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Updated: Sep 8, 2026
A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion
Published on: July 17, 2012
Inhibition of TNFalpha attenuates infarct volume and ICAM-1 expression in ischemic mouse brain
1Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor 48109, USA.
Abstract:
The purpose of our study was to determine whether inhibiting the action of tumor necrosis factor-alpha (TNFalpha) attenuates brain injury and reduces inflammatory responses in the mouse during ischemia and reperfusion. Mice underwent middle cerebral artery occlusion (MCAO) for 1 h followed by 23 h reperfusion. Monoclonal neutralizing anti-murine TNFalpha antibody (mAb) was administrated intraventricularly in the mouse with temporary MCAO. Infarct volume in the anti-TNFalpha mAb treated mice was significantly smaller than that in the control group (p < 0.05). The number of intercellular adhesion molecule-1 (ICAM-1)-positive vessels in the ischemic area of the anti-TNFalpha mAb-treated group was significantly less than that in the control group. Our study demonstrated that blocking TNFalpha reduced brain injury and attenuated ICAM-1 expression during transient cerebral ischemia.
Insights
Blocking tumor necrosis factor-alpha (TNFalpha) with an antibody reduced brain injury and inflammation in mice experiencing stroke. This finding suggests TNFalpha inhibition as a potential therapeutic strategy for ischemic brain damage.
Area of Science:
- Neuroscience
- Immunology
- Pathophysiology
Background:
- Ischemia and reperfusion injury significantly impacts brain tissue.
- Inflammatory responses, including tumor necrosis factor-alpha (TNFalpha), play a critical role in ischemic brain damage.
Purpose of the Study:
- To investigate if inhibiting TNFalpha can reduce brain injury and inflammatory responses during cerebral ischemia and reperfusion.
- To evaluate the efficacy of anti-TNFalpha antibody treatment in a mouse model of stroke.
Main Methods:
- A transient middle cerebral artery occlusion (MCAO) model was used in mice for 1 hour followed by 23 hours of reperfusion.
- Intraventricular administration of a monoclonal neutralizing anti-murine TNFalpha antibody (mAb) was performed.
- Infarct volume and intercellular adhesion molecule-1 (ICAM-1) expression were assessed.
Main Results:
- Treatment with anti-TNFalpha mAb significantly reduced infarct volume compared to the control group (p < 0.05).
- The number of ICAM-1-positive vessels in the ischemic area was significantly lower in the anti-TNFalpha mAb-treated group.
- Blocking TNFalpha attenuated inflammatory responses, indicated by reduced ICAM-1 expression.
Conclusions:
- Inhibition of TNFalpha effectively reduces brain injury following transient cerebral ischemia.
- Anti-TNFalpha antibody treatment attenuates inflammatory markers like ICAM-1 during ischemic stroke.
- Targeting TNFalpha presents a promising therapeutic avenue for managing ischemic brain damage.
