scholarly journals Activation of TRESK background potassium channels by cloxyquin exerts protective effects against excitotoxic-induced brain injury and neuroinflammation in neonatal rats

2021 ◽  
Author(s):  
Mustafa Dilek ◽  
Yasemin Baranoglu Kilinc ◽  
Erkan Kilinc ◽  
Ibrahim Ethem Torun ◽  
Aslihan Saylan ◽  
...  
Keyword(s):  
Brain Injury ◽  
Mast Cells ◽  
Potassium Channels ◽  
Brain Injuries ◽  
Activin A ◽  
Cresyl Violet ◽  
Intracerebral Injection ◽  
Protective Effects ◽  
Neonatal Rats ◽  
Rat Pups

Abstract The excitotoxicity is a common pathological mechanism of perinatal brain injuries (PBI), however neuroinflammation resulting in PBI is both a cause and a consequence of excitotoxicity. TRESK background potassium channels are an important regulator of neuronal excitability. We therefore investigated effects of activation of TRESK channels by selective activator cloxyquin on excitotoxic-induced brain injury and neuroinflammation involving brain mast cells and inflammatory cytokines in neonatal rats. An excitotoxic model mimicking human perinatal brain lesions was established via intracerebral injection of the glutamatergic agonist ibotenate to into newborn rats. P5 rat pups were intraperitoneally pretreated with vehicle, three different doses of cloxyquin (0.2, 1 and 5 mg/kg), or NMDA receptor antagonist MK-801 (positive control) 30 minutes prior to intracerebral injection of 10 µg ibotenate. Rat pups were sacrificed one or five days after the injury. Coronal brain sections were stained with cresyl-violet for histopathological examinations, and with toluidine-blue for brain mast cells assessments. Concentrations of activin A, IL-1β, IL-6 and IL-10 in brain homogenates were measured using ELISA. Cloxyquin dose-dependently ameliorated ibotenate-induced impairments in the cortical and white matter, and suppressed ibotenate-induced activation and number of brain mast cells. Moreover, cloxyquin dose-dependently reduced concentrations of activin A, IL-1β and IL-6 in the brain tissue induced by ibotenate while it elevated IL-10 level. Our findings reveal for the first time that cloxyquin, a selective activator of TRESK channels, dose-dependently exerted protective effects against excitotoxic-induced neonatal brain injury and neuroinflammation. TRESK channels may be a promising new target for the treatment of PBIs.

scholarly journals Hydrogen Gas Attenuates Hypoxic-Ischemic Brain Injury via Regulation of the MAPK/HO-1/PGC-1a Pathway in Neonatal Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Peipei Wang ◽  
Mingyi Zhao ◽  
Zhiheng Chen ◽  
Guojiao Wu ◽  
Masayuki Fujino ◽  
...  
Keyword(s):  
Brain Injury ◽  
Protein Kinase ◽  
Pc12 Cells ◽  
Heme Oxygenase 1 ◽  
Ischemic Brain Injury ◽  
Protective Effects ◽  
Neonatal Rats ◽  
Ischemic Brain ◽  
Differentiated Pc12 Cells ◽  
Hypoxic Ischemic Brain Injury

Neonatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of death in neonates with no effective treatments. Recent advancements in hydrogen (H2) gas offer a promising therapeutic approach for ischemia reperfusion injury; however, the impact of this approach for HIE remains a subject of debate. We assessed the therapeutic effects of H2 gas on HIE and the underlying molecular mechanisms in a rat model of neonatal hypoxic-ischemic brain injury (HIBI). H2 inhalation significantly attenuated neuronal injury and effectively improved early neurological outcomes in neonatal HIBI rats as well as learning and memory in adults. This protective effect was associated with initiation time and duration of sustained H2 inhalation. Furthermore, H2 inhalation reduced the expression of Bcl-2-associated X protein (BAX) and caspase-3 while promoting the expression of Bcl-2, nuclear factor erythroid-2-related factor 2, and heme oxygenase-1 (HO-1). H2 activated extracellular signal-regulated kinase and c-Jun N-terminal protein kinase and dephosphorylated p38 mitogen-activated protein kinase (MAPK) in oxygen-glucose deprivation/reperfusion (OGD/R) nerve growth factor-differentiated PC12 cells. Inhibitors of MAPKs blocked H2-induced HO-1 expression. HO-1 small interfering RNA decreased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and sirtuin 1 (SIRT1) and reversed the protectivity of H2 against OGD/R-induced cell death. These findings suggest that H2 augments cellular antioxidant defense capacity through activation of MAPK signaling pathways, leading to HO-1 expression and subsequent upregulation of PGC-1α and SIRT-1 expression. Thus, upregulation protects NGF-differentiated PC12 cells from OGD/R-induced oxidative cytotoxicity. In conclusion, H2 inhalation exerted protective effects on neonatal rats with HIBI. Early initiation and prolonged H2 inhalation had better protective effects on HIBI. These effects of H2 may be related to antioxidant, antiapoptotic, and anti-inflammatory responses. HO-1 plays an important role in H2-mediated protection through the MAPK/HO-1/PGC-1α pathway. Our results support further assessment of H2 as a potential therapeutic for neurological conditions in which oxidative stress and apoptosis are implicated.

Protective Effects of Valproic Acid Against Hypoxic-Ischemic Brain Injury in Neonatal Rats

2005 ◽  
Vol 20 (7) ◽  
pp. 582-587 ◽  
Author(s):  
Nimet Kabakus ◽  
Ilknur Ay ◽  
Sabiha Aysun ◽  
Figen Söylemezoglu ◽  
Ayhan Özcan ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Protective Effects ◽  
Neonatal Rats ◽  
Ischemic Brain ◽  
Hypoxic Ischemic Brain Injury

scholarly journals Siji Antiviral Mixture Protects against CA16 Induced Brain Injury through Inhibiting PERK/STAT3/NF-κB Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-15
Author(s):  
Huimin Xiao ◽  
Rong Zhao ◽  
Yue He ◽  
Yang Liu ◽  
Qiaoyan He ◽  
...  
Keyword(s):  
Brain Injury ◽  
Er Stress ◽  
Inflammatory Reaction ◽  
Brain Injuries ◽  
Interaction Mechanism ◽  
Foot And Mouth Disease ◽  
Neurological Complications ◽  
Protective Effects ◽  
Chromatographic Peaks

Coxsackievirus 16 (CA16) causes hand, foot, and mouth disease (HFMD) in young children and infants, and it can lead to fatal neurological complications. This study investigated antiviral effects of Siji Antiviral Mixture (SAM) on CA16 in neonatal mice and the protective effects of SAM on CA16 induced brain injuries. Neonatal BALB/c mice and SH-SY5Y cells were used and injected with CA16 stains to study the efficacy. ELISA and Western blotting were used to measure the cytokines levels and proteins expression. Genes transduction was also used to verify interaction mechanism. As the results shown, SAM could reduce the clinical scores at the beginning and delay disease developmentin vivo. Treatment with SAM decreased the levels of LDH, CK-MB, caspase 3 and Bax, ER stress, and inflammatory reaction induced by CA16 infection. Further siRNA transfection results showed that CA16 induced ER stress and inflammatory reaction through PERK/STAT3/NF-κB signaling and the protective effects of SAM might be through inhibiting PERK/STAT3/NF-κB signaling. HPLC analysis showed fingerprint profiles of SAM had 42 chromatographic peaks. Collectively, our study highlighted distinct roles of SAM in inhibiting CA16 infection and brain injury. The molecular mechanism of SAM might be through inhibiting PERK/STAT3/NF-κB signaling.

MANAGEMENT OF MULTIPLE TRAUMATIC INTRACRANIAL HEMATOMAS

2020 ◽  
Vol 3 (1) ◽  
pp. 70-74
Author(s):  
Rustam Hazratkulov ◽  
Keyword(s):  
Traumatic Brain Injury ◽  
Surgical Treatment ◽  
Brain Injury ◽  
Hospital Stay ◽  
Treatment Outcomes ◽  
Brain Injuries ◽  
Traumatic Brain Injuries ◽  
Diagnostic Approach ◽  
Early Activation ◽  
Intracranial Hematomas

Multiple traumatic hematomas (MG) account for 0.74% of all traumatic brain injuries. A comprehensive diagnostic approach to multiple traumatic intracranial hematomas allows to establish a diagnosis in the early stages of traumatic brain injury and to determine treatment tactics. A differentiated approach to the choice of surgical treatment of multiple hematomas allows to achieve satisfactory results and treatment outcomes, which accordingly contributes to the early activation of the patient, a reduction in hospital stay, a decrease in mortality and disabilityin patients with traumatic brain injury

scholarly journals Pathologically Entangled: Brain trauma-evoked ROS imbalance disrupts Kir channel function in distant peripheral vessels

Function ◽  
2021 ◽  
Author(s):  
Nick Weir ◽  
Thomas A Longden
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Potassium Channels ◽  
Vascular Function ◽  
Inward Rectifier ◽  
Brain Trauma ◽  
Channel Function ◽  
Inward Rectifier Potassium Channels ◽  
Kir Channel

Abstract A Perspective on "Traumatic Brain Injury Impairs Systemic Vascular Function Through Disruption of Inward-Rectifier Potassium Channels"

Rapid Detection of Significant Traumatic Brain Injury Requiring Emergency Intervention

2020 ◽  
pp. 000313482097335
Author(s):  
Isaac W. Howley ◽  
Jonathan D. Bennett ◽  
Deborah M. Stein
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Injuries ◽  
Trauma Team ◽  
Altered Mental Status ◽  
Acute Care Surgery ◽  
Ct Scanner ◽  
Mickey Mouse ◽  
Clinically Significant ◽  
Care Surgery

Moderate and severe traumatic brain injuries (TBI) are a major cause of severe morbidity and mortality; rapid diagnosis and management allow secondary injury to be minimized. Traumatic brain injury is only one of many potential causes of altered mental status; head computed tomography (HCT) is used to definitively diagnose TBI. Despite its widespread use and obvious importance, interpretation of HCT images is rarely covered by formal didactics during general surgery or even acute care surgery training. The schema illustrated here may be applied in a rapid and reliable fashion to HCT images, expediting the diagnosis of clinically significant traumatic brain injury that warrants emergent medical and surgical therapies to reduce intracranial pressure. It consists of 7 normal anatomic structures (cerebrospinal fluid around the brain stem, open fourth ventricle, “baby’s butt,” “Mickey Mouse ears,” absence of midline shift, sulci and gyri, and gray-white differentiation). These 7 features can be seen even as the CT scanner obtains images, allowing the trauma team to expedite medical management of intracranial hypertension and pursue neurosurgical consultation prior to radiologic interpretation if the features are abnormal.

scholarly journals Reply to Comment on Tsai, Y.-C., et al. Association of Stress-Induced Hyperglycemia and Diabetic Hyperglycemia with Mortality in Patients with Traumatic Brain Injury: Analysis of a Propensity Score-Matched Population. Int. J. Environ. Res. Public Health 2020, 17, 4266

2021 ◽  
Vol 18 (5) ◽  
pp. 2531
Author(s):  
Yu-Chin Tsai ◽  
Shao-Chun Wu ◽  
Ting-Min Hsieh ◽  
Hang-Tsung Liu ◽  
Chun-Ying Huang ◽  
...  
Keyword(s):  
Public Health ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Propensity Score ◽  
Brain Injuries ◽  
Traumatic Brain Injuries ◽  
Injury Analysis

Thank you for Eduardo Mekitarian Filho’s appreciation of our work on the study of stress-induced hyperglycemia (SIH) and diabetic hyperglycemia (DH) in patients with traumatic brain injuries [...]

scholarly journals Umbilical cord blood therapy modulates neonatal hypoxic ischemic brain injury in both females and males

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tayla R. Penny ◽  
Yen Pham ◽  
Amy E. Sutherland ◽  
Joohyung Lee ◽  
Graham Jenkin ◽  
...  
Keyword(s):  
Brain Injury ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Significant Risk ◽  
Immunohistochemical Analysis ◽  
Significant Risk Factor ◽  
Tissue Loss ◽  
Artery Ligation ◽  
Rat Pups

AbstractPreclinical and clinical studies have shown that sex is a significant risk factor for perinatal morbidity and mortality, with males being more susceptible to neonatal hypoxic ischemic (HI) brain injury. No study has investigated sexual dimorphism in the efficacy of umbilical cord blood (UCB) cell therapy. HI injury was induced in postnatal day 10 (PND10) rat pups using the Rice-Vannucci method of carotid artery ligation. Pups received 3 doses of UCB cells (PND11, 13, 20) and underwent behavioural testing. On PND50, brains were collected for immunohistochemical analysis. Behavioural and neuropathological outcomes were assessed for sex differences. HI brain injury resulted in a significant decrease in brain weight and increase in tissue loss in females and males. Females and males also exhibited significant cell death, region-specific neuron loss and long-term behavioural deficits. Females had significantly smaller brains overall compared to males and males had significantly reduced neuron numbers in the cortex compared to females. UCB administration improved multiple aspects of neuropathology and functional outcomes in males and females. Females and males both exhibited injury following HI. This is the first preclinical evidence that UCB is an appropriate treatment for neonatal brain injury in both female and male neonates.

Sign in / Sign up

Export Citation Format

Share Document