The 70 kDa heat shock protein protects against experimental traumatic brain injury

Jong Youl Kim, Nuri Kim, Zhen Zheng, Jongeun Lee, Midori A. Yenari

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Traumatic brain injury (TBI) causes disruption of the blood brain barrier (BBB) leading to hemorrhage which can complicate an already catastrophic illness. Matrix metalloproteinases (MMPs) involved in the breakdown of the extracellular matrix may lead to brain hemorrhage. We explore the contribution of the 70 kDa heat shock protein (Hsp70) to outcome and brain hemorrhage in a model of TBI. Male, wildtype (Wt), Hsp70 knockout (Ko) and transgenic (Tg) mice were subjected to TBI using controlled cortical impact (CCI). Motor function, brain hemorrhage and lesion size were assessed at 3, 7 and 14 days. Brains were evaluated for the effects of Hsp70 on MMPs.In Hsp70 Tg mice, CCI led to smaller brain lesions, decreased hemorrhage and reduced expression and activation of MMPs compared to Wt. CCI also significantly decreased right-biased swings and corner turns in the Hsp70 Tg mice. Conversely, Hsp70 Ko mice had significantly increased lesion size, worsened brain hemorrhage and increased expression and activation of MMPs with worsened behavioral outcomes compared to Wt. Hsp70 is protective in experimental TBI. To our knowledge, this is the direct demonstration of brain protection by Hsp70 in a TBI model. Our data demonstrate a new mechanism linking TBI-induced hemorrhage and neuronal injury to the suppression of MMPs by Hsp70, and support the development of Hsp70 enhancing strategies for the treatment of TBI.

Original languageEnglish
Pages (from-to)289-295
Number of pages7
JournalNeurobiology of Disease
Volume58
DOIs
Publication statusPublished - 2013 Jan 1

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HSP70 Heat-Shock Proteins
Matrix Metalloproteinases
Intracranial Hemorrhages
Transgenic Mice
Hemorrhage
Knockout Mice
Catastrophic Illness
Brain
Traumatic Brain Injury
Blood-Brain Barrier
Extracellular Matrix
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Neurology

Cite this

Kim, Jong Youl ; Kim, Nuri ; Zheng, Zhen ; Lee, Jongeun ; Yenari, Midori A. / The 70 kDa heat shock protein protects against experimental traumatic brain injury. In: Neurobiology of Disease. 2013 ; Vol. 58. pp. 289-295.
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The 70 kDa heat shock protein protects against experimental traumatic brain injury. / Kim, Jong Youl; Kim, Nuri; Zheng, Zhen; Lee, Jongeun; Yenari, Midori A.

In: Neurobiology of Disease, Vol. 58, 01.01.2013, p. 289-295.

Research output: Contribution to journalArticle

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