Ginkgolide B ameliorates NLRP3 inflammasome activation after hypoxic‐ischemic brain injury in the neonatal male rat

2018 ◽  
Vol 69 (1) ◽  
pp. 106-111 ◽  
Author(s):  
Aiming Chen ◽  
Yin Xu ◽  
Jun Yuan
Keyword(s):  
Brain Injury ◽  
Nlrp3 Inflammasome ◽  
Male Rat ◽  
Inflammasome Activation ◽  
Ischemic Brain Injury ◽  
Ginkgolide B ◽  
Ischemic Brain ◽  
Nlrp3 Inflammasome Activation ◽  
Hypoxic Ischemic Brain Injury

scholarly journals Progesterone Attenuates Stress-Induced NLRP3 Inflammasome Activation and Enhances Autophagy Following Ischemic Brain Injury

2020 ◽  
Vol 21 (11) ◽  
pp. 3740 ◽  
Author(s):  
Claudia Espinosa-Garcia ◽  
Fahim Atif ◽  
Seema Yousuf ◽  
Iqbal Sayeed ◽  
Gretchen N. Neigh ◽  
...  
Keyword(s):  
Brain Injury ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Global Ischemia ◽  
Inflammasome Activation ◽  
Ischemic Brain Injury ◽  
Primary Microglia ◽  
Ischemic Brain ◽  
Nlrp3 Inflammasome Activation ◽  
The Impact

NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome inhibition and autophagy induction attenuate inflammation and improve outcome in rodent models of cerebral ischemia. However, the impact of chronic stress on NLRP3 inflammasome and autophagic response to ischemia remains unknown. Progesterone (PROG), a neuroprotective steroid, shows promise in reducing excessive inflammation associated with poor outcome in ischemic brain injury patients with comorbid conditions, including elevated stress. Stress primes microglia, mainly by the release of alarmins such as high-mobility group box-1 (HMGB1). HMGB1 activates the NLRP3 inflammasome, resulting in pro-inflammatory interleukin (IL)-1β production. In experiment 1, adult male Sprague-Dawley rats were exposed to social defeat stress for 8 days and then subjected to global ischemia by the 4-vessel occlusion model, a clinically relevant brain injury associated with cardiac arrest. PROG was administered 2 and 6 h after occlusion and then daily for 7 days. Animals were killed at 7 or 14 days post-ischemia. Here, we show that stress and global ischemia exert a synergistic effect in HMGB1 release, resulting in exacerbation of NLRP3 inflammasome activation and autophagy impairment in the hippocampus of ischemic animals. In experiment 2, an in vitro inflammasome assay, primary microglia isolated from neonatal brain tissue, were primed with lipopolysaccharide (LPS) and stimulated with adenosine triphosphate (ATP), displaying impaired autophagy and increased IL-1β production. In experiment 3, hippocampal microglia isolated from stressed and unstressed animals, were stimulated ex vivo with LPS, exhibiting similar changes than primary microglia. Treatment with PROG reduced HMGB1 release and NLRP3 inflammasome activation, and enhanced autophagy in stressed and unstressed ischemic animals. Pre-treatment with an autophagy inhibitor blocked Progesterone’s (PROG’s) beneficial effects in microglia. Our data suggest that modulation of microglial priming is one of the molecular mechanisms by which PROG ameliorates ischemic brain injury under stressful conditions.

scholarly journals NLRP3 Inflammasome Activation Is Involved in LPA1-Mediated Brain Injury after Transient Focal Cerebral Ischemia

2020 ◽  
Vol 21 (22) ◽  
pp. 8595
Author(s):  
Chi-Ho Lee ◽  
Arjun Sapkota ◽  
Bhakta Prasad Gaire ◽  
Ji Woong Choi
Keyword(s):  
Brain Injury ◽  
Cerebral Ischemia ◽  
Nlrp3 Inflammasome ◽  
Calcium Binding ◽  
Focal Cerebral Ischemia ◽  
Inflammasome Activation ◽  
Ischemic Brain ◽  
Caspase 1 ◽  
Transient Focal Cerebral Ischemia ◽  
Nlrp3 Inflammasome Activation

Lysophosphatidic acid receptor 1 (LPA1) contributes to brain injury following transient focal cerebral ischemia. However, the mechanism remains unclear. Here, we investigated whether nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation might be an underlying mechanism involved in the pathogenesis of brain injury associated with LPA1 following ischemic challenge with transient middle cerebral artery occlusion (tMCAO). Suppressing LPA1 activity by its antagonist attenuated NLRP3 upregulation in the penumbra and ischemic core regions, particularly in ionized calcium-binding adapter molecule 1 (Iba1)-expressing cells like macrophages of mouse after tMCAO challenge. It also suppressed NLRP3 inflammasome activation, such as caspase-1 activation, interleukin 1β (IL-1β) maturation, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) speck formation, in a post-ischemic brain. The role of LPA1 in NLRP3 inflammasome activation was confirmed in vitro using lipopolysaccharide-primed bone marrow-derived macrophages, followed by LPA exposure. Suppressing LPA1 activity by either pharmacological antagonism or genetic knockdown attenuated NLRP3 upregulation, caspase-1 activation, IL-1β maturation, and IL-1β secretion in these cells. Furthermore, nuclear factor-κB (NF-κB), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 were found to be LPA1-dependent effector pathways in these cells. Collectively, results of the current study first demonstrate that LPA1 could contribute to ischemic brain injury by activating NLRP3 inflammasome with underlying effector mechanisms.

Trace Fear Conditioning Detects Hypoxic-Ischemic Brain Injury in Neonatal Mice

2011 ◽  
Vol 33 (3-4) ◽  
pp. 222-230 ◽  
Author(s):  
Katarina Järlestedt ◽  
Alison L. Atkins ◽  
Henrik Hagberg ◽  
Marcela Pekna ◽  
Carina Mallard
Keyword(s):  
Brain Injury ◽  
Fear Conditioning ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Neonatal Mice ◽  
Trace Fear Conditioning ◽  
Hypoxic Ischemic Brain Injury ◽  
Trace Fear

Minocycline: A neuroprotective agent for hypoxic-ischemic brain injury in the neonate?

2009 ◽  
Vol 87 (3) ◽  
pp. 599-608 ◽  
Author(s):  
Kathryn M. Buller ◽  
Michelle L. Carty ◽  
Hanna E. Reinebrant ◽  
Julie A. Wixey
Keyword(s):  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Neuroprotective Agent ◽  
Hypoxic Ischemic Brain Injury

Focal protein synthesis inhibition in a model of neonatal hypoxic-ischemic brain injury

1987 ◽  
Vol 95 (2) ◽  
pp. 277-289 ◽  
Author(s):  
Barney E. Dwyer ◽  
Robert N. Nishimura ◽  
Clydette L. Powell ◽  
Susan L. Mailheau
Keyword(s):  
Protein Synthesis ◽  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Protein Synthesis Inhibition ◽  
Ischemic Brain ◽  
Synthesis Inhibition ◽  
Hypoxic Ischemic Brain Injury
Sign in / Sign up

Export Citation Format

Share Document