scholarly journals Activation of alpha-4 beta-2 nicotinic receptor against cardiopulmonary bypass surgery induced brain injury by regulating NLRP3 pathway

2020 ◽  
Author(s):  
Xiuye Liu ◽  
Lijuan Yang ◽  
Li Wang ◽  
Qionghai Guo
Keyword(s):  
Cardiopulmonary Bypass ◽  
Brain Injury ◽  
Brain Tissue ◽  
Nicotinic Receptor ◽  
Neuronal Apoptosis ◽  
Bypass Surgery ◽  
Treated Group ◽  
Brain Injured ◽  
Beta 2 ◽  
The Brain

Abstract Present report evaluates the role of alpha-4 beta-2 nicotinic receptor (α4β2 nAChRs) in the development of cardiopulmonary bypass (CPB) surgery induced brain injury. Brain injury was induced by CPB and animals were treated with α4β2 nAChRs agonist (DHβE 9 mg/kg, s.c.) and α4β2 nAChRs antagonist (MLA 10 mg/kg, i.p.) 3 hr before the induction of CPB in the separate groups. Effect of α4β2 nAChRs agonist was determined on the neurological function in CPB induced brain injured rats. Level of cytokines, ROS and expression of NLRP3, ZO-1 and Occluding proteins were estimated in CPB induced brain injured rats. Effect of α4β2 nAChRs agonist was determined on the neuronal apoptosis and histopathological changes in the brain tissue. Result of the study suggest that neurological score was reversed in α4β2 nAChRs agonist treated group than CPB group. Level of cytokines and ROS was reduced in α4β2 nAChRs agonist treated group than CPB group. Neuronal apoptosis in α4β2 nAChRs agonist treated group was found to be reduced compared to CPB group of rats. Moreover Activation of α4β2 nAChRs ameliorates the altered expression of NLRP3, ZO-1 and Occluding protein in the brain tissue of CPB induced brain injured rats. In conclusion, Data of report suggest that treatment with α4β2 nAChRs agonist protects the brain injury in cardiopulmonary bypass surgery induced brain injury by regulating NLRP3 pathway.

scholarly journals Effect of Xenon Treatment on Gene Expression in Brain Tissue after Traumatic Brain Injury in Rats

2021 ◽  
Vol 11 (7) ◽  
pp. 889
Author(s):  
Anton D. Filev ◽  
Denis N. Silachev ◽  
Ivan A. Ryzhkov ◽  
Konstantin N. Lapin ◽  
Anastasiya S. Babkina ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Tissue ◽  
Target Genes ◽  
Neural Function ◽  
Stress Genes ◽  
Expression Of Genes ◽  
Delayed Recovery ◽  
The Brain ◽  
Lower Expression

The overactivation of inflammatory pathways and/or a deficiency of neuroplasticity may result in the delayed recovery of neural function in traumatic brain injury (TBI). A promising approach to protecting the brain tissue in TBI is xenon (Xe) treatment. However, xenon’s mechanisms of action remain poorly clarified. In this study, the early-onset expression of 91 target genes was investigated in the damaged and in the contralateral brain areas (sensorimotor cortex region) 6 and 24 h after injury in a TBI rat model. The expression of genes involved in inflammation, oxidation, antioxidation, neurogenesis and neuroplasticity, apoptosis, DNA repair, autophagy, and mitophagy was assessed. The animals inhaled a gas mixture containing xenon and oxygen (ϕXe = 70%; ϕO2 25–30% 60 min) 15–30 min after TBI. The data showed that, in the contralateral area, xenon treatment induced the expression of stress genes (Irf1, Hmox1, S100A8, and S100A9). In the damaged area, a trend towards lower expression of the inflammatory gene Irf1 was observed. Thus, our results suggest that xenon exerts a mild stressor effect in healthy brain tissue and has a tendency to decrease the inflammation following damage, which might contribute to reducing the damage and activating the early compensatory processes in the brain post-TBI.

scholarly journals Sevoflurane Exacerbates Cognitive Impairment Induced by Aβ1–40 in Rats through Initiating Neurotoxicity, Neuroinflammation, and Neuronal Apoptosis in Rat Hippocampus

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yue Tian ◽  
Ke-yan Chen ◽  
Li-dan Liu ◽  
Yun-xia Dong ◽  
Ping Zhao ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Calcium Binding ◽  
Neuronal Apoptosis ◽  
Treated Group ◽  
Rat Hippocampus ◽  
Inos Mrna ◽  
Caspase 9 ◽  
Glycation End Products ◽  
Oxide Synthase ◽  
The Brain

Objective. This study was aimed at investigating whether sevoflurane inhalation induced cognitive impairment in rats with a possible mechanism involved in the event. Methods. Thirty-two rats were randomly divided into four groups of normal saline (NS) + O2, NS + sevoflurane (sevo), amyloid-β peptide (Aβ) + O2, and Aβ + sevo. The rats in the four groups received bilateral intrahippocampus injections of NS or Aβ. The treated hippocampus was harvested after inhaling 30% O2 or 2.5% sevoflurane. Evaluation of cognitive function was performed by Morris water maze (MWZ) and an Aβ1–42 level was determined by ELISA. Protein and mRNA expressions were executed by immunohistochemical (IHC) staining, Western blotting, and qRT-PCR. Results. Compared with the NS-treated group, sevoflurane only caused cognitive impairment and increased the level of Aβ1–42 of the brain in the Aβ-treated group. Sevoflurane inhalation but not O2 significantly increased glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule (IBA)1 expression in Aβ-treated hippocampus of rats. Expression levels for Bcl-xL, caspase-9, receptor for advanced glycation end products (RAGE) and brain-derived neurotrophic factor (BDNF) were significantly different in quantification of band intensity between the rats that inhaled O2 and sevoflurane in Aβ-treated groups (all P<0.05). Interleukin- (IL-) 1β, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) mRNA expression increased after the rats inhaled sevoflurane in the Aβ-treated group (both P<0.01). There were no significant differences in the change of GFAP, IBA1, Bcl-xL, caspase-9, RAGE, BDNF, IL-1β, NF-κB, and iNOS in the NS + O2 and NS + sevo group (all P>0.05). Conclusion. Sevoflurane exacerbates cognitive impairment induced by Aβ1–40 in rats through initiating neurotoxicity, neuroinflammation, and neuronal apoptosis in rat hippocampus.

scholarly journals Fangchinoline ameliorates the expressions of angiogenic molecule in cerebral ischemia induced neuronal degeneration in neonatal rats

2018 ◽  
Vol 9 (1) ◽  
pp. 117-122
Author(s):  
Han Daicheng ◽  
Xia Shiwen ◽  
Zhu Huaping ◽  
Liu Yong ◽  
Zhou Qianqian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Neuronal Degeneration ◽  
Neuronal Injury ◽  
Enzyme Linked Immunosorbent Assay ◽  
Neonatal Rats ◽  
Markers Of Oxidative Stress ◽  
The Brain

AbstractBackgroundPresent investigation evaluates the beneficial effect of fangchinoline on cerebral ischemia induced neuronal degeneration in neonatal rats and also postulates the possible mechanism of its action.MethodologyCerebral ischemia was produced by the ligation of right common carotid artery in neonatal rats on postnatal day 5 (P5) and further pups were treated with fangchinoline 3, 10 and 30 mg/kg, i.p. for the period of 3 days. Effect of fangchinoline was estimated by determining the brain injury and enzyme linked immunosorbent assay (ELISA) method was used for the estimation of pro-inflammatory mediators and markers of oxidative stress in the cerebral tissues of neonatal rats. Moreover western blot assay and histopathology study was also performed on the brain tissue.ResultsResult of this investigation reveals that the percentage of brain injury significantly reduces and enhancement of myelin basic protein in the cerebral tissues of fangchinoline than ischemic group. Treatment with fangchinoline attenuates the altered level of proinflammatory mediators and markers of oxidative stress in the cerebral tissue of cerebral ischemia induced neuronal injury neonatal rats. Moreover expressions of inducible nitric oxide synthtase (iNOS), vascular endothelial growth factor (VEGF), p53 and nuclear receptor factor-2 (Nrf2) in the brain tissue attenuated by fangchinoline treated group.ConclusionIn conclusion, fangchinoline ameliorates the cerebral ischemia induced neuronal injury in neonatal rats by enhancing angiogenesis molecules.

scholarly journals Inhibiting HMGB1 with Glycyrrhizic Acid Protects Brain Injury after DAI via Its Anti-Inflammatory Effect

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Honggang Pang ◽  
Tinqin Huang ◽  
Jinning Song ◽  
Dandong Li ◽  
Yonglin Zhao ◽  
...  
Keyword(s):  
Brain Injury ◽  
Inflammatory Response ◽  
Proinflammatory Cytokines ◽  
Neuronal Apoptosis ◽  
Glycyrrhizic Acid ◽  
Axonal Injury ◽  
Tunel Staining ◽  
Hmgb1 Level ◽  
Associated Proteins ◽  
The Brain

High-mobility group box 1 (HMGB1), a nuclear protein that has endogenous cytokine-like activity, is involved in several neurological diseases by mediating inflammatory response. In this study, a lateral head rotation device was used to establish a rat diffuse axonal injury (DAI) model. The dynamic expression of HMGB1, apoptosis-associated proteins, and proinflammatory cytokines were detected by Western blot, and neuronal apoptosis was observed by TUNEL staining. The extracellular release of HMGB1 and the accumulation ofβ-APP were observed by immunofluorescence and immunohistochemistry, respectively. The brain injury was indicated by modified neurological severity score (mNSS), brain water content (BWC), and the extravasation of Evans blue. We showed that HMGB1 level obviously decreased within 48 h after DAI, accompanied by neuronal apoptosis, the activation of caspases 3 and 9, and the phosphorylation of BCL-2. Inhibiting HMGB1 with glycyrrhizic acid (GL) can suppress the activation of apoptosis-associated proteins and inhibit the expression of proinflammatory cytokines, which ameliorated motor and cognitive deficits, reduced neuronal apoptosis, and protected the integrity of blood brain barrier (BBB) and axonal injury after experimental DAI in rats. Thus, HMGB1 may be involved in the inflammatory response after DAI, and inhibition of HMGB1 release with GL can notably alleviate the brain injury after DAI.

scholarly journals Residual Pituitary Function after Brain Injury-Induced Hypopituitarism: A Prospective 12-Month Study

2005 ◽  
Vol 90 (11) ◽  
pp. 6085-6092 ◽  
Author(s):  
Gianluca Aimaretti ◽  
Maria Rosaria Ambrosio ◽  
Carolina Di Somma ◽  
Maurizio Gasperi ◽  
Salvatore Cannavò ◽  
...  
Keyword(s):  
Brain Injury ◽  
High Risk ◽  
Gh Deficiency ◽  
Pituitary Function ◽  
Brain Injured ◽  
Injured Patients ◽  
The Brain ◽  
Over Time

Abstract Context: Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are conditions at high risk for the development of hypopituitarism. Objective: The objective of the study was to clarify whether pituitary deficiencies and normal pituitary function recorded at 3 months would improve or worsen at 12 months after the brain injury. Design and Patients: Pituitary function was tested at 3 and 12 months in patients who had TBI (n = 70) or SAH (n = 32). Results: In TBI, the 3-month evaluation had shown hypopituitarism (H) in 32.8%. Panhypopituitarism (PH), multiple (MH), and isolated (IH) hypopituitarism had been demonstrated in 5.7, 5.7, and 21.4%, respectively. The retesting demonstrated some degree of H in 22.7%. PH, MH, and IH were present in 5.7, 4.2, and 12.8%, respectively. PH was always confirmed at 12 months, whereas MH and IH were confirmed in 25% only. In 5.5% of TBI with no deficit at 3 months, IH was recorded at retesting. In 13.3% of TBI with IH at 3 months, MH was demonstrated at 12-month retesting. In SAH, the 3-month evaluation had shown H in 46.8%. MH and IH had been demonstrated in 6.2 and 40.6%, respectively. The retesting demonstrated H in 37.5%. MH and IH were present in 6.2 and 31.3%, respectively. Although no MH was confirmed at 12 months, two patients with IH at 3 months showed MH at retesting; 30.7% of SAH with IH at 3 months displayed normal pituitary function at retesting. In SAH, normal pituitary function was always confirmed. In TBI and SAH, the most common deficit was always severe GH deficiency. Conclusion: There is high risk for H in TBI and SAH patients. Early diagnosis of PH is always confirmed in the long term. Pituitary function in brain-injured patients may improve over time but, although rarely, may also worsen. Thus, brain-injured patients must undergo neuroendocrine follow-up over time.

Oral-Movement Abilities and Articulatory Characteristics of Brain-Injured Adults

1974 ◽  
Vol 39 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Leonard L. La Pointe ◽  
Robert T. Wertz
Keyword(s):  
Brain Injury ◽  
Apraxia Of Speech ◽  
Oral Motor ◽  
Brain Injured ◽  
History Of ◽  
Injured Patients ◽  
The Brain ◽  
Normal Adults

We compared the performance of 28 brain-injured adults who displayed articulation problems with that of 28 adults with no history of brain-injury on tests of isolated oral movement and oral-motor sequencing. An attempt was made to classify the brain-injured patients by administering an articulation test and employing three criteria for differentiating apraxia of speech from dysarthria: presence of initiation errors, more substitution errors than combined omission and distortion errors, and the presence of islands of error-free production. While the brain-injured group performed significantly worse on the isolated oral-movement and oral-motor sequencing tests than the normal adults, not all brain-injured patients demonstrated difficulty on these tasks. We were able to identify 13 patients who met all three criteria (apraxia of speech), 3 who met none (dysarthria), and 12 who met one or two but not all (mixed apraxia of speech and dysarthria). Isolated oral-movement and oral-motor sequencing deficits were found in all three groups, but no significant differences among groups on these tasks were observed.

scholarly journals κ-Opioid Receptor Agonist Ameliorates Postoperative Neurocognitive Disorder by Activating the Ca2+/CaMKII/CREB Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Guopeng Ding ◽  
Dandan Li ◽  
Yingjie Sun ◽  
Keyan Chen ◽  
Dandan Song
Keyword(s):  
Oxidative Stress ◽  
Cardiopulmonary Bypass ◽  
Brain Injury ◽  
Opioid Receptor ◽  
Stress Factors ◽  
Neurocognitive Disorder ◽  
Apoptosis Rate ◽  
The Brain ◽  
And Oxidative Stress ◽  
Creb Pathway

Objective. Cardiopulmonary bypass (CPB) is an important cardiac operation and also a high-risk procedure, leading to postoperative neurocognitive disorder. However, there are few effective drugs to treat the aftermath of CPB. Therefore, we observe the effect of kappa opioid receptor (KOR) agonist on cognitive disorders of rats after cardiopulmonary bypass (CPB) and investigate the mechanism of the Ca2+/calmodulin-dependent protein kinase (CaMKII)/cAMP responsive element-binding protein (CREB) pathway. Methods. A total of 40 Sprague Dawley rats were randomly divided into the sham operation group (sham group, n = 10), CPB model group (CPB group, n = 10), CPB + KOR agonist U50488H group (UH group, n = 10), and CPB + specific CaMKII antagonist + U50488H group (CKU group, n = 10). The changes in the rats’ cognitive function were evaluated using the Morris water maze, the hippocampal histopathological changes were observed via hematoxylin-eosin (H&E) staining, and the apoptosis rate of neuronal cells was detected through terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. Moreover, enzyme-linked immunosorbent assay (ELISA) was applied to examine the changes in brain injury markers, inflammatory factors, and oxidative stress factors. The hippocampal variations in Ca2+ concentration and oxidative stress index (ROS) levels were measured by immunofluorescence staining, and western blotting was performed to determine the expression changes in the Ca2+/CaMKII/CREB pathway. Results. The KOR agonist could shorten latency, increase the swimming distance and residence time in the target quadrant, and ameliorate postoperative neurocognitive disorder (PND). Meanwhile, the KOR agonist relieved CPB-induced hippocampal and oxidative stress injuries, reduced NSE and S-100β expression, decreased the apoptosis rate, and repressed the inflammatory response, which alleviated the brain injury. In addition, U50488H was able to decrease Ca2+ influx and glutamate (Glu) level, inhibit N-methyl-D-aspartate receptor (NMDAR) expression, upregulate CaMKII expression, promote CREB phosphorylation, and increase the brain-derived neurotrophic factor (BDNF) level in CPB rats. However, the protective effects of KORs against PND were suppressed following the application of the CaMKII-specific antagonist. Conclusion. The KOR agonist activates the Ca2+/CaMKII/CREB pathway, which improves the brain injury and relieves PND in CPB rats.

scholarly journals NEUROSONOGRAPHIC STUDY OF CHILDREN WITH HYPOXIC-ISCHEMIC BRAIN IJURY

2020 ◽  
pp. 7-11
Author(s):  
Volotko L. O.
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Injury ◽  
Brain Tissue ◽  
Ischemic Injury ◽  
Ischemic Brain ◽  
Destructive Processes ◽  
The Brain ◽  
Hypoxic Ischemic Injury

The study is aimed at neurosonographic characteristics of brain injury in newborn patients with perinatal hypoxic-ischemic injury of central nervous system, complicated with inflectional process (meningitis, ventriculitis). It is settled that brain immaturity, hydrocephalic syndrome, ischemia of the brain tissue and intraventricular hemorrhages are found 2 times more often in infants with perinatal hypoxic-ischemic injury of central nervous system, complicated with inflectional process. This fact generally characterizes disorders of the hemato-encephalic barrier and the development of destructive processes in the tissue of the brain.

scholarly journals Does Blast Exposure to the Torso Cause a Blood Surge to the Brain?

2020 ◽  
Vol 8 ◽  
Author(s):  
Jose E. Rubio ◽  
Maciej Skotak ◽  
Eren Alay ◽  
Aravind Sundaramurthy ◽  
Dhananjay Radhakrishnan Subramaniam ◽  
...  
Keyword(s):  
Brain Injury ◽  
Carotid Artery ◽  
Brain Tissue ◽  
Shear Stresses ◽  
Fe Model ◽  
Cerebral Vasculature ◽  
Blast Exposure ◽  
Indirect Mechanism ◽  
Wall Shear ◽  
The Brain

The interaction of explosion-induced blast waves with the torso is suspected to contribute to brain injury. In this indirect mechanism, the wave-torso interaction is assumed to generate a blood surge, which ultimately reaches and damages the brain. However, this hypothesis has not been comprehensively and systematically investigated, and the potential role, if any, of the indirect mechanism in causing brain injury remains unclear. In this interdisciplinary study, we performed experiments and developed mathematical models to address this knowledge gap. First, we conducted blast-wave exposures of Sprague-Dawley rats in a shock tube at incident overpressures of 70 and 130 kPa, where we measured carotid-artery and brain pressures while limiting exposure to the torso. Then, we developed three-dimensional (3-D) fluid-structure interaction (FSI) models of the neck and cerebral vasculature and, using the measured carotid-artery pressures, performed simulations to predict mass flow rates and wall shear stresses in the cerebral vasculature. Finally, we developed a 3-D finite element (FE) model of the brain and used the FSI-computed vasculature pressures to drive the FE model to quantify the blast-exposure effects in the brain tissue. The measurements from the torso-only exposure experiments revealed marginal increases in the peak carotid-artery overpressures (from 13.1 to 28.9 kPa). Yet, relative to the blast-free, normotensive condition, the FSI simulations for the blast exposures predicted increases in the peak mass flow rate of up to 255% at the base of the brain and increases in the wall shear stress of up to 289% on the cerebral vasculature. In contrast, our simulations suggest that the effect of the indirect mechanism on the brain-tissue-strain response is negligible (&lt;1%). In summary, our analyses show that the indirect mechanism causes a sudden and abundant stream of blood to rapidly propagate from the torso through the neck to the cerebral vasculature. This blood surge causes a considerable increase in the wall shear stresses in the brain vasculature network, which may lead to functional and structural effects on the cerebral veins and arteries, ultimately leading to vascular pathology. In contrast, our findings do not support the notion of strain-induced brain-tissue damage due to the indirect mechanism.

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