Global cerebral ischemia arises in patients who have a variety of clinical conditions including cardiac arrest, shock and asphyxia. In spite of advances in understanding of the brain ischemia and stroke etiology, therapeutic approaches to improve ischemic injury still remain limited. It has been established that metformin can attenuate cell death in cerebral ischemia. One of the main functions of metformin is proposed to be conducted via AMP-activated protein kinase (AMPK)-dependent pathway in the experimental cerebral ischemia model. It is also established that metformin can suppress inflammation and activate Nuclear factor erythroid 2-related factor (Nrf2) pathways in neurons. In the current study, the role of metformin in regulating inflammatory and antioxidant pathways in the global cerebral ischemia was investigated. Our results indicated that pretreatment of rats by metformin attenuated cellular levels of nuclear factor-κB, Tumor Necrosis Factor alpha and Cyclooxygenase-2 which are considered as three important proteins involved in the inflammation pathway. Pretreatment by metformin increased the level of Nrf2 and heme oxygenase-1 in the hippocampus of ischemic rats compared with untreated ischemic group. Moreover, pretreatment by metformin enhanced the level of glutathione and catalase activities compared with them in ischemic group. Such protective changes detected by metformin pretreatment were reversed by injecting compound c, an AMPK inhibitor. These findings suggested that metformin might protect cells through modulating inflammatory and antioxidant pathways via induction of AMPK. However, more experimental and clinical trial studies regarding neuroprotective potential of metformin and the involved mechanisms, especially in the context of cerebral ischemic injuries, are necessary.

No abstract

Inflammation is a devastating pathophysiological process during stroke, a devastating disease that is the second most common cause of death worldwide. Activation of the NOD-like receptor protein (NLRP3)-infammasome has been proposed to mediate inflammatory responses during ischemic stroke. Briefly, NLRP3 inflammasome activates caspase-1, which cleaves both pro-IL-1 and pro-IL-18 into their active pro-inflammatory cytokines that are released into the extracellular environment. Several NLRP3 inflammasome inhibitors have been promoted, including small molecules, type I interferon, micro RNAs, nitric oxide, and nuclear factor erythroid-2 related factor 2 (Nrf2), some of which are potentially efficacious clinically. This review will describe the structure and cellular signaling pathways of the NLRP3 inflammasome during ischemic stroke, and current evidence for NLRP3 inflammasome inhibitors.

No abstract

Following a traumatic brain injury (TBI), excessive release of proinflammatory cytokines is the major cause of cerebral edema and neuronal loss. This study was designed to examine changes in concentrations of some proinflammatory cytokines-including interleukin-1 beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta (TGF-β)-in a rat model of TBI in which the animals were treated with different doses of estrogen or progesterone 6 and 24 h after the TBI. Adult female rats were divided into 14 groups. Hormones or vehicle were given intraperitoneally 30 min after a moderate TBI was induced by the Marmarou method. The levels of proinflammatory cytokines in brain were measured at 6 and 24 h after the TBI. A high dose of estrogen (E2) or a low dose of progesterone (P1) increased brain levels of IL-1β 52.7% and 79.2% respectively at 6 h after the TBI. By 24h, IL-1β levels in the brain were 27.5% and 27% lower following administration of estrogen low dose (E1) or E2, respectively. High-dose administration of progesterone reduced brain levels of IL-6 to 45.9% at 6 h after the TBI, and P1 and E1 treatment significantly decreased IL-6 levels at 24 h. Brain levels of TNF-α were 72.5% lower at 6 h after the TBI following P2 treatment and 48.5% higher at 24 hrs following treatment with E2. The levels of TGF-β were also 3.37 times higher 24 h after the TBI following treatment with E1. Both doses of the hormones tested increases TGF-β levels 6 h after the TBI. Based on our findings, we conclude that progesterone and estrogen influence the levels of proinflammatory cytokines either at the primary or secondary stages after a TBI. Accordingly, this study suggests a mechanism by which hormones reduce cerebral edema.

No abstract

No abstract

No abstract