Neuroprotective effects of lovastatin against traumatic spinal cord injury in rats

Mirzaie, Jafar; Nasiry, Davood; Ayna, Ömer; Raoofi, Amir; Delbari, Ali; Rustamzadeh, Auob; Nezhadi, Akram; Pur, Zahra Jamal

doi:10.1016/j.jchemneu.2022.102148

Cited by 11 publications

(4 citation statements)

References 52 publications

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“…At the same time, multiple studies have reported caspase-3 activity in non-apoptotic processes (Fernando et al 2002 ; Fujita et al 2008 ; Miura et al 2004 ; Szymczyk et al 2006 ; Woo et al 2003 ). Nevertheless, numerous studies have investigated apoptosis in the spinal cord, especially under pathological conditions, by detecting caspase-3 activation (Dai et al 2019 ; Gülmez et al 2022 ; Mirzaie et al 2022 ; Nesic et al 2001 ; Shen et al 2022 ). On the other hand, studies investigating the apoptotic processes in the intact developing nervous system by employing the commercially available antibodies are lacking.…”

Section: Discussionmentioning

confidence: 99%

“…In the nervous system, apoptosis has been extensively studied because of its crucial role in embryonic development, tissue formation, the function of neuronal circuits (Yuan and Yankner 2000 ), and its involvement in various pathological events linked to neurodegenerative disorders (Erekat 2022 ) and tissue injury (Springer 2002 ). Despite evidence that cC3 is involved in non-apoptotic events, it is commonly used as an apoptotic marker in both older and recent studies of the spinal cord, especially under pathological conditions (Dai et al 2019 ; Gülmez et al 2022 ; Mirzaie et al 2022 ; Nesic et al 2001 ; Shen et al 2022 ). On the other hand, despite the availability of wide range of commercially produced antibodies against various apoptotic markers (including cC3, cPARP, endonuclease G [EndoG], fragmented actin [fractin], cleaved caspase-7 (cC7), etc.…”

Section: Introductionmentioning

confidence: 99%

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Cleaved caspase-3 is present in the majority of glial cells in the intact rat spinal cord during postnatal life

Holota,

Dečmanová,

Alexovič Matiašová

et al. 2023

Histochem Cell Biol

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Cell death is an essential process that occurs during the development of the central nervous system. Despite the availability of a wide range of commercially produced antibodies against various apoptotic markers, data regarding apoptosis in intact spinal cord during postnatal development and adulthood are mostly missing. We investigated apoptosis in rat spinal cord at different stages of ontogenesis (postnatal days 8, 29, and 90). For this purpose, we applied immunofluorescent detection of two widely used apoptotic markers, cleaved caspase-3 (cC3) and cleaved poly(ADP-ribose) polymerase (cPARP). Surprisingly, we found significant discrepancy between the number of cC3+ cells and PARP+ cells, with a ratio between 500:1 and 5000:1 in rat spinal cord at all postnatal time points. The majority of cC3+ cells were glial cells and did not exhibit an apoptotic phenotype. In contrast with in vivo results, in vitro analysis of primary cell cultures derived from neonatal rat spinal cord and treated with the apoptotic inductor staurosporine revealed a similar onset of occurrence of both cC3 and cPARP in cells subjected to apoptosis. Gene expression analysis of spinal cord revealed elevated expression of the Birc4 (XIAP), Birc2, and Birc5 (Survivin) genes, which are known potent inhibitors of apoptosis. Our data indicate that cC3 is not an exclusive marker of apoptosis, especially in glial cells, owing its possible presence in inhibited forms and/or its participation in other non-apoptotic roles. Therefore, cPARP appears to be a more appropriate marker to detect apoptosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cleaved caspase-3 is present in the majority of glial cells in the intact rat spinal cord during postnatal life

Holota,

Dečmanová,

Alexovič Matiašová

et al. 2023

Histochem Cell Biol

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“…Mirzaie et al showed that lovastatin remarkably improved the functional outcomes of SCI treatment by reducing inflammation-induced tissue destruction, neuronal apoptosis, and demyelination post SCI. These findings indicated the neuroprotective role of lovastatin in SCI (124). Lovastatin could inactivate toll-like receptor 4 (TLR4) in microglia by targeting its co-receptor myeloid differentiation protein 2 (MD2) and alleviate neuropathic pain (125).…”

Section: Statinsmentioning

confidence: 92%

The role of immune cells and associated immunological factors in the immune response to spinal cord injury

Tang¹,

Gu²,

Jiang³

et al. 2023

Front. Immunol.

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Spinal cord injury (SCI) is a devastating neurological condition prevalent worldwide. Where the pathological mechanisms underlying SCI are concerned, we can distinguish between primary injury caused by initial mechanical damage and secondary injury characterized by a series of biological responses, such as vascular dysfunction, oxidative stress, neurotransmitter toxicity, lipid peroxidation, and immune-inflammatory response. Secondary injury causes further tissue loss and dysfunction, and the immune response appears to be the key molecular mechanism affecting injured tissue regeneration and functional recovery from SCI. Immune response after SCI involves the activation of different immune cells and the production of immunity-associated chemicals. With the development of new biological technologies, such as transcriptomics, the heterogeneity of immune cells and chemicals can be classified with greater precision. In this review, we focus on the current understanding of the heterogeneity of these immune components and the roles they play in SCI, including reactive astrogliosis and glial scar formation, neutrophil migration, macrophage transformation, resident microglia activation and proliferation, and the humoral immunity mediated by T and B cells. We also summarize findings from clinical trials of immunomodulatory therapies for SCI and briefly review promising therapeutic drugs currently being researched.

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“…Hyperlipidemia is characterized by elevated serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoproteins (LDL-C) along with decreased levels of high-density lipoproteins (HDL-C) . Treatment of dyslipidemia is essential as it is a major contributor to serious diseases such as cardiovascular disease and acute pancreatitis. , Among the therapeutic drugs for hyperlipidemia, atorvastatin calcium, representing statins, is favored for its lipid-lowering effect. − It achieves this by reducing the rate of hepatic cholesterol synthesis through inhibiting the activity of HMG-CoA reductase. However, the application of atorvastatin calcium has also presented challenges, including low water solubility and poor stability.…”

Section: Introductionmentioning

confidence: 99%

Hybrid Microneedle-Mediated Transdermal Delivery of Atorvastatin Calcium-Loaded Polymeric Micelles for Hyperlipidemia Therapy

Ou Yang,

Hu,

Feng

et al. 2024

ACS Appl. Bio Mater.

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Hyperlipidemia has been a huge challenge to global health, leading to the cardiovascular disease, hypertension, and diabetes. Atorvastatin calcium (AC), a widely prescribed drug for hyperlipidemia, faces huge challenges with oral administration due to poor water solubility and hepatic first-pass effects, resulting in low therapeutic efficacy. In this work, we designed and developed a hybrid microneedle (MN) patch system constructed with soluble poly(vinyl alcohol) (PVA) and AC-loaded polymeric micelles (AC@PMs) for transdermal delivery of AC to enhance the hyperlipidemia therapy. We first prepared various AC@PM formulations self-assembled from mPEG–PLA and mPEG–PLA-PEG block copolymers using a dialysis method and evaluated the physicochemical properties in combination with experiment skills and dissipative particle dynamics (DPD) simulations. Then, we encapsulated the AC@PMs into the PVA MN patch using a micromold filling method, followed by characterizing the performances, especially the structural stability, mechanical performance, and biosafety. After conducting in vivo experiments using a hyperlipidemic rat model, our findings revealed that the hybrid microneedle-mediated administration exhibited superior therapeutic efficacy when compared to oral delivery methods. In summary, we have successfully developed a hybrid microneedle (MN) patch system that holds promising potential for the efficient transdermal delivery of hydrophobic drugs.

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Neuroprotective effects of lovastatin against traumatic spinal cord injury in rats

Cited by 11 publications

References 52 publications

Cleaved caspase-3 is present in the majority of glial cells in the intact rat spinal cord during postnatal life

Cleaved caspase-3 is present in the majority of glial cells in the intact rat spinal cord during postnatal life

The role of immune cells and associated immunological factors in the immune response to spinal cord injury

Hybrid Microneedle-Mediated Transdermal Delivery of Atorvastatin Calcium-Loaded Polymeric Micelles for Hyperlipidemia Therapy

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