Figure - available from: Acta Neurochirurgica
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Results of the in vivo study. (A and B) Optical visible image of a mouse brain, TTC-sectioned coronal mouse brain, and brain water content. (C and D) Representative images of FJB-positive and TUNEL-positive cells. Scale bar is 200 μm. (E–H) mRNA expression of COX-2, NLRP3, caspase-1, and IL-1β by qRT-PCR. (I) Western blotting of COX-2, NLRP3, caspase-1, and IL-1β. (J and K) Representative images of injured cortical lesions with double-immunofluorescence staining for COX-2, NLRP3, caspase-1, IL-1β (red), and Iba-1 or GFAP (green), then stained with DAPI. Scale bar is 400 μm. Error bars, mean SEM, *P < 0.05, ** P < 0.01, and *** P < 0.005. TBI indicates traumatic brain injury; ORC, oxiracetam
Source publication
Background
We aimed to investigate the effects of oxiracetam on cognitive impairment in the early phase of traumatic brain injury (TBI), for which no specific treatment is currently available.
Methods
The in vitro study used a cell injury controller to damage SH-SY5Y cells and evaluate the effect of oxiracetam at a dosage of 100 nM. The in vivo st...
Citations
... Currently, several drugs are γ-lactams derivatives, including doxapram, rolipram, and racetams [31,32]. Some studies have demonstrated their anti-inflammatory properties associated with the suppression of pro-inflammatory cytokines through different mechanisms [33][34][35][36]. α-methylene-γ-lactams are a subclass of γ-lactams that have shown potential as anti-inflammatory agents [37]. ...
The research about α-methylene-γ-lactams is scarce; however, their synthesis has emerged in recent years mainly because they are isosters of α-methylene-γ-lactones. This last kind of compound is structurally most common in some natural products’ nuclei, like sesquiterpene lactones that show biological activity such as anti-inflammatory, anticancer, antibacterial, etc., effects. In this work, seven α-methylene-γ-lactams were evaluated by their inflammation and α-glucosidase inhibition. Thus, compounds 3-methylene-4-phenylpyrrolidin-2-one (1), 3-methylene-4-(p-tolyl)pyrrolidin-2-one (2), 4-(4-chlorophenyl)-3-methylenepyrrolidin-2-one (3), 4-(2-chlorophenyl)-3-methylenepyrrolidin-2-one (4), 5-ethyl-3-methylene-4-phenylpyrrolidin-2-one (5), 5-ethyl-3-methylene-4-(p-tolyl)pyrrolidin-2-one (6) and 4-(4-chlorophenyl)-5-ethyl-3-methylenepyrrolidin-2-one (7) were evaluated via in vitro α-glucosidase assay at 1 mM concentration. From this analysis, 7 exerts the best inhibitory effect on α-glucosidase compared with the vehicle, but it shows a low potency compared with the reference drug at the same dose. On the other side, inflammation edema was induced using TPA (12-O-tetradecanoylphorbol 13-acetate) on mouse ears; compounds 1–7 were tested at 10 µg/ear dose. As a result, 1, 3, and 5 show a better inhibition than indomethacin, at the same doses. This is a preliminary report about the biological activity of these new α-methylene-γ-lactams.
Objectives
Patients with traumatic brain injury (TBI) often suffer memory and cognitive impairments, and oxiracetam‐like drugs are considered to have a positive impact on these symptoms potentially. However, the efficacy and safety of l‐oxiracetam and oxiracetam in TBI patients have not been sufficiently investigated.
Methods
The study adopts a multicenter, randomized, double‐blind, parallel‐group, phase 3 clinical trial design in 74 centers across 51 hospitals in China. A total of 590 TBI patients meeting criteria will be randomly allocated into three groups in a 2:2:1 ratio: l‐oxiracetam group, oxiracetam group, and placebo group. The treatment period is 14 days, with a follow‐up period of 90 days. The primary outcome measure is the change in the Loewenstein Occupational Therapy Cognitive Assessment score at 90 days after treatment. Secondary outcomes include changes in other cognitive assessments, neurological function, activities of daily living, and safety assessments.
Discussion
There is no robust evidence to suggest that l‐oxiracetam and oxiracetam can enhance memory and cognitive function in patients with mild to moderate TBI. This study has the potential to answer this crucial clinical question.
Trial registration
chinadrugtrials.org.cn, identifier CTR20192539; ClinicalTrials.gov, identifier NCT04205565.
