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Advisor(s)
Abstract(s)
Background: Ischemic Stroke (IS) is caused by a focal disruption in cerebral blood flow due to the occlusion of a blood vessel, most commonly the middle cerebral artery (MCA)—the ischemic cascade results in neuronal death and inflammatory response, including in situ microglia activation. Inflammation is a double‐edged sword; it can cause tissue injury but can also help in the tissue repair of the brain. The only approved pharmacological treatment for IS has strong limitations of use depending on the time post-stroke onset. Despite the efforts to develop neuroprotective agents, none have proven efficacious for the human population. Aim: The aim is to clarify the cerebral cellular behavior during the different phases of ischemia-reperfusion as it might contribute to increasing pharmacological targets toward neuroprotection. Methods: The middle cerebral artery occlusion (MCAO) in vivo model was developed (n=8). Rats were randomly divided into two groups: 1) Animals exposed to 1h of ischemia (I1h) and 2) Animals exposed to 1h of ischemia followed by 1h of reperfusion (I/R1h). Brains were collected and the expression of synaptic markers (PSD-95, Syn), inflammatory mediators (TNF-α, IL-1β, IL-10), markers of microglia (Iba1, iNOS, Arg), and astrocytes (GFAP, S100B) were determined by qRealTime-PCR and Western Blot. Results: We found decreased PSD-95 and Syn expression in the ipsilateral hemisphere of both groups (~0.5 fold-I 1h; ~0.5 fold-I/R 1h), compared to the contralateral hemisphere. Levels of IL-10 were decreased in the ipsilateral hemisphere of both groups (~0.2 fold-I 1h; ~0.4 fold-I/R 1h), compared to the contralateral hemisphere. TNF-α was higher in the I/R 1h group compared to the I 1h group. Iba1 and GFAP expression were reduced in the ipsilateral hemisphere of the I/R 1h group (~0.4 fold and 0.8 fold, respectively). Conclusions: Our results strengthen the MCAO rodent model as a potential model to study neuroinflammation as a pharmacological target. Further research is needed to clarify time-dependent changes.
Description
This research was funded by Instituto Politécnico de Lisboa (IPL/2022/MCAO_ESTeSL) and Fundação para a Ciência e a Tecnologia (UIDB/05608/2020 and UIDP/05608/2020).
Keywords
Ischemia Neuroinflammation Reperfusion Stroke IPL/2022/MCAO_ESTeSL UIDB/05608/2020 UIDP/05608/2020
Citation
Mendes P, Solas J, Santos S, Fernandes A, Ratilal B, Mateus V, et al. An in vivo model of ischemic stroke to study potential pharmacological targets. In: Proceedings of Research and Practice in Allied and Environmental Health – 11º Congresso Nacional da APLF. 2023;1(3):24.