IRE1α inhibition decreased TXNIP/NLRP3 inflammasome activation through miR-17-5p after neonatal hypoxic-ischemic brain injury in rats.

Background: The endoplasmic reticulum (ER) is responsible for the control of correct protein folding and protein function which is crucial for cell survival. However, under pathological conditions, such as hypoxia-ischemia (HI), there is an accumulation of unfolded proteins thereby triggering the unfolded protein response (UPR) and causing ER stress which is associated with activation of several stress sensor signaling pathways, one of them being the inositol requiring enzyme-1 alpha (IRE1α) signaling pathway. The UPR is regarded as a potential contributor to neuronal cell death and inflammation after HI.

Targeting Germinal Matrix Hemorrhage-Induced Overexpression of Sodium-Coupled Bicarbonate Exchanger Reduces Posthemorrhagic Hydrocephalus Formation in Neonatal Rats.

Background: Germinal matrix hemorrhage (GMH) is a leading cause of mortality and lifelong morbidity in preterm infants. Posthemorrhagic hydrocephalus (PHH) is a common complication of GMH. A sodium-coupled bicarbonate exchanger (NCBE) encoded by solute carrier family 4 member 10 gene is expressed on the choroid plexus basolateral membrane and may play a role in cerebrospinal fluid production and the development of PHH.

Delayed Recanalization Promotes Functional Recovery in Rats Following Permanent Middle Cerebral Artery Occlusion.

Most large vessel stroke patients have permanent occlusion, for which there are no current treatment options. Recent case studies have indicated delayed recanalization, that is recanalization outside of the 6-h treatment window, may lead to improved outcome. We hypothesized that delayed recanalization will restore cerebral blood flow, leading to improved function in rats.

Epothilone B Benefits Nigrostriatal Pathway Recovery by Promoting Microtubule Stabilization After Intracerebral Hemorrhage.

Background: Many previous clinical studies have demonstrated that the nigrostriatal pathway, which plays a vital role in movement adjustment, is significantly impaired after stroke, according to medical imaging and autopsies. However, the basic pathomorphological changes have been poorly investigated to date. This study was designed to explore the pathomorphological changes, mechanism, and therapeutic method of nigrostriatal impairment after intracerebral hemorrhage (ICH).

Activation of dopamine D1 receptor decreased NLRP3-mediated inflammation in intracerebral hemorrhage mice.

Background: Inflammasomes are involved in diverse inflammatory diseases. Previous study reported that the neurotransmitter dopamine inhibited NLRP3 inflammasome activation via dopamine D1 receptor (DRD1). The present study aims to investigate the role of DRD1 on neuroinflammation in intracerebral hemorrhage (ICH) mice and the potential mechanism mediated by NLRP3 inhibition.

CpG-ODN exerts a neuroprotective effect via the TLR9/pAMPK signaling pathway by activation of autophagy in a neonatal HIE rat model.

Hypoxic Ischemic Encephalopathy (HIE) is an injury caused to the brain due to prolonged lack of oxygen and blood supply which results in death or long-term disabilities. The main aim of this study was to investigate the role of Cytosine-phospho-guanine oligodeoxynucleotide (CpG-ODN) in autophagy after HIE. Ten-day old (P10) rat pups underwent right common carotid artery ligation followed by 2.

Dihydrolipoic Acid Inhibits Lysosomal Rupture and NLRP3 Through Lysosome-Associated Membrane Protein-1/Calcium/Calmodulin-Dependent Protein Kinase II/TAK1 Pathways After Subarachnoid Hemorrhage in Rat.

Background And Purpose: The NLRP3 (nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3) inflammasome is a crucial component of the inflammatory response in early brain injury after subarachnoid hemorrhage (SAH). In this study, we investigated a role of dihydrolipoic acid (DHLA) in lysosomal rupture, NLRP3 activation, and determined the underlying pathway.

Methods: SAH was induced by endovascular perforation in male Sprague-Dawley rats.

Therapeutic effect of molecular hydrogen in corneal UVB-induced oxidative stress and corneal photodamage.

The aim of this study is to examine whether molecular hydrogen (H) is able to reduce oxidative stress after corneal damage induced by UVB irradiation. We previously found that UVB irradiation of the cornea caused the imbalance between the antioxidant and prooxidant enzymes in the corneal epithelium, followed by the imbalance between metalloproteinases and their physiological inhibitors (imbalances in favour of prooxidants and metalloproteinases) contributing to oxidative stress and development of the intracorneal inflammation. Here we investigate the effect of H dissolved in PBS in the concentration 0.

Bliverdin reductase-A improves neurological function in a germinal matrix hemorrhage rat model.

Germinal matrix hemorrhage is induced by stereotaxic injection of collagenase into the germinal matrix of P7 Sprague-Dawley rats. Hemoglobin assay, western blot, immunofluorescence and neurobehavioral tests were used to test the effects of BLVRA on hematoma resolution and anti-inflammatory response. We showed that BLVRA triggered a signaling cascade that ameliorated post-hemorrhagic neurological deficits in both short-term and long-term neurobehavioral tests in a GMH rat model.

A Look into Stem Cell Therapy: Exploring the Options for Treatment of Ischemic Stroke.

Neural stem cells (NSCs) offer a potential therapeutic benefit in the recovery from ischemic stroke. Understanding the role of endogenous neural stem and progenitor cells under normal physiological conditions aids in analyzing their effects after ischemic injury, including their impact on functional recovery and neurogenesis at the site of injury. Recent animal studies have utilized unique subsets of exogenous and endogenous stem cells as well as preconditioning with pharmacologic agents to better understand the best situation for stem cell proliferation, migration, and differentiation.

Cerebral venous collaterals: A new fort for fighting ischemic stroke?

Stroke therapy has entered a new era highlighted by the use of endovascular therapy in addition to intravenous thrombolysis. However, the efficacy of current therapeutic regimens might be reduced by their associated adverse events. For example, over-reperfusion and futile recanalization may lead to large infarct, brain swelling, hemorrhagic complication and neurological deterioration.

Axl activation attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after MCAO in rats.

Background And Purpose: Ischemic stroke activates Toll-like receptors (TLRs), triggering rapid inflammatory cytokine production. Axl signaling has multiple roles, including regulating cytokine secretion, clearing apoptotic cells, and maintaining cell survival, however, its role in inflammation after ischemic stroke has not been examined. We hypothesized that activation of Axl by recombinant Growth-arrest-specific protein 6 (rGas6) attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after middle cerebral artery occlusion (MCAO) in rats.

Recombinant Netrin-1 binding UNC5B receptor attenuates neuroinflammation and brain injury via PPARγ/NFκB signaling pathway after subarachnoid hemorrhage in rats.

Neuroinflammation is an essential mechanism involved in the pathogenesis of subarachnoid hemorrhage (SAH)-induced brain injury. Recently, Netrin-1 (NTN-1) is well established to exert anti-inflammatory property in non-nervous system diseases through inhibiting infiltration of neutrophil. The present study was designed to investigate the effects of NTN-1 on neuroinflammation, and the potential mechanism in a rat model of SAH.

Up-regulation of Wnt/β-catenin expression is accompanied with vascular repair after traumatic brain injury.

Recent data suggest that repairing the cerebral vasculature after traumatic brain injury (TBI) may help to improve functional recovery. The Wnt/β-catenin signaling pathway promotes blood vessel formation during vascular development, but its role in vascular repair after TBI remains elusive. In this study, we examined how the cerebral vasculature responds to TBI and the role of Wnt/β-catenin signaling in vascular repair.

IVIG activates FcγRIIB-SHIP1-PIP3 Pathway to stabilize mast cells and suppress inflammation after ICH in mice.

Following intracerebral hemorrhage (ICH), the activation of mast cell contributes to brain inflammation and brain injury. The mast cell activation is negatively regulated by an inhibitory IgG-receptor. It's signals are mediated by SHIP (Src homology 2-containing inositol 5' phosphatase), in particular SHIP1, which activation leads to hydrolyzation of PIP3 (Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P, leading to the inhibition of calcium mobilization and to the attenuation of mast cell activation.

Circular RNA DLGAP4 Ameliorates Ischemic Stroke Outcomes by Targeting miR-143 to Regulate Endothelial-Mesenchymal Transition Associated with Blood-Brain Barrier Integrity.

Circular RNAs (circRNAs) are highly expressed in the CNS and regulate physiological and pathophysiological processes. However, the potential role of circRNAs in stroke remains largely unknown. Here, we show that the circRNA DLGAP4 (circDLGAP4) functions as an endogenous microRNA-143 (miR-143) sponge to inhibit miR-143 activity, resulting in the inhibition of homologous to the E6-AP C-terminal domain E3 ubiquitin protein ligase 1 expression.

The Role of Thromboinflammation in Delayed Cerebral Ischemia after Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) is a major determinant of patient outcome following aneurysmal subarachnoid hemorrhage. Although the exact mechanisms leading to DCI are not fully known, inflammation, cerebral vasospasm, and microthrombi may all function together to mediate the onset of DCI. Indeed, inflammation is tightly linked with activation of coagulation and microthrombi formation.

Multiple mechanisms underlying neuroprotection by secretory phospholipase A2 preconditioning in a surgically induced brain injury rat model.

Background: Intra-operative bleeding, post-operative brain edema and neuroinflammation are major complications in patients with surgical brain injury (SBI). Phospholipase A2 (PLA2) is the upstream enzyme which initiates the PLA2, 5-lipoxygenase (5-LOX) and leukotriene B4 (LTB4) inflammatory pathway. We hypothesized PLA2preconditioning (PPC) prior to SBI can activate endogenous anti-inflammatory responses to protect against SBI.

Adropin preserves the blood-brain barrier through a Notch1/Hes1 pathway after intracerebral hemorrhage in mice.

Adropin is expressed in the CNS and plays a crucial role in the development of stroke. However, little is currently known about the effects of adropin on the blood-brain barrier (BBB) function after intracerebral hemorrhage (ICH). In this study, the role of adropin in collagenase-induced ICH was investigated in mice.

Bosutinib Attenuates Inflammation via Inhibiting Salt-Inducible Kinases in Experimental Model of Intracerebral Hemorrhage on Mice.

Background And Purpose: Intracerebral hemorrhage (ICH) is a subtype of stroke with highest mortality and morbidity. Pronounced inflammation plays a significant role in the development of the secondary brain injury after ICH. Recently, SIK-2 (salt-inducible kinase-2) was identified as an important component controlling inflammatory response.

Exendin-4 attenuates neuronal death via GLP-1R/PI3K/Akt pathway in early brain injury after subarachnoid hemorrhage in rats.

Neuronal apoptosis is considered to be a crucial therapeutic target against early brain injury (EBI) after subarachnoid hemorrhage (SAH). Emerging evidence indicates that Exendin-4 (Ex-4), a glucagon-like peptide 1 receptor (GLP-1R) agonist, plays a neuroprotective role in cerebrovascular disease. This study was conducted in order to verify the neuroprotective role of EX-4 in EBI after SAH in rats.

Recanalization, reperfusion, and recirculation in stroke.

Recirculation, from arterial inflow routes through venous outflow pathways, was conceptualized in stroke research 50 years ago. As new technologies were developed, blocked arteries could be reopened, capillaries could be reperfused, and the use of recanalization and reperfusion grew to dominate therapeutic strategies. These approaches overwhelmingly focused on restoration of arterial and capillary inflow, but not on veins even though venous disorders may initiate or exacerbate brain injury.

Traumatic Brain Injury and Stem Cell: Pathophysiology and Update on Recent Treatment Modalities.

Traumatic brain injury (TBI) is a complex condition that presents with a wide spectrum of clinical symptoms caused by an initial insult to the brain through an external mechanical force to the skull. In the United States alone, TBI accounts for more than 50,000 deaths per year and is one of the leading causes of mortality among young adults in the developed world. Pathophysiology of TBI is complex and consists of acute and delayed injury.