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

Abstract

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.

Progesterone induces neuroprotection associated with immune/inflammatory modulation in experimental traumatic brain injury

“…The cognitive deficits induced by TBI are an important cause of disability in patients [21]. Progesterone administration was shown to improve spatial memory and neurobehavioral outcomes in ovariectomized rats with TBI [22]. Here, we also demonstrated that progesterone can significantly reduce the cognitive deficits observed in the MWM test.…”

Aloe vera Leaf Extract Reduced BBB Permeability and Improved Neurological Results after Traumatic Brain Injury: The Role of Oxidative Stress

“…A total of 70 male Wistar rats were randomly assigned to five groups: Sham group: Rats in this group underwent the surgical procedure for traumatic brain injury (TBI) without actual induction of TBI [ 28 , 29 ]. TBI group: In this group, the animals were administered anesthesia with ketamine and xylazine before undergoing traumatic brain injury [ 28 , 29 ]. Vehicle group (VEH): Rats were intraperitoneally (i.p.)…”

“…Sham group: Rats in this group underwent the surgical procedure for traumatic brain injury (TBI) without actual induction of TBI [ 28 , 29 ].…”

“…TBI group: In this group, the animals were administered anesthesia with ketamine and xylazine before undergoing traumatic brain injury [ 28 , 29 ].…”

“…In the model, rats are first deeply anesthetized using a ketamine (80 mg/kg)/xylazine (15 mg/kg) cocktail [ 28 ]. Then a midline scalp incision is made to expose the skull using aseptic surgical techniques including sterile instruments and gloves.…”