Human umbilical cord blood cells protect against hypothalamic apoptosis and systemic inflammation response during heatstroke in rats.
BACKGROUND
Intravenous administration of human umbilical cord blood cells (HUCBC) has been shown to improve heatstroke by reducing arterial hypotension as well as cerebral ischemia and damage in a rat model. To extend these findings, we assessed both hypothalamic neuronal apoptosis and systemic inflammatory responses in the presence of HUCBCs or vehicle medium immediately after initiation of heatstroke.


METHODS
Anesthetized rats, immediately after the initiation of heat stress, were divided into two groups and given either serum-free lymphocyte medium (0.3mL per rat, intravenously) or HUCBCs (5 x 10(6) in 0.3 mL serum-free lymphocyte medium, intravenously). Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Heatstroke was induced by exposing the anesthetized rats to a high ambient temperature of 43 degrees C for 68 minutes.


RESULTS
After the onset of heatstroke, animals treated with serum-free lymphocyte medium displayed hyperthermia, hypotension, bradycardia, hypothalamic neuronal apoptosis and degeneration, and up-regulation of systemic inflammatory response molecules including serum tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1 and E-selectin. Heatstroke-induced hypotension, bradycardia, hypothalamic neuronal apoptosis and degeneration, and increased systemic inflammatory response molecules were significantly inhibited by HUCBC treatment. Although heatstroke-induced hyperthermia was not affected by HUCBC treatment, the serum levels of the anti-inflammatory cytokine interleukin-10 were significantly increased by HUCBC therapy during hyperthermia.


CONCLUSIONS
These findings suggest that HUCBC transplantation may prevent the occurrence of heatstroke by reducing hypothalamic neuronal damage and the systemic inflammatory responses.
Department of Pediatrics, Chi Mei Medical Center, Tainan, Taiwan.
Won-Shiung
WS
Liu
Chun-Ta
CT
Chen
Ning-Hui
NH
Foo
Hsuan-Rong
HR
Huang
Jhi-Joung
JJ
Wang
Sheng-Hsien
SH
Chen
Te-Jen
TJ
Chen
D000818:Animals; D017209:Apoptosis; D036101:Cord Blood Stem Cell Transplantation; D019040:E-Selectin / Q000097:blood; D018883:Heat Stroke / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007022:Hypotension / Q000628:therapy; D007031:Hypothalamus / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D016753:Interleukin-10; D009410:Nerve Degeneration; D051381:Rats; D017207:Rats, Sprague-Dawley; D018746:Systemic Inflammatory Response Syndrome / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10