title: Delayed profound local brain hypothermia markedly reduces interleukin-1beta gene expression and vasogenic edema development in a porcine model of intracerebral hemorrhage.
abstract: White matter (lobar) intracerebral hemorrhage (ICH) can cause edema-related deaths and life-long morbidity. In our porcine model, ICH induces oxidative stress, acute interstitial and delayed vasogenic edema, and up-regulates interleukin-1beta (IL-1beta), a proinflammatory cytokine-linked to blood-brain barrier (BBB) opening. In brain injury models, hypothermia reduces inflammatory cytokine production and protects the BBB. Clinically, however, hypothermia for stroke treatment using surface and systemic approaches can be challenging. We tested the hypothesis that an alternative approach, i.e., local brain cooling using the ChillerPad System, would reduce IL-1beta gene expression and vasogenic edema development even if initiated several hours after ICH. We infused autologous whole blood (3.0 mL) into the frontal hemispheric white matter of 20 kg pentobarbital-anesthetized pigs. At 3 hours post-ICH, we performed a craniotomy for epidural placement of the ChillerPad. Chilled saline was then circulated through the pad for 12 hours to induce profound local hypothermia (14 degrees C brain surface temperature). We froze brains in situ at 16 hours after ICH induction, sampled perihematomal white matter, extracted RNA, and performed real-time RT-PCR. Local brain cooling markedly reduced both IL-1beta RNA levels and vasogenic edema. These robust results support the potential for local brain cooling to protect the BBB and reduce injury after ICH.
authors: Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH, USA. wagnerkr@email.uc.edu
authors: K R
authors: KR
authors: Wagner
authors: S
authors: S
authors: Beiler
authors: C
authors: C
authors: Beiler
authors: J
authors: J
authors: Kirkman
authors: K
authors: K
authors: Casey
authors: T
authors: T
authors: Robinson
authors: D
authors: D
authors: Larnard
authors: G M
authors: GM
authors: de Courten-Myers
authors: M J
authors: MJ
authors: Linke
authors: M
authors: M
authors: Zuccarello