydrogenase but downregulation of both dihydropyriminase-related
protein and 14-3-3 Zeta
isoform protein. Heat-induced blood-brain-barrier disruption might be related to upregulation of
glial fibrillary acidic protein. Oxidative stress caused by
heatstroke might be related to upregulation of cytosolic dehydrogenase-1. Also, heat-induced overproduction of proinflammatory
cytokines might be associated with downregulation of
stathmin 1. Heat-induced hypothalamic
ischemia, apoptosis, injury (or upregulation of
L-lactate dehydrogenase), blood-brain-barrier disruption (or upregulation of
glial fibrillary acidic protein), oxidative stress (or upregulation of cytosolic
dehydrogenase-1), and activated
inflammation (or downregulation of
stathmin 1) were all significantly reversed by whole body cooling. Our data indicate that cooling
therapy improves outcomes of
heatstroke by modulating hypothalamic
proteome mechanisms.