Progesterone Attenuates Brain Inflammatory Response and Inflammation-Induced Increase in Immature Myeloid Cells in a Mouse Model

Gutzeit, Ola; Segal, Linoy; Korin, Ben; Iluz, Roee; Khatib, Nizar; Dabbah-Assadi, Fadwa; Ginsberg, Yuval; Fainaru, Ofer; Ross, Michael G.; Weiner, Zeev; Beloosesky, Ron

doi:10.1007/s10753-020-01390-y

Cited by 11 publications

(6 citation statements)

References 29 publications

(23 reference statements)

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“…P4 reduces brain edema (He et al., 2014 ) and retains BBB integrity (Si et al., 2014 ). It also decreases inflammatory response (Gutzeit et al., 2021 ) and pro‐inflammatory cytokines, including interleukin‐6 (IL‐6) (Sara et al., 2020 ), and transforming growth factor‐β (Khaksari et al., 2011 ; Sarkaki et al., 2011 ). Moreover, P4 suppresses oxidative stress and reduces cellular necrosis and apoptosis (Stanojlović et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Evaluating the neuroprotective effects of progesterone receptors on experimental traumatic brain injury: The PI3K/Akt pathway

Amirkhosravi,

khaksari,

Amiresmaili

et al. 2023

Brain and Behavior

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BackgroundStudies have confirmed the salutary effects of progesterone (P4) on traumatic brain injury (TBI). This study investigated the beneficial effects of P4 via its receptors on TBI, and also whether progesterone receptors (PRs) can modulate TBI through PI3K/Akt pathway.Material and methodsMarmarou method was utilized to induce diffuse TBI in ovariectomized rats. P4 (1.7 mg/kg) or the vehicle (oil) was administered 30 min after TBI induction. Moreover, RU486 (PR antagonist) and its vehicle (DMSO) were injected before TBI induction and P4 injection. Brain Evans blue content, brain water content (WC), various oxidative stress parameters, IL‐1β levels, tumor necrosis factor‐α (TNF‐α), histopathological alterations, and also phosphorylated Akt (p‐Akt) and PI3K expressions in the brain were assessed 24 h after TBI. The veterinary comma scale (VCS) was measured before and after TBI at different times.ResultsThe findings revealed that P4 caused an increase in VCS and a decrease in brain WC, oxidative stress, TNF‐α and IL‐1β levels. RU486 inhibited the beneficial effects of P4 on these indices. Moreover, RU486 prevented the reduction of brain edema, inflammation, and apoptosis caused by P4. Moreover, P4 following TBI increased the expression of PI3K/p‐Akt protein in the brain. RU486 eliminated the effects of P4 on PI3K/p‐Akt expression.ConclusionAccording to these findings, PRs are acting as critical mediators for the neuroprotective properties of P4 on oxidative stress, pro‐inflammatory cytokine levels, and neurological outcomes. PRs also play an important role in regulating the PI3K/p‐Akt expression and nongenomic function of P4.

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Section: Introductionmentioning

confidence: 99%

Evaluating the neuroprotective effects of progesterone receptors on experimental traumatic brain injury: The PI3K/Akt pathway

Amirkhosravi,

khaksari,

Amiresmaili

et al. 2023

Brain and Behavior

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“…Sex hormones have been extensively investigated for regulating microglia activation in various conditions. For example, progesterone attenuates brain inflammatory responses in rodent models [65]. Gonadal hormones differentially regulate sex-specific stress effects on glia in the medial prefrontal cortex [66].…”

Section: Discussionmentioning

confidence: 99%

Cocaine Regulates NLRP3 Inflammasome Activity and CRF Signaling in a Region- and Sex-Dependent Manner in Rat Brain

et al. 2023

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Cocaine, one of the most abused drugs worldwide, is capable of activating microglia in vitro and in vivo. Several neuroimmune pathways have been suggested to play roles in cocaine-mediated microglial activation. Previous work showed that cocaine activates microglia in a region-specific manner in the brains of self-administered mice. To further characterize the effects of cocaine on microglia and neuroimmune signaling in vivo, we utilized the brains from both sexes of outbred rats with cocaine self-administration to explore the activation status of microglia, NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activity, corticotropin-releasing factor (CRF) signaling, and NF-κB levels in the striatum and hippocampus (HP). Age-matched rats of the same sex (drug naïve) served as controls. Our results showed that cocaine increased neuroinflammation in the striatum and HP of both sexes with a relatively higher increases in male brains. In the striatum, cocaine upregulated NLRP3 inflammasome activity and CRF levels in males but not in females. In contrast, cocaine increased NLRP3 inflammasome activity in the HP of females but not in males, and no effects on CRF signaling were observed in this region of either sex. Interestingly, cocaine increased NF-κB levels in the striatum and HP with no sex difference. Taken together, our results provide evidence that cocaine can exert region- and sex-specific differences in neuroimmune signaling in the brain. Targeting neuroimmune signaling has been suggested as possible treatment for cocaine use disorders (CUDs). Our current results indicate that sex should be taken into consideration when determining the efficacy of these new therapeutic approaches.

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“…17-OHPC was reported to modestly prolong gestation in pregnant mice after inducing inflammation by LPS [25]. Further, progesterone and 17-OHPC improved neuronal function by inhibiting inflammation in animals [24,26,27]. The Anti-inflammatory role of 17-OHPC is further evidenced by the ability of 17-OHPC to attenuate the number of inflammatory cytokines in pregnant women.…”

Section: Immune Effects Of 17-ohpc and Its Implication In Preterm Lab...mentioning

confidence: 98%

17-α Hydroxyprogesterone Caproate Immunology, a Special Focus on Preterm Labor, Preeclampsia, and COVID-19

Al-Lami¹

2022

Reprod. Med.

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17-a hydroxyprogesterone caproate (17-OHPC) could alter the immune response and inflammation, specifically affecting the risk of preterm labor and preeclampsia. However, the exact immune and inflammatory effects of 17-OHPC remain hard to be identified. The current literature on 17-OHPC immune effects is limited and more research is needed to identify these mechanistic pathways. Further, coronavirus disease 2019 (COVID-19) infection in pregnancy involves heightened immune response, widespread inflammation and high rates of preterm labor and preeclampsia. Since the pathogenesis of preterm labor, preeclampsia and COVID-19 involves inflammation and altered immune response, it is important to explore the possible immune effects of 17-OHPC in pregnant women with COVID-19. This commentary article will explain the immune effects of 17-OHPC and their implications in preterm labor, preeclampsia and COVID-19.

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Progesterone Attenuates Brain Inflammatory Response and Inflammation-Induced Increase in Immature Myeloid Cells in a Mouse Model

Cited by 11 publications

References 29 publications

Evaluating the neuroprotective effects of progesterone receptors on experimental traumatic brain injury: The PI3K/Akt pathway

Evaluating the neuroprotective effects of progesterone receptors on experimental traumatic brain injury: The PI3K/Akt pathway

Cocaine Regulates NLRP3 Inflammasome Activity and CRF Signaling in a Region- and Sex-Dependent Manner in Rat Brain

17-α Hydroxyprogesterone Caproate Immunology, a Special Focus on Preterm Labor, Preeclampsia, and COVID-19

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