Pediatrics & Neonatology
Volume 50, Issue 5 , Pages 208-216, October 2009

Human Umbilical Cord Blood Cells Protect Against Hypothalamic Apoptosis and Systemic Inflammation Response During Heatstroke in Rats

  • Won-Shiung Liu

      Affiliations

    • Department of Pediatrics, Chi Mei Medical Center, Tainan, Taiwan
  • ,
  • Chun-Ta Chen

      Affiliations

    • Department of Pediatrics, Chi Mei Medical Center, Tainan, Taiwan
  • ,
  • Ning-Hui Foo

      Affiliations

    • Department of Pediatrics, Chi Mei Medical Center, Tainan, Taiwan
  • ,
  • Hsuan-Rong Huang

      Affiliations

    • Department of Pediatrics, Chi Mei Medical Center, Tainan, Taiwan
  • ,
  • Jhi-Joung Wang

      Affiliations

    • Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
  • ,
  • Sheng-Hsien Chen

      Affiliations

    • Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
    • Department of Obstetrics and Gynecology, Chi Mei Medical Center, Tainan, Taiwan
    • Corresponding Author InformationCorresponding authors. Department of Obstetrics and Gynecology; Department of Pediatrics, Chi Mei Medical Center, 901 Chung Hwa Road, Yung Kang City, Tainan, Taiwan
  • ,
  • Te-Jen Chen

      Affiliations

    • Department of Pediatrics, Chi Mei Medical Center, Tainan, Taiwan
    • Corresponding Author InformationCorresponding authors. Department of Obstetrics and Gynecology; Department of Pediatrics, Chi Mei Medical Center, 901 Chung Hwa Road, Yung Kang City, Tainan, Taiwan

Received 25 November 2008; received in revised form 7 January 2009; accepted 19 January 2009.

Article Outline

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 (0.3 mL per rat, intravenously) or HUCBCs (5 × 106 in 0.3 mL serum-free lymphocyte medium, intravenously). Another group of rats were exposed to room temperature (26°C) and used as normothermic controls. Heatstroke was induced by exposing the anesthetized rats to a high ambient temperature of 43°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.

Key Words:  cytokines , heatstroke , human umbilical cord blood cells , inflammation , rat

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PII: S1875-9572(09)60065-6

doi:10.1016/S1875-9572(09)60065-6

Pediatrics & Neonatology
Volume 50, Issue 5 , Pages 208-216, October 2009