Oxiracetam alleviates anti-inflammatory activity and ameliorates cognitive impairment in the early phase of traumatic brain injury

Youn, Dong Hyuk; Han, Sung Woo; Kim, Jong-Tae; Choi, Hyeong‐Ah; Lee, A Ran; Kim, Nayoung; Jung, Harry; Hong, Eun Pyo; Park, Chan Hum; Lee, Younghyurk; Cho, Sung Min; Jeon, Jin Pyeong

doi:10.1007/s00701-023-05674-8

Cited by 5 publications

(3 citation statements)

References 40 publications

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“…Studies have shown that intraperitoneal injection of oxiracetam can improve the performance of TBI mice in water maze and Y maze experiments and reduce inflammation and apoptosis markers in brain tissue. 35 Similarly, intragastric administration with oxiracetam in TBI rats has yielded similar behavioral results. 36 Overall, oxiracetam is an effective class of nootropic drugs with established efficacy and good patient tolerance.…”

Section: Discussionmentioning

confidence: 86%

“…However, research on the effects of oxiracetam and its enantiomers after TBI is limited. Studies have shown that intraperitoneal injection of oxiracetam can improve the performance of TBI mice in water maze and Y maze experiments and reduce inflammation and apoptosis markers in brain tissue 35 . Similarly, intragastric administration with oxiracetam in TBI rats has yielded similar behavioral results 36 .…”

Section: Discussionmentioning

confidence: 91%

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Effect of L‐oxiracetam and oxiracetam on memory and cognitive impairment in mild‐to‐moderate traumatic brain injury patients: Study protocol for a randomized controlled trial

Liu,

Nie

et al. 2024

Aging Medicine

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ObjectivesPatients 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.MethodsThe 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.DiscussionThere 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 registrationchinadrugtrials.org.cn, identifier CTR20192539; ClinicalTrials.gov, identifier NCT04205565.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 91%

Effect of L‐oxiracetam and oxiracetam on memory and cognitive impairment in mild‐to‐moderate traumatic brain injury patients: Study protocol for a randomized controlled trial

Liu,

Nie

et al. 2024

Aging Medicine

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“…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].…”

Section: Discussionmentioning

confidence: 99%

In Silico Analysis: Anti-Inflammatory and α-Glucosidase Inhibitory Activity of New α-Methylene-γ-Lactams

Hernández-Guadarrama,

Díaz-Román,

Linzaga-Elizalde

et al. 2024

Molecules

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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.

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Exploring the effects of moxibustion on cognitive function in rats with multiple cerebral infarctions from the perspective of glial vascular unit repairing

Wang,

Du,

Liu

et al. 2024

Front. Pharmacol.

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ObjectiveThis study aimed to explore the effect of moxibustion at Governor Vessel (GV) acupoints, including Baihui (GV 20), Shenting (GV 24) and Dazhui (GV 14) for 14 days on glial vascular unit (GVU) in rats with multiple microinfarctions (MMI), and to explore its action mechanism.MethodsThe effect and mechanism of moxibustion on vascular dementia (VD) were studied in MMI rats by means of behavioral and molecular biology experiments.ResultsRats receiving MMI showed impairment of memory function, reduction of cerebral blood flow, damage of blood-brain barrier (BBB) integrity and increased brain mass. MMI also increased neuronal degeneration in the hippocampus. Notably, levels of glial fibrillary acidic protein (GFAP) and complement component 3 significantly increased, but those of Connexin43 (CX43) and platelet derived growth factor receptor β (PDGFRβ) significantly decreased in the hippocampus of the rats receiving MMI. Moxibustion, as well as oxiracetam (ORC) treatment improved memory function and neuronal degeneration, ameliorated BBB integrity, increased cerebral blood flow and decreased brain mass. In addition, moxibustion as well as oxiracetam (ORC) treatment reduced the decrease of CX43 protein and increased PDGFRβ protein level in the hippocampus of MMI rats. Moreover, moxibustion treatment reversed MMI-induced increase of the GFAP/CX43 ratio in vascular structural units. Importantly, after PDGFRβ inhibition, VD rats treated with moxibustion had impaired learning and memory, decreased cerebral blood flow, and BBB disruption.ConclusionMoxibustion treatment at various GV acupoints improved cerebral blood flow and repaired BBB function in rats with MMI, likely through protecting GVU.

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Oxiracetam alleviates anti-inflammatory activity and ameliorates cognitive impairment in the early phase of traumatic brain injury

Cited by 5 publications

References 40 publications

Effect of L‐oxiracetam and oxiracetam on memory and cognitive impairment in mild‐to‐moderate traumatic brain injury patients: Study protocol for a randomized controlled trial

Effect of L‐oxiracetam and oxiracetam on memory and cognitive impairment in mild‐to‐moderate traumatic brain injury patients: Study protocol for a randomized controlled trial

In Silico Analysis: Anti-Inflammatory and α-Glucosidase Inhibitory Activity of New α-Methylene-γ-Lactams

Exploring the effects of moxibustion on cognitive function in rats with multiple cerebral infarctions from the perspective of glial vascular unit repairing

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