Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Oct;32(10):1939-47.
doi: 10.1038/jcbfm.2012.99. Epub 2012 Jul 11.

Effects of therapeutic hypothermia on inflammasome signaling after traumatic brain injury

Satoshi Tomura  1 , Juan Pablo de Rivero Vaccari, Robert W Keane, Helen M Bramlett, W Dalton Dietrich
Affiliations

Effects of therapeutic hypothermia on inflammasome signaling after traumatic brain injury

Satoshi Tomura et al. J Cereb Blood Flow Metab. 2012 Oct.

Abstract

Traumatic brain injury (TBI) activates the NALP1/NLRP1 inflammasome, which is an important component of the early innate inflammatory response to injury. We investigated the influence of therapeutic hypothermia on inflammasome activation after TBI. Adult male Sprague-Dawley rats were subjected to moderate fluid percussion brain injury. Temperature manipulation (33°C or 37°C) was initiated 30 minutes after TBI and maintained for 4 hours. At 4 or 24 hours after TBI, traumatized cortex and hippocampus were prepared for immunoblot or immunohistochemical analysis. In the normothermic groups, caspase-1, caspase-11 and expression of the purinergic receptor P2X7 increased at 24 hours after TBI. Posttraumatic hypothermia lead to decreased expression of these proteins at 24 hours compared with normothermic levels. Immunocytochemical studies showed that posttraumatic hypothermia also decreased caspase-1 staining in cerebral cortical neurons compared with normothermic TBI. Cultured cortical neurons subjected to stretch injury demonstrated significant secretion of caspase-1 into the culture medium and caspase-3 activation, both results reduced by hypothermic treatment. Posttraumatic hypothermia decreases inflammasome signaling in neurons and reduces the innate immune response to TBI at 24 hours after injury. Therapeutic hypothermia may protect the injured central nervous system by targeting the detrimental consequences of the innate immune response to injury.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Hypothermia reduces interleukin (IL)-1β processing in the injured cortex at 24 hours after traumatic brain injury (TBI). Immunoblot analysis of IL-1β in lysates of cortex (A) or hippocampus (B) of sham-operated animals (Sh), normothermic group (N), and hypothermic group (H) at 4 and 24 hours after injury. β-Actin was used as internal standard and control for protein loading. Data are expressed as mean±s.e.m. *P<0.05. N=6 per group.
Figure 2
Figure 2
Hypothermia reduces caspase-1 and caspase-11 processing independently of ASC in the injured cortex at 24 hours after traumatic brain injury (TBI). Representative immunoblots of cortical lysates of sham-operated animals (sh), normothermic group (N), and hypothermic group (H) at 4 and 24 hours after injury. Representative immunoblots of caspase-1 (A), caspase-11 (B), and ASC (C). β-Actin was used as internal standard and control for protein loading. Data are expressed as mean±s.e.m. *P<0.05. N=5 to 6 per group.
Figure 3
Figure 3
Hypothermia does not affect inflammasome protein expression in the injured hippocampus. Representative immunoblots of lysates of hippocampus of sham-operated animals (sh), normothermic group (N), and hypothermic group (H) at 4 and 24 hours after injury. Representative immunoblots of caspase-1 (A), caspase-11, (B) and ASC (C). β-Actin was used as internal standard and control for protein loading. Data are expressed as mean±s.e.m. N=6 per group.
Figure 4
Figure 4
Hypothermia reduces caspase-1 expression in neurons in the injured cortex at 24 hours after traumatic brain injury (TBI). Confocal images show cortex neurons of sham, normothermic group, and hypothermic group. Sections were stained for neurons (green) and caspase-1 (red).
Figure 5
Figure 5
Hypothermia reduces P2X7R expression in the cortex after TBI. (A) Representative immunoblot of cortical lysates for P2X7R. (B) Immunoblot analysis of P2X7 receptor in lysates of cortex of sham-operated animals (Sh), normothermic group (N) and hypothermic group (H) at 4 h and 24 h after injury. β-Actin was used as internal standard and control for protein loading. Data are expressed as mean±s.e.m. *P<0.05. N=5–6 per group.
Figure 6
Figure 6
Hypothermia reduces active caspase-1 expression in the media of stretched injured neurons and caspase-3 activation is decreased by hypothermia in stretched injured neurons. Immunoblot analysis of caspase-1 in the media of cortical neurons grown in culture (A) and caspase-3 in neuronal cell lysates (B) of stretch-injured neurons in normothermia (N) and after 2 hours hypothermia (H). β-Actin was used as internal standard and control for protein loading. Data are expressed as mean±s.e.m. *P<0.05. N=6 per group.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abulafia DP, de Rivero Vaccari JP, Lozano JD, Lotocki G, Keane RW, Dietrich WD. Inhibition of the inflammasome complex reduces the inflammatory response after thromboembolic stroke in mice. J Cereb Blood Flow Metab. 2009;29:534–544. - PubMed
    1. Bramlett HM, Dietrich WD. Progressive damage after brain and spinal cord injury: pathomechanisms and treatment strategies. Prog Brain Res. 2007;161:125–141. - PubMed
    1. Buttram SD, Wisniewski SR, Jackson EK, Adelson PD, Feldman K, Bayir H, Berger RP, Clark RS, Kochanek PM. Multiplex assessment of cytokine and chemokine levels in cerebrospinal fluid following severe pediatric traumatic brain injury: effects of moderate hypothermia. J Neurotrauma. 2007;24:1707–1717. - PubMed
    1. Chatzipanteli K, Alonso OF, Kraydieh S, Dietrich WD. Importance of posttraumatic hypothermia and hyperthermia on the inflammatory response after fluid percussion brain injury: biochemical and immunocytochemical studies. J Cereb Blood Flow Metab. 2000;20:531–542. - PubMed
    1. Ciallella JR, Ikonomovic MD, Paljug WR, Wilbur YI, Dixon CE, Kochanek PM, Marion DW, DeKosky ST. Changes in expression of amyloid precursor protein and interleukin-1beta after experimental traumatic brain injury in rats. J Neurotrauma. 2002;19:1555–1567. - PubMed

Publication types