&lt;p&gt;Antiapoptotic and Anti-Inflammatory Effects of CPCGI in Rats with Traumatic Brain Injury&lt;/p&gt;

Niu, Fei; Ke, Qing; Qi, Hongyan; Zhao, Yijie; Jiang, Yingying; Sun, Ming

doi:10.2147/ndt.s281530

Cited by 8 publications

(5 citation statements)

References 38 publications

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“…Acute elevations (2 h–5 days) in UCH-L1 ( Liu et al, 2010 ; Osier et al, 2021 ) and NF-L ( Korley et al, 2018 ; Karlsson et al, 2021 ) levels were previously detected in serum and CSF post-TBI. The earliest time at which changes in GFAP levels in injured brain tissue was detected is 3 days post-TBI ( Wang et al, 2018 ; Niu et al, 2020 ), and our results are consistent with that. One of our aims in this study was to evaluate the effect of mTBI on injury markers in injured tissue at 3 h post-TBI.…”

Section: Discussionsupporting

confidence: 92%

The Nociceptin/Orphanin FQ peptide receptor antagonist, SB-612111, improves cerebral blood flow in a rat model of traumatic brain injury

Al Yacoub,

Tarantini,

Zhang

et al. 2023

Front. Pharmacol.

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Traumatic brain injury (TBI) affects more than 2.5 million people in the U.S. each year and is the leading cause of death and disability in children and adults ages 1 to 44. Approximately 90% of TBI cases are classified as mild but may still lead to acute detrimental effects such as impaired cerebral blood flow (CBF) that result in prolonged impacts on brain function and quality of life in up to 15% of patients. We previously reported that nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor antagonism reversed mild blast TBI-induced vestibulomotor deficits and prevented hypoxia. To explore mechanisms by which the NOP receptor-N/OFQ pathway modulates hypoxia and other TBI sequelae, the ability of the NOP antagonist, SB-612111 (SB), to reverse TBI-induced CBF and associated injury marker changes were tested in this study. Male Wistar rats randomly received sham craniotomy or craniotomy + TBI via controlled cortical impact. Injury severity was assessed after 1 h (modified neurological severity score (mNSS). Changes in CBF were assessed 2 h post-injury above the exposed cortex using laser speckle contrast imaging in response to the direct application of increasing concentrations of vehicle or SB (1, 10, and 100 µM) to the brain surface. TBI increased mNSS scores compared to baseline and confirmed mild TBI (mTBI) severity. CBF was significantly impaired on the ipsilateral side of the brain following mTBI, compared to contralateral side and to sham rats. SB dose-dependently improved CBF on the ipsilateral side after mTBI compared to SB effects on the respective ipsilateral side of sham rats but had no effect on contralateral CBF or in uninjured rats. N/OFQ levels increased in the cerebral spinal fluid (CSF) following mTBI, which correlated with the percent decrease in ipsilateral CBF. TBI also activated ERK and cofilin within 3 h post-TBI; ERK activation correlated with increased CSF N/OFQ. In conclusion, this study reveals a significant contribution of the N/OFQ-NOP receptor system to TBI-induced dysregulation of cerebral vasculature and suggests that the NOP receptor should be considered as a potential therapeutic target for TBI.

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Section: Discussionsupporting

confidence: 92%

The Nociceptin/Orphanin FQ peptide receptor antagonist, SB-612111, improves cerebral blood flow in a rat model of traumatic brain injury

Al Yacoub,

Tarantini,

Zhang

et al. 2023

Front. Pharmacol.

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“…Early and sub-acute elevations (2 h to 5 days) of UCH-L1 [47,48] and NF-L [49,50] levels were reported in serum and CSF post-TBI, with GFAP elevated as early as 3 days post-TBI [51,52], but we found no changes in tissue 3 h post-TBI [33] or at the 24 h time point in this study (Figure 5). However, a large, severity-dependent increase in the expression of GFAP and NF-L in ipsilateral tissue was found 8 days following CCI TBI in male and female rats [38].…”

Section: Discussioncontrasting

confidence: 50%

Traumatic Brain Injury Induces Nociceptin/Orphanin FQ and Nociceptin Opioid Peptide Receptor Expression within 24 Hours

Al Yacoub,

Zhang,

Patankar

et al. 2024

IJMS

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Traumatic brain injury (TBI) is a major cause of mortality and disability around the world, for which no treatment has been found. Nociceptin/Orphanin FQ (N/OFQ) and the nociceptin opioid peptide (NOP) receptor are rapidly increased in response to fluid percussion, stab injury, and controlled cortical impact (CCI) TBI. TBI-induced upregulation of N/OFQ contributes to cerebrovascular impairment, increased excitotoxicity, and neurobehavioral deficits. Our objective was to identify changes in N/OFQ and NOP receptor peptide, protein, and mRNA relative to the expression of injury markers and extracellular regulated kinase (ERK) 24 h following mild (mTBI) and moderate TBI (ModTBI) in wildtype (WT) and NOP receptor-knockout (KO) rats. N/OFQ was quantified by radioimmunoassay, mRNA expression was assessed using real-time PCR and protein levels were determined by immunoblot analysis. This study revealed increased N/OFQ mRNA and peptide levels in the CSF and ipsilateral tissue of WT, but not KO, rats 24 h post-TBI; NOP receptor mRNA increased after ModTBI. Cofilin-1 activation increased in the brain tissue of WT but not KO rats, ERK activation increased in all rats following ModTBI; no changes in injury marker levels were noted in brain tissue at this time. In conclusion, this study elucidates transcriptional and translational changes in the N/OFQ-NOP receptor system relative to TBI-induced neurological deficits and initiation of signaling cascades that support the investigation of the NOP receptor as a therapeutic target for TBI.

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“…27 Therefore, the expression levels of both IL-6 and TNF-α were tested owing to their roles as important inflammatory molecules in TBIs. 28,29 The results showed that a TBI significantly increased the expression levels of IL-6 and TNF-α (p < 0.01). Compared with the TBI group, TNS treatment alleviated the increase in IL-6 and TNF-α expression levels that were induced by the TBI (p < 0.01) (Fig.…”

Section: The Effects Of Tns On Inflammation and Apoptosismentioning

confidence: 98%

The Effectiveness of Trigeminal Nerve Stimulation on Traumatic Brain Injury

Yang

Zhang

et al. 2022

Neuromodulation: Technology at the Neural Interface

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<p>Antiapoptotic and Anti-Inflammatory Effects of CPCGI in Rats with Traumatic Brain Injury</p>

Cited by 8 publications

References 38 publications

The Nociceptin/Orphanin FQ peptide receptor antagonist, SB-612111, improves cerebral blood flow in a rat model of traumatic brain injury

The Nociceptin/Orphanin FQ peptide receptor antagonist, SB-612111, improves cerebral blood flow in a rat model of traumatic brain injury

Traumatic Brain Injury Induces Nociceptin/Orphanin FQ and Nociceptin Opioid Peptide Receptor Expression within 24 Hours

The Effectiveness of Trigeminal Nerve Stimulation on Traumatic Brain Injury

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