What are the progesterone-induced changes of the outcome and the serum markers of injury, oxidant activity and inflammation in diffuse axonal injury patients?

Abstract

To permit appropriate targeted therapy, the present clinical study was aimed to investigate the effects of progesterone on the outcome and the serum markers of injury, oxidant activity and inflammation in diffuse axonal injury (DAI). Forty-eight male DAI patients were divided into two groups (control and progesterone). Progesterone group received progesterone in dose of 1mg/kg per 12h for five days. The outcome was investigated using Extended Glasgow Outcome Scale (GOS-E) and functional independence measure (FIM). The markers of inflammation [interleukin-1β (IL-1β), IL-6, transforming growth factor-β1 (TGF-β1)], injury (brain protein of S-100B), and oxidant activity [malondialdehyde (MDA)] were evaluated in the serum of the patients. Higher GOS-E and FIM scores were observed in progesterone group at the six-month follow-up (P<0.05 and P<0.01, respectively). Meanwhile, a reduction in the serum levels of IL-1β, MDA and S-100B was noticed in progesterone group 24h after injury (P<0.05, P<0.001 and P<0.05, respectively), and there was an increase in serum levels of IL-6 and TGF-β1 (P<0.01 and P<0.05, respectively). Also, lower levels of MDA and S-100B, and higher levels of TGF-β1 were observed in progesterone group six days after injury (P<0.05). According to these findings, progesterone may improve the outcome in DAI patients probably through modulation in the levels of cytokines, and reduction in the injury and oxidant activity.

Evaluating the neurotherapeutic potential of a water-soluble progesterone analog after traumatic brain injury in rats

“…Three small, single-center clinical studies have now shown positive outcomes with low-dose i.m. PROG (Xiao et al, 2008;Mofid et al, 2016;Raheja et al, 2016), but large phase III clinical trials using i.v. administration at much higher doses of the hormone had negative results (Wright et al, 2007(Wright et al, , 2014Skolnick et al, 2014).…”

“…Further, three small, single-center clinical studies using lowdose intramuscular (i.m.) PROG have shown positive outcomes (Xiao et al, 2008;Mofid et al, 2016;Raheja et al, 2016). HBC has been used clinically (Preskorn, 2005;Mermelstein et al, 2013) as a vehicle for i.m.…”

Neuroprotective effect of berberine against learning and memory deficits in diffuse axonal injury

“…It has been proven that, after cerebral lesion, the concentrations of plasma TNF-α, IL-6 in DAI and IL-1β are increased (14). Meanwhile, encephal edema, hyperglycemia and subarachnoid hemorrhage further aggravate DAI and destroy the BBB.…”

The Serum Changes of Neuron-Specific Enolase and Intercellular Adhesion Molecule-1 in Patients With Diffuse Axonal Injury Following Progesterone Administration: A Randomized Clinical Trial

“…This study was part of a single- center blinded, randomized, controlled phase II trial of progesterone that a part of the results of trial has been published (19). The approval of the trial protocol was obtained from the ethics committee of Kerman University of Medical Sciences (K/92/579) prior to the commencement of the trial.…”

“…Also, the serum level of malondialdehyde (MDA), as an indication of lipid peroxidation was reduced in them (19). However, the neuroprotective effect of progesterone on serum levels of NSE and ICAM-1 has not been investigated in clinical trial.…”