Brain Tissue Damage Research Articles

Migratory Response of Cells in Neurogenic Niches to Neuronal Death: The Onset of Harmonic Repair?

Harmonic mechanisms orchestrate neurogenesis in the healthy brain within specific neurogenic niches, which generate neurons from neural stem cells as a homeostatic mechanism. These newly generated neurons integrate into existing neuronal circuits to participate in different brain tasks. Despite the mechanisms that protect the mammalian brain, this organ is susceptible to many different types of damage that result in the loss of neuronal tissue and therefore in alterations in the functionality of the affected regions. Nevertheless, the mammalian brain has developed mechanisms to respond to these injuries, potentiating its capacity to generate new neurons from neural stem cells and altering the homeostatic processes that occur in neurogenic niches. These alterations may lead to the generation of new neurons within the damaged brain regions. Notwithstanding, the activation of these repair mechanisms, regeneration of neuronal tissue within brain injuries does not naturally occur. In this review, we discuss how the different neurogenic niches respond to different types of brain injuries, focusing on the capacity of the progenitors generated in these niches to migrate to the injured regions and activate repair mechanisms. We conclude that the search for pharmacological drugs that stimulate the migration of newly generated neurons to brain injuries may result in the development of therapies to repair the damaged brain tissue.

Dietary vitamin B12 deficiency impairs motor function and changes neuronal survival and choline metabolism after ischemic stroke in middle-aged male and female mice

ABSTRACT Nutrition is a modifiable risk factor for ischemic stroke. As people age their ability to absorb some nutrients decreases, a primary example is vitamin B12. Older individuals with a vitamin B12 deficiency are at a higher risk for ischemic stroke and have worse stroke outcome. However, the mechanisms through which these occur remain unknown. The aim of the study was to investigate the role of vitamin B12 deficiency in ischemic stroke outcome and mechanistic changes in a mouse model. Ten-month-old male and female mice were put on control or vitamin B12 deficient diets for 4 weeks prior to and after ischemic stroke to the sensorimotor cortex. Motor function was measured, and tissues were collected to assess potential mechanisms. All deficient mice had increased levels of total homocysteine in plasma and liver tissues. After ischemic stroke, deficient mice had impaired motor function compared to control mice. There was no difference between groups in ischemic damage volume. However, within the ischemic damage region, there was an increase in total apoptosis of male deficient mice compared to controls. Furthermore, there was an increase in neuronal survival in ischemic brain tissue of the vitamin B12 deficient mice compared to controls. Additionally, there were changes in choline metabolites in ischemic brain tissue because of a vitamin B12 deficiency. The data presented in this study confirms that a vitamin B12 deficiency worsens stroke outcome in male and female mice. The mechanisms driving this change may be a result of neuronal survival and compensation in choline metabolism within the damaged brain tissue.

Blood redistribution preferentially protects vital organs under hypoxic stress in Pelteobagrus vachelli

Blood redistribution occurs in mammals under hypoxia but has not been reported in fish. This study investigated the tissue damage, hypoxia-inducible factor (HIF) activation level, and blood flow changes in the brain, liver, and muscle of Pelteobagrus vachelli during the hypoxia process for normoxia-hypoxia-asphyxia. The results showed that P. vachelli has tissue specificity in response to hypoxic stress. Cerebral blood flow increased with less damage than in the liver and muscle, suggesting that P. vachelli may also have a blood redistribution mechanism in response to hypoxia. It is worth noting that severe hypoxia can lead to a sudden increase in the degree of brain tissue damage. In addition, higher dissolved oxygen levels activate HIF and may have contributed to the reduced damage observed in the brain. This study provides basic data for investigating hypoxic stress in fish.

Real-Time PCR Quantification of 87 miRNAs from Cerebrospinal Fluid: miRNA Dynamics and Association with Extracellular Vesicles after Severe Traumatic Brain Injury

Severe traumatic brain injury (sTBI) is an intracranial damage triggered by external force, most commonly due to falls and traffic accidents. The initial brain injury can progress into a secondary injury involving numerous pathophysiological processes. The resulting sTBI dynamics makes the treatment challenging and prompts the improved understanding of underlying intracranial processes. Here, we analysed how extracellular microRNAs (miRNAs) are affected by sTBI. We collected thirty-five cerebrospinal fluids (CSF) from five sTBI patients during twelve days (d) after the injury and combined them into d1-2, d3-4, d5-6 and d7-12 CSF pools. After miRNA isolation and cDNA synthesis with added quantification spike-ins, we applied a real-time PCR-array targeting 87 miRNAs. We detected all of the targeted miRNAs, with totals ranging from several nanograms to less than a femtogram, with the highest levels found at d1-2 followed by decreasing levels in later CSF pools. The most abundant miRNAs were miR-451a, miR-16-5p, miR-144-3p, miR-20a-5p, let-7b-5p, miR-15a-5p, and miR-21-5p. After separating CSF by size-exclusion chromatography, most miRNAs were associated with free proteins, while miR-142-3p, miR-204-5p, and miR-223-3p were identified as the cargo of CD81-enriched extracellular vesicles, as characterised by immunodetection and tunable resistive pulse sensing. Our results indicate that miRNAs might be informative about both brain tissue damage and recovery after sTBI.

Ballistic study on the penetration potential and injury potential of different bullet types in the use of a newly developed bullet shooting stunner for adequate stunning of heavy cattle.

Recently, a special bullet shooting stunner for heavy cattle has been developed that fires a bullet instead of a bolt. In the search for a suitable ammunition, the following criteria must be met: First, the energy of the bullet must be sufficient to penetrate the thick frontal bones of heavy cattle. Second, the injury potential at the corresponding penetration depth should preferably be large in order to damage brain tissue relevant to stunning. Third, the bullet must not perforate the occipital bone (over-penetration). Four different bullet types [Hornady FTX, Hydra-Shok, Black Mamba, and a common full metal jacket (FMJ) bullet] were evaluated in a series of experiments on soap blocks and removed bone plates followed by computed tomography examinations. Penetration potential was evaluated in terms of kinetic energy relative to the caliber of the bullet, i.e., mean energy density (ED). Injury potential was evaluated by the mean extent of the cavity volume (e CV ) at the relevant penetration depth of 5.5 to 7.5 cm in the soap block. All four bullet types passed through the frontal bone plate. The ED was 17.50 J/mm2 (Hornady FTX), 17.46 J/mm2 (Hydra-Shok), 13.47 J/mm2 (Black Mamba), and 13.47 J/mm2 (FMJ). The Hornady FTX and the Hydra-Shok each fragmented heavily. The FMJ was excluded after three experiments due to over-penetrations. The e CV was e CV = 3.77 cm2 (Hornady FTX), 2.71 cm2 (Hydra-Shok), and 1.31 cm2 (Black Mamba), with a significant difference (p = 0.006) between the Hornady FTX and the Black Mamba. For use in heavy cattle, the Hornady FTX and the Hydra-Shok are recommended due to the larger e CV than the Black Mamba.

The neurotoxicity and mechanism of TBBPA-DHEE exposure in mature zebrafish (Danio rerio)

Tetrabromobisphenol A-bis (2-hydroxyethyl) ether (TBBPA-DHEE) has been detected in various environmental media and organisms, and its ecological risks and health hazards have attracted great attention, but sufficient toxicological data have not proved the toxic effects of TBBPA-DHEE exposure on aquatic organism. In this study, the neurotoxicity and mechanism of zebrafish (3-month-old) exposed to TBBPA-DHEE (0.86 μg/L, 12.9 μg/L, 193.5 μg/L) were studied. Furthermore, the neurotoxicity susceptibility of different sexes of zebrafish was revealed. Behavioral studies revealed that TBBPA-DHEE exposure has significant differences in average speed, duration of mania, the distance between objects, and ATP content between male and female zebrafish. Slight damage in brain tissue of male zebrafish was found. The transcriptome analysis revealed that the molecular mechanism of neurotoxicity in mature female and male zebrafish is different. For mature female zebrafish, TBBPA-DHEE significantly affected the expression of genes related to behavior and development, and its mechanism may be that it can produce neurotoxicity by affecting related genes in the hormone, synapse, and Ca2+ signaling pathway. For mature male zebrafish, TBBPA-DHEE can significantly affect their behavior and expression of nerve-related genes. Results from the transcriptomic analysis suggests that the possible molecular mechanism may be through the inhibition of Ca2+ signal transmission and produce neurotoxicity by affecting the expression of related genes in neural synapses, Ca2+ signal, and MAPK signal in brain tissue of zebrafish. The results suggested that exposure to low-dose TBBPA-DHEE could induce neurotoxicity in zebrafish, and female and male zebrafish showed different toxic effects and molecular mechanisms.

PI3K-Akt signaling pathway based on network pharmacology for the anti-Alzheimer's disease effect of licorice stem flavonoids.

Active ingredients were screened by TCMSP and swissADME, meanwhile, PharmMapper combined with UniProt database was used to predict the active ingredient target information, GeneCard database was employed to obtain Alzheimer's disease (AD)-related genes, Cytoscapes 3.7.2 software was utilized to map the active ingredient-target effect. Besides, Cytoscapes 3.7.2 software Bisogenet and Cyto NCA plug-in combined with STRING platform were utilized to map the protein-protein interaction (PPI) network, DAVID was employed for GO annotation, while KEGG plug-in was used for KEGG pathway enrichment. Mice were tested for inflammatory damage induced by intracerebral injection of lipopolysaccharide (LPS), as well as learning memory and anxiety by water maze and open field tests. In addition, the expression of Caspase-3 and Caspase-9, together with inflammatory factors TNF-α, IL-6, and IL-1β was analyzed in serum. The expression levels of proteins related to PI3K-Akt signaling pathway in the brain were detected by Western blot (WB) assay. According to the results of network pharmacology, there were 35 active ingredients of licorice stem and leaf flavonoids screened, which exerted the anti-Alzheimer's disease (AD) effects via 67 targets and activated 41 signaling pathways including the PI3K-Akt pathway. Furthermore, Behavioural results revealed that Licorice stem and leaf flavonoids improved the learning and memory abilities of model mice and significantly improved the anxiety caused by inflammatory brain damage. Moreover, as suggested by HE staining and TUNEL staining of brain sections, Glycyrrhiza glabra stem and leaf flavonoids alleviated morphological lesions and cell nuclear damage in brain tissue. Results: of brain homogenate supernatant assay demonstrated that Glycyrrhiza glabra stem and leaf flavonoids had a significant effect on the levels of oxidative indicators superoxide dismutase (SOD), catalase (CAT), malonaldehyde (MDA), acetylcholine (Ach), acetylcholinesterase (AchE), Caspase-3, Caspase-9 and serum inflammatory factors TNF-α, IL-6 and IL-1β. Additionally, WB assay results indicated that the PI3K-Akt signaling pathway was activated.

Evaluating the effect of ginsenoside Rg1 on CPF-induced brain injury in mice via PI3k/AKT pathway.

Organophosphorus pesticides (OPs) have long been used extensively on agricultural land and can lead to significant improvements in crop yields. Due to occupational exposure, humans are exposed to pesticides through dermal contact, inhalation, and ingestion. The effects of OPs on the organism are currently studied for their effects on livers, kidneys, hearts, blood indicators, neurotoxicity,and teratogenic, carcinogenic, and mutagenic effects, while studies in the direction of brain tissue damage have not been reported in detail. Previous reports have confirmed that ginsenoside Rg1 is a prominent and representative tetracyclic triterpenoid derivative rich in ginseng and has good neuroprotective activity. Considering that, the aim of this study was to establish a mouse model of brain tissue injury by using the OP-type pesticide chlorpyrifos (CPF) and to explore the therapeutic effects and possible molecular mechanisms of Rg1. Mice in the experimental group were pre-protected with Rg1 by gavage for 1 week, and brain tissue damage was induced using CPF (5 mg/kg for 1 week) to assess the effect of Rg1 (80 and160 mg/kg for 3 weeks) in alleviating brain damage. Morris water maze and histopathological analysis were performed to assess cognitive function and pathological changes in the mouse brain, respectively. Protein expression levels of Bax, Bcl-2, Caspase-3, Cl-Cas-3, Caspase-9, Cl-Cas-9, phosphoinositide 3-kinase (PI3K), phosphorylated-PI3K, protein kinase B (AKT), and phosphorylated-AKT were quantified by protein blotting analysis. Rg1 obviously restored CPF-induced oxidative stress damage in mouse brain tissue, increased the levels of antioxidant parameters (total superoxide dismutase, total antioxidative capacity, and glutathione) in the brain, and significantly reduced the overexpression of apoptosis-related proteins induced by CPF. At the same time, Rg1 also markedly attenuated the histopathological changes in the brain induced by CPF exposure. Mechanistically, Rg1 could effectively activate the phosphorylation of PI3K/AKT. Furthermore, molecular docking studies revealed a stronger binding capacity between Rg1 and PI3K. Rg1 attenuated neurobehavioural alterations and reduced lipid peroxidation in the mouse brain to a great extent. Apart from that, Rg1 administration improved brain histopathology in CPF-induced rats. All results suggest that ginsenoside Rg1 has potential antioxidant effects on CPF-induced oxidative brain injury, and it is evident that Rg1 could be used as a promising therapeutic strategy for the study of brain injury from OPpoisoning.

Insights into the pharmacodynamics and pharmacokinetics of meldonium after exposure to acute high altitude.

Objective: Meldonium, a well-known cardioprotective drug, has been reported to be protective against pulmonary injury at high altitudes; however, the pharmacodynamics of meldonium in other vital organs under acute high-altitude injury are less investigated and the related pharmacokinetics have not been fully elucidated. Methods and Results: The present study examined the basic pharmacodynamics and pharmacokinetics (PK) in rat exposure to acute high-altitude hypoxia after intragastrical and intravenous pre-administration of meldonium. The results indicate that meldonium can improve acute hypoxia-induced pathological damage in brain and lung tissues, and restore blood biochemistry and routine blood index of heart, liver and kidney tissues under a simulated acute high-altitude environment. Furthermore, compared to the normoxia group, rats exposed to simulated high-altitude hypoxia and premedicated with intragastrical meldonium showed linear kinetics in the dose range of 25-100mg/kg, with a significantly increase in the area under curve (AUC) and reduced clearance rate. No significant differences in these meldonium of PK parameters were observed with intravenous administration. Additionally, meldonium was involved in the regulation of succinic acid and 3-hydroxypropionic acid. Conclusion: These results will contribute to our understanding of the preclinical PK properties of meldonium and its acute high-altitude protective effects.

Elabela-APJ axis mediates angiogenesis via YAP/TAZ pathway in cerebral ischemia/reperfusion injury

Angiogenesis helps to improve neurological recovery by repairing damaged brain tissue and restoring cerebral blood flow (CBF). The role of the Elabela (ELA)-Apelin receptor (APJ) system in angiogenesis has gained much attention. We aimed to investigate the function of endothelial ELA on post-ischemic cerebral angiogenesis. Here, we demonstrated that the endothelial ELA expression was upregulated in the ischemic brain and treatment with ELA-32 mitigated brain injury and enhanced the restoration of CBF and newly formed functional vessels following cerebral ischemia/reperfusion (I/R) injury. Furthermore, ELA-32 incubation potentiated proliferation, migration, and tube formation abilities of the mouse brain endothelial cells (bEnd.3 cells) under oxygen-glucose deprivation/reoxygenation (OGD/R) condition. RNA sequencing analysis indicated that ELA-32 incubation had a role in the Hippo signaling pathway, and improved angiogenesis-related gene expression in OGD/R-exposed bEnd.3 cells. Mechanistically, we depicted that ELA could bind to APJ and subsequently activate YAP/TAZ signaling pathway. Silence of APJ or pharmacological blockade of YAP abolished the pro-angiogenesis effects of ELA-32. Together, these findings highlight the ELA-APJ axis as a potential therapeutic strategy for ischemic stroke by showing how activation of this pathway promotes post-stroke angiogenesis.

In vivo characterization of cerebrovascular impairment induced by amyloid β peptide overload in glymphatic clearance system using swept-source optical coherence tomography.

Antiamyloid ( ) immunotherapy is a promising therapeutic strategy for Alzheimer's disease (AD) but generates large amounts of soluble peptides that could overwhelm the clearance pathway, leading to serious side effects. Direct implications of in glymphatic drainage transport for cerebral vasculature and tissue are not well known. Studies are needed to resolve this issue and pave the way to better monitoring abnormal vascular events that may occur in -modifying therapies for AD. The objective is to characterize the modification of cerebral vasculature and tissue induced by soluble abundantly present in the glymphatic clearance system. peptide was injected intracerebroventricularly and swept-source optical coherence tomography (SS-OCT) was used to monitor the progression of changes in the brain microvascular network and tissue in vivo over 14 days. Parameters reflecting vascular morphology and structure as well as tissue status were quantified and compared before treatment. Vascular perfusion density, vessel length, and branch density decreased sharply and persistently following peptide administration. In comparison, vascular average diameter and vascular tortuosity were moderately increased at the late stage of monitoring. Endpoint density gradually increased, and the global optical attenuation coefficient value decreased significantly over time. burden in the glymphatic system directly contributes to cerebrovascular structural and morphological abnormalities and global brain tissue damage, suggesting severe deleterious properties of soluble cerebrospinal fluid- . We also show that OCT can be used as an effective tool to monitor cerebrovascular dynamics and tissue property changes in response to therapeutic treatments in drug discovery research.

Phospholipase B Is Critical for Cryptococcus neoformans Survival in the Central Nervous System.

Cryptococcus neoformans (Cn) is an opportunistic, encapsulated, yeast-like fungus that causes severe meningoencephalitis, especially in countries with high HIV prevalence. In addition to its well-known polysaccharide capsule, Cn has other virulence factors such as phospholipases, a heterogeneous group of enzymes that hydrolyze ester linkages in glycerophospholipids. Phospholipase B (PLB1) has been demonstrated to play a key role in Cn pathogenicity. In this study, we used a PLB1 mutant (plb1) and its reconstituted strain (Rec1) to assess the importance of this enzyme on Cn brain infection in vivo and in vitro. Mice infected with the plb1 strain survive significantly longer, have lower peripheral and central nervous system (CNS) fungal loads, and have fewer and smaller cryptococcomas or biofilm-like brain lesions compared to H99- and Rec1-infected animals. PLB1 causes extensive brain tissue damage and changes microglia morphology during cryptococcal disease, observations which can have important implications in patients with altered mental status or dementia as these manifestations are related to poorer survival outcomes. plb1 cryptococci are significantly more phagocytosed and killed by NR-9460 microglia-like cells. plb1 cells have altered capsular polysaccharide biophysical properties which impair their ability to stimulate glial cell responses or morphological changes. Here, we provide significant evidence demonstrating that Cn PLB1 is an important virulence factor for fungal colonization of and survival in the CNS as well as in the progression of cryptococcal meningoencephalitis. These findings may potentially help fill in a gap of knowledge in our understanding of cerebral cryptococcosis and provide novel research avenues in Cn pathogenesis. IMPORTANCE Cryptococcal meningoencephalitis (CME) is a serious disease caused by infection by the neurotropic fungal pathogen Cryptococcus neoformans. Due to the increasing number of cases in HIV-infected individuals, as well as the limited therapies available, investigation into potential targets for new therapeutics has become critical. Phospholipase B is an enzyme synthesized by Cn that confers virulence to the fungus through capsular enlargement, immunomodulation, and intracellular replication. In this study, we examined the properties of PLB1 by comparing infection of a Cn PLB1 mutant strain with both the wild-type and a PLB1-reconstituted strain. We show that PLB1 augments the survival and proliferation of the fungus in the CNS and strengthens virulence by modulating the immune response and enhancing specific biophysical properties of the fungus. PLB1 expression causes brain tissue damage and impacts glial cell functions, which may be responsible for the dementia observed in patients which may persist even after resolving from CME. The implications of PLB1 inhibition reveal its involvement in Cn infection and suggest that it may be a possible molecular target in the development of antifungal therapies. The results of this study support additional investigation into the mechanism of PLB1 to further understand the intricacies of cerebral Cn infection.

Acute Microbleeds and Microinfarcts Within the Perihematomal Area After Intracerebral Hemorrhage.

To further our understanding of the pathophysiology of spontaneous intracerebral hemorrhage (ICH) and related injury, we provided a postmortem neuropathological examination of acute microvascular lesions (microbleeds and microinfarcts) within the perihematomal area. We included all consecutive cases (2005-2019) from the Lille University Hospital brain bank of ICH patients who died within the first month. Paraffin-embedded tissue sections from the perihematomal area were processed for several stainings and immunolabelings to investigate the presence of acute microbleeds and microinfarcts in the perihematomal area and to characterize surrounding neuronal and systemic inflammatory reaction (macrophages and neutrophils). We included 14 ICH cases (median age, 78 years; 10 females). Acute microbleeds were observed in the perihematomal area in 12/14 patients (86%, ranging from 1 through >10) and microinfarcts in 5/14 (36%, ranging from 1 through 4). Microbleeds were observed whatever the delay from ICH onset to death was, while most cases with acute microinfarcts were observed between day 3 and day 7 (n=3/5). Both lesions were characterized by an abundant accumulation of systemic inflammatory cells and necrotic areas. Acute microbleeds and microinfarcts might contribute to the propagation of secondary brain tissue damages after ICH. Our examinations also question the potential role of massive systemic inflammatory cells recruitment in the genesis of these microvascular injuries.

Royal jelly protects brain tissue against fluoride-induced damage by activating Bcl-2/NF-κB/caspase-3/caspase-6/Bax and Erk signaling pathways in rats.

This study is aimed at determining whether royal jelly (RJ) which has a powerful antioxidant property prevents fluoride-induced brain tissue damage and exploring whether Bcl-2/NF-κB/ and caspase-3/caspase-6/Bax/Erk pathways play a critical role in the neuroprotective effect of RJ. Wistar albino rats were chosen for the study, and they were randomly distributed into six groups: (i) control; (ii) royal jelly; (iii) fluoride-50; (iv) fluoride-100; (v) fluoride-50 + royal jelly; (vi) fluoride-100 + royal jelly. We established fluoride-induced brain tissue damage with 8-week-old male Wistar albino rats by administration of fluoride exposure (either 50mg/kg or 100mg/kg bw) through drinking water for 8weeks. Then, the study duration is for 56days where the rats were treated with or without RJ (100mg/kg bw) through oral gavage. The effects of RJ on glutathione (GSH), catalaseactivity (CAT), and malondialdehyde (MDA) levels were determined via spectrophotometer. Western blot analysis was performed to investigate the effectsof royal jelly on the protein expression levels of Bax, caspase-3, caspase-6, Bcl-2, NF-κB, COX-2, and Erk. It was also studied the effects of RJ on histopathological alterations in fluoride-induced damage to the rat brain. As a result,the Bcl-2, NF-κB, and COX-2 protein expression levels were increased in the fluoride-treated (50 and 100mg/kg) groups but theywere decreased significantly by RJ treatment in the brain tissue. Additionally, the protein expression of caspase-3, caspase-6, Bax, and Erk were decreased in fluoride-treated groups and theywere significantly increased by RJ treatment compared to theun-treated rats. Our results suggested that RJ prevented fluoride-induced brain tissue damage through anti-antioxidant activities.

Changes in brain gray matter volume in nasopharyngeal carcinoma patients after radiotherapy in long-term follow-up

ObjectivesThe aim of this study was to examine the changes in gray matter in nasopharyngeal carcinoma patients with normal hearing (Group 1) and nasopharyngeal carcinoma patients with hearing loss (Group 2) after radiotherapy using voxel-based morphological analysis and to analyze the relationship with the radiation doses of the temporal lobe. Methods21 patients in Group 1, 14 patients in Group 2, and 21 healthy volunteers were selected. All participants underwent an otologic examination and three-dimensional magnetization preparatory rapid acquisition gradient echo sequence scan. The correlation between the variation of whole brain gray matter volume and the doses of the temporal lobe was analyzed by Data Processing & Analysis for Brain Imaging software. ResultsCompared with the normal control group, the brain areas with reduced gray matter volume in nasopharyngeal carcinoma patients after radiotherapy were mainly in the left posterior cerebellar lobe (T = −8.797), left insular lobe (T = −7.96), and the right insular lobe (T = −6.632). Compared to Group 1, the brain areas of Group 2 patients with reduced gray matter volume were mainly in the left superior temporal gyrus (T = −2.366), left olfactory bulb (T = −2.52), left Rolandic operculum (T = −2.431), and right olfactory bulb (T = −3.100). Compared with Group 1, the brain areas of Group 2 patients with increased gray matter volume were mainly in the left calcarine sulcus (T=3.425) and right calcarine sulcus (T=3.169). There were no correlations between the changes of brain gray matter volume and the radiation doses of the temporal lobe in both Group 1 and Group 2. ConclusionsThe radiotherapy may cause the changes of brain areas associated with cognitive function in nasopharyngeal carcinoma in a long-term follow-up. At the same time, nasopharyngeal carcinoma patients with the radiation-induced hearing loss had abnormal gray matter volumes in the auditory center and other sensory centers. Our findings might provide new understanding into the pathogenesis of radiation-induced brain damage in normal-appearing brain tissue. Yet this exploratory study should be taken with caution.

Extracellular Vesicles Derived from Bone Mesenchymal Stem Cells Carrying circ_0000075 Relieves Cerebral Ischemic Injury by Competitively Inhibiting miR-218-5p and Up-regulating E3 Ubiquitin Ligase SMURF2.

Extracellular vesicle (EV)-encapsulated circRNAs have the potential role in affecting brain disorders. However, the role of circ_0000075 in cerebral ischemic injury remains unclear. Here, we tried to investigate the mechanism of bone marrow mesenchymal stem cell (BMSC)-derived EVs carrying circ_0000075 in the control of cerebral ischemic injury. Initially, a mouse model with cerebral ischemic injury was induced by middle cerebral artery occlusion (MCAO), followed by the determination of circ_0000075 expression. Then, neurons were isolated and subjected to oxygen-glucose deprivation/reperfusion. BMSCs were isolated for extraction of EVs. The correlation among circ_0000075, microRNA (miR)-218-5p, and Smad ubiquitination regulatory factor 2 (SMURF2) was detected with their roles in cerebral ischemic injury analyzed in vivo and in vitro. circ_0000075 was down-regulated in MCAO mice and engineered RVG-EVs were internalized by neurons to up-regulate circ_0000075 expression. Treatment of RVG-circ_0000075-EVs reduced brain tissue damage, increased neuronal count, and significantly curtailed apoptosis rate, suppressing cerebral ischemic injury in vitro and in vivo. miR-218-5p was targeted by circ_0000075 in neurons, which promoted SMURF2 expression. A negative correlation between SMURF2 and transcriptional regulator Yin Yang 1 (YY1) was identified. In vitro experiments further proved that circ_ 00,000 75 could down-regulate the expression of YY1 through SMURF2, and finally relieving cerebral ischemic injury. Collectively, engineered EVs delivered circ_0000075 into brain tissues and increased circ_0000075 expression, which down-regulated miR-218-5p and up-regulated SMURF2, thus alleviating cerebral ischemic injury.

Acceptability of neural stem cell therapy for cerebral palsy: survey of the Australian cerebral palsy community

BackgroundNeural stem cells (NSCs) have the potential to engraft and replace damaged brain tissue, repairing the damaged neonatal brain that causes cerebral palsy (CP). There are procedures that could increase engraftment of NSCs and may be critical for efficacy, but hold notable risks. Before clinical trials progress, it is important to engage with the CP community to understand their opinions. The aim of this study was to determine the acceptability of NSC therapy for CP in the CP community.MethodsAustralian residents with CP and parents/carers of those with CP completed a questionnaire to determine their willingness to use NSCs from three sources (fetal, embryonic and induced pluripotent stem cells) and their willingness to undergo accompanying procedures (neurosurgery, immunosuppression) that carry potential risks. To further explore their views, participants also answered free text questions about their ethical concerns regarding the source of NSCs and their perceptions of meaningful outcomes following NSC treatment.ResultsIn total, 232 responses were analyzed. Participants were willing to use NSCs from all three cell sources and were willing to undergo NSC therapy despite the need for neurosurgery and immunosuppression. Participants identified a range of outcome domains considered important following NSC treatment including gross motor function, quality of life, independence and cognitive function.ConclusionsHypothetical NSC therapy was acceptable to the Australian CP community. This study has identified important findings from the CP community which can be used to inform future NSC research, including the design of clinical trials which may help to increase recruitment, compliance and participant satisfaction.

The Effect and Mechanism of Syringa pinnatifolia Hemsl. Ligans on Cerebral Ischemia-Reperfusion Injury and Oxidative Stress in Mice.

Lignans are the main components of Syringa pinnatifolia Hemsl. (SP). Previous studies have shown that SP lignans (SPL) can considerably improve CCl4-induced acute liver injury in mice by the anti-oxidative stress (OS) mechanism. In this study, we investigated the antioxidant effects of SPL on cerebral ischemia/reperfusion injury (CIRI) and its underlying molecular mechanism. We developed a middle cerebral artery occlusion/reperfusion (MCAO/R) model in mice to achieve CIRI and orally administered SPL daily for 1-3 days. We evaluated neurological function deficits and performed hematoxylin and eosin staining. We further calculated the infarct volume. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the brain were detected using corresponding kits. The transcription and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and NAD(P)H quinone dehydrogenase 1 (NQO1) in brain tissues were analyzed by real-time reverse transcription polymerase chain reaction and western blotting, respectively. The results showed that SPL could remarkably ameliorate neurological functions and pathological damage in brain tissues, reducing the cerebral infarct volume. It also increased the SOD and GPx activities decreased the MDA levels as well as inhibited the expression of (NOX)2 and NOX4. We also found that the mRNA and protein levels of Nrf2, HO-1, and NQO1 in the CIRI mice increased transiently and peaked at 24h of reperfusion, and then began to decline. SPL could reverse decreasing Nrf2 and HO-1 levels after 24h. In conclusion, SPL can alleviate CIRI and OS by activating the Nrf2/HO-1 pathway.

Protective effect of lactoferrin administration against brain tissue damage in diabetic rats

Bovine lactoferrin (bLf), a glycoprotein with iron, Several of Lf's functions intervene through various cell receptors. Its antibacterial, antiparasitic, anti-inflammatory, and antioxidant effects Additionally, it has been found that Lf has immunomodulating. We looked into the protective effects of Lf on various brain tissue indicators and histopathological examination of streptozotocin (STZ) induced diabetic rats. This research aimed to check the potential protective effect of lactoferrin verses brain lesion in STZ induced diabetic rat. The rats were split into five groups: Control (C), Diabetic rat (T2D), T2D + Insulin, T2D + Lactoferrin, and T2D + Insulin + Lactoferrin. Diabetes was created in rat groups by administration STZ (60 mg/kg body weight), then rat was sacrificed. The tissues of the Brain and serum had been chosen to analyze biochemical brain tissue indicators, Serum Neuron-Specific Enolase (SNE), Serum Brain-Derived Neurotrophic Factor (BDNF), and Tissue Necrosis Factor-Alpha (TNF-Alpha). Also, H&E staining was utilized to measure the histological changes of the brain and Comet assay of brain tissue samples for detection of DNA damage. In T2D rat, Lactoferrin corrected aberrant serum levels of SNE, BDNF and TNF-Alpha, in addition, Lactoferrin improves brain pathological changes might be through hypoglycemic, and/or anti-inflammatory actions and reduced DNA damage as compared to diabetic untreated rats. It could be concluded that oral administration of lactoferrin to diabetic rats alone or in combination with insulin treatment for six weeks was found to attenuate the harmful effects of diabetes on brain biomarkers as well as the pathological lesions that occur in the brain tissues of diabetic rats.

Methylmalonic acidemia: Neurodevelopment and neuroimaging.

Methylmalonic acidemia (MMA) is a genetic disease of abnormal organic acid metabolism, which is one of the important factors affecting the survival rate and quality of life of newborns or infants. Early detection and diagnosis are particularly important. The diagnosis of MMA mainly depends on clinical symptoms, newborn screening, biochemical detection, gene sequencing and neuroimaging diagnosis. The accumulation of methylmalonic acid and other metabolites in the body of patients causes brain tissue damage, which can manifest as various degrees of intellectual disability and severe neurological dysfunction. Neuroimaging examination has important clinical significance in the diagnosis and prognosis of MMA. This review mainly reviews the etiology, pathogenesis, and nervous system development, especially the neuroimaging features of MMA.