6, ICAM-1 1.9 �� 0.7-fold Wortmannin side effects compared with sham control) and IL-1�� protein concentration (1.3 �� 0.4-fold compared with sham control). Sevoflurane did not confer statistically significant (versus hypothermia) additional protective effects neither on mRNA (IL-1�� 1.2 �� 0.6, IL-6 2.0 �� 0.9, IL-10 0.7 �� 0.3, TNF�� 0.9 �� 0.4, ICAM-1 1.8 �� 0.6-fold compared with sham control) nor on protein levels (1.1 �� 0.2-fold compared with sham control; Figures Figures22 and and33).Figure 2Cerebral cytokine mRNA expression. Transcript levels of the cerebral cytokines interleukin (IL)-1��, IL-6, IL-10, tumor necrosis factor (TNF)�� and intercellular adhesion molecule (ICAM)-1 were determined by quantitative RT-PCR. NT, normothermia; …Figure 3Protein concentration of interleukin-1��.
Protein concentration of interleukin (IL)-1�� was determined by a swine specific enzyme-linked-immunosorbent assay. NT, normothermia; HT, hypothermia; HT+SEV, hypothermia combined with sevoflurane. …Bax and Bcl-2 mRNA expressionWe found a significant (P < 0.01) upregulation of both Bcl-2 mRNA and Bax expression after global cerebral ischemia (NT: Bcl-2 3.2 �� 1.8-fold, Bax 2.3 �� 1.3-fold compared with sham control). Hypothermia was associated with significantly (P < 0.05) less upregulation of mRNA expression (Bcl-2 1.2 �� 0.5-fold, Bax 1.2 �� 0.6-fold compared with sham control). Sevoflurane did not confer additional effects (Bcl-2 1.1 �� 0.4-fold, Bax 1.1 �� 0.4-fold compared with sham control; Figure Figure44).Figure 4Cerebral Bcl-2 and Bax mRNA expression.
Transcript levels of the cerebral apoptosis-associated proteins Bcl-2 and Bax were determined by quantitative RT-PCR. NT, normothermia; HT, hypothermia; HT+SEV, hypothermia combined with sevoflurane. Data are expressed …DiscussionNeurological dysfunction resulting from cardiac arrest largely contributes to morbidity and mortality after initially successful CPR [21]. Employing a pig model we showed that (i) global cerebral ischemia following cardiac arrest and CPR results in upregulation of pro-inflammatory cytokine expression in the cerebral tissue, ii) mild hypothermia significantly reduces cerebral tissue inflammatory response, and (iii) pharmacological post-conditioning with sevoflurane does not confer additional anti-inflammatory effects on cerebral tissue.
Cerebral inflammatory response following resuscitationMechanisms of brain injury following cerebral ischemia are complex with multiple modulators, Drug_discovery signaling pathways, proteins and enzymes being involved that may facilitate cell death or survival [22]. Post-ischemic inflammation has been shown to play a critical role in cerebral ischemia/reperfusion injury [23]. Specifically, there is strong evidence suggesting that a disproportionate and persistent production of cytokines can significantly increase the risk and extent of brain injury [5,24].