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Neuroprotective Effect of Piclamilast-Induced Post-Ischemia Pharmacological Treatment in Mice

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Abstract

Various studies have evidenced the neuroprotective role of PDE4 inhibitors. However, whether PDE4 inhibitor, Piclamilast pharmacological post-treatment is protective during cerebral ischemia reperfusion-induced injury remains unknown. Therefore, this study design included testing the hypothesis that Piclamilast administered at the beginning of a reperfusion phase (Piclamilast pPost-trt) shows protective effects and explores & probes underlying downstream mechanisms. Swiss albino male mice were subjected to global ischemic and reperfusion injury for 17 min. The animals examined cerebral infarct size, biochemical parameters, inflammatory mediators, and motor coordination. For memory, assessment mice were subjected to morris water maze (MWM) and elevated plus maze (EPM) test. Histological changes were assessed using HE staining. Piclamilast pPost-trt significantly reduced I/R injury-induced deleterious effects on biochemical parameters of oxidative stress, inflammatory parameters, infarct size, and histopathological changes, according to the findings. These neuroprotective effects of pPost-trt are significantly abolished by pre-treatment with selective CREB inhibitor, 666–15. Current study concluded that induced neuroprotective benefits of Piclamilast Post-trt, in all probability, maybe mediated through CREB activation. Hence, its neuroprotective effects can be further explored in clinical settings.

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Acknowledgements

The authors are grateful to the Chitkara College of Pharmacy, Chitkara University, Punjab, India for providing the necessary facilities to carry out the research work.

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Authors and Affiliations

  1. Chitkara College of Pharmacy, Chitkara University, Punjab, 140401, India

    Amarjot Kaur, Thakur Gurjeet Singh, Heena Khan, Manish Kumar & Nirmal Singh

  2. Faculty of Veterinary Medicine, Pharmacology Department, Suez Canal University, Ismailia, 41522, Egypt

    Mohamed M. Abdel-Daim

  3. Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, 147002, India

    Nirmal Singh

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Contributions

Amarjot Kaur: AK Thakur Gurjeet Singh: TGS, Heena Khan: HK, Manish Kumar: MN. Conceptualization: AK & TGS, Performed the experiments: AK & HK. Analyzed the data: TGS & MN, Review & editing: AK, NS, TGS & MMAD, Critically reviewed the article: TGS, All authors read and approved the final manuscript. All data were generated in-house and that no paper mill was used.

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Correspondence to Thakur Gurjeet Singh.

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The experimental protocol was conducted and approved as per the guidelines of the Institutional Animal Ethics Committee (IAEC) under registration number: 1181/PO/ReBi/S/08/CPCSEA and the guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Ministry of Environment and Forests, Government of India were followed.

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Kaur, A., Singh, T.G., Khan, H. et al. Neuroprotective Effect of Piclamilast-Induced Post-Ischemia Pharmacological Treatment in Mice. Neurochem Res 47, 2230–2243 (2022). https://doi.org/10.1007/s11064-022-03609-w

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