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Updated: Jul 18, 2026
Two-vessel Occlusion Mouse Model of Cerebral Ischemia-reperfusion
Published on: March 1, 2019
Reduced cerebral ischemia-reperfusion injury in Toll-like receptor 4 deficient mice
Can-Xiang Cao1, Qing-Wu Yang, Feng-Lin Lv
1Department of Neurology, DaPing Hospital, The Third Military Medical University, ChangJiang Branch Road 10, DaPing, YuZhong District, Chongqing 400042, China.
Abstract:
Inflammatory reaction plays an important role in cerebral ischemia-reperfusion injury, however, its mechanism is still unclear. Our study aims to explore the function of Toll-like receptor 4 (TLR4) in the process of cerebral ischemia-reperfusion. We made middle cerebral artery ischemia-reperfusion model in mice with line embolism method. Compared with C3H/OuJ mice, scores of cerebral water content, cerebral infarct size and neurologic impairment in C3H/Hej mice were obviously lower after 6 h ischemia and 24 h reperfusion. Light microscopic and electron microscopic results showed that cerebral ischemia-reperfusion injury in C3H/Hej mice was less serious than that in C3H/OuJ mice. TNF-alpha and IL-6 contents in C3H/HeJ mice were obviously lower than that in C3H/OuJ mice with ELISA. The results showed that TLR4 participates in the process of cerebral ischemia-reperfusion injury probably through decrease of inflammatory cytokines. TLR4 may become a new target for prevention of cerebral ischemia-reperfusion injury. Our study suggests that TLR4 is one of the mechanisms of cerebral ischemia-reperfusion injury besides its important role in innate immunity.
Insights
Toll-like receptor 4 (TLR4) activation exacerbates cerebral ischemia-reperfusion injury by increasing inflammatory cytokines. Inhibiting TLR4 may offer a novel therapeutic strategy for stroke by reducing brain damage and neurological deficits.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Cerebral ischemia-reperfusion injury involves significant inflammatory responses.
- The precise mechanisms underlying this inflammation, particularly the role of specific receptors, remain incompletely understood.
Purpose of the Study:
- To investigate the role of Toll-like receptor 4 (TLR4) in the pathogenesis of cerebral ischemia-reperfusion injury.
- To explore whether TLR4 influences inflammatory cytokine production and subsequent brain damage.
Main Methods:
- A middle cerebral artery occlusion/reperfusion model was established in mice.
- Comparison of injury severity (cerebral water content, infarct size, neurological deficits) between C3H/Hej (TLR4-deficient) and C3H/OuJ (TLR4-sufficient) mice.
- Histopathological analysis using light and electron microscopy.
- Quantification of inflammatory cytokines (TNF-alpha, IL-6) via ELISA.
Main Results:
- C3H/Hej mice exhibited significantly reduced cerebral water content, infarct size, and neurological impairment compared to C3H/OuJ mice.
- Histopathological examination revealed less severe injury in C3H/Hej mice.
- Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels were markedly lower in C3H/Hej mice.
Conclusions:
- Toll-like receptor 4 (TLR4) plays a crucial role in exacerbating cerebral ischemia-reperfusion injury.
- TLR4 appears to mediate injury, at least in part, by promoting the release of inflammatory cytokines like TNF-alpha and IL-6.
- Targeting TLR4 presents a potential therapeutic avenue for mitigating brain damage following ischemic stroke.
