Time-Window of Progesterone Neuroprotection After Stroke and Its Underlying Molecular Mechanisms

Cai, Wei; Sokabe, Masahiro; Chen, Ling

doi:10.5772/32182

Cited by 2 publications

(4 citation statements)

References 59 publications

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“…In addition, PI3K/Akt signaling pathway can be used by P4 to decrease inflammation and protect brain (Ishrat et al., 2012 ). Regarding the specific PI3K inhibitor “LY294002,” evidence has shown that ischemia‐induced brain damage can be prevented, and for that, P4 neuroprotection PI3K signaling is required (Cai et al., 2012 ). In a P4R‐dependent manner, P4 causes the immediate and temporary activation of PI3K‐Akt pathway (Migliaccio et al., 1998 ; Vallejo et al., 2005 ).…”

Section: Discussionmentioning

confidence: 99%

“…Evidence has demonstrated that the Src‐ERK signaling pathway is activated by P4R (Boonyaratanakornkit et al., 2008 ) by the phosphorylation of ERK1/2 (Cai et al., 2008 ). The membrane‐impermeant P4‐BSA, which interacts with the intracellular PR, elicits ERK phosphorylation (Cai et al., 2012 ; Jodhka et al., 2009 ). It has also been revealed that the neuroprotection effect mediated by PI3K is not dependent on P4R.…”

Section: Discussionmentioning

confidence: 99%

“…Besides, RU486 causes a rise in caspase‐3 activity and DNA fragmentation (Svensson et al., 2001 ). Additionally, RU486 removes P4's neuroprotective properties in ischemia‐induced neuronal death (Cai et al., 2012 ). Not assessing fluorescent staining for microglia proliferation markers and apoptosis is one of the limitations of this study.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the PI3K/p‐Akt pathway has a neuroprotective role after ischemic injury (Wang et al., 2009 ). Treatment with P4 significantly increases p‐Akt after ischemic stroke (Ishrat et al., 2012 ), and this signaling pathway is involved in the PR‐dependent neuroprotection through P4 (Cai et al., 2012 ).…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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The 5α-Reductase Inhibitor Finasteride Exerts Neuroprotection Against Ischemic Brain Injury in Aged Male Rats

Tanaka

Ogaeri

Samsonov

et al. 2018

Transl. Stroke Res.

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Progesterone (P4) exerts potent neuroprotection both in young and aged animal models of stroke. The neuroprotection is likely to be mediated by allopregnanolone (ALLO) metabolized from P4 by 5α-reductase, since the neuroprotection is attenuated by the 5α-reductase inhibitor finasteride, which was done only with young animals though. Thus, we do not know the contribution of ALLO to the P4-induced neuroprotection in aged animals. We examined effects of finasteride on the P4-induced neuroprotection in aged (16-18-month-old) male rats subjected to transient focal cerebral ischemia. Transient focal cerebral ischemia was induced by left middle cerebral artery occlusion (MCAO) and occlusion of the bilateral common carotid arteries. MCAO rats were given an 8 mg/kg P4 6 h after MCAO followed by the same treatment once a day for successive 3 days. Finasteride, a 5α-reductase inhibitor, at 20 mg/kg was intraperitoneally injected 30 min prior to the P4-injections. P4 markedly reduced neuronal damage 72 h after MCAO, and the P4-induced neuroprotection was apparently suppressed by finasteride in the aged animals. However, post-ischemic administration of finasteride alone (20 mg/kg) significantly prevented neuronal damage and the impairment of Rotarod performance after MCAO in aged male rats, but not in young ones. The androgen receptor antagonist flutamide markedly suppressed the neuroprotection of finasteride in the cerebral cortex, but not in the striatum, suggesting the androgen receptor-dependent mechanism of the finasteride-induced neuroprotection in the cerebral cortex. Our findings suggested, for the first time, the potential of finasteride as a therapeutic agent in post-ischemic treatment of strokes in aged population.

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Time-Window of Progesterone Neuroprotection After Stroke and Its Underlying Molecular Mechanisms

Cited by 2 publications

References 59 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

The 5α-Reductase Inhibitor Finasteride Exerts Neuroprotection Against Ischemic Brain Injury in Aged Male Rats

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