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Obstetrics and Gynecology Research 2023Cerebral Palsy (CP), the most common cause of disability in children, is phenotypically heterogeneous. Approximately 20% of cases develop severe scoliosis. A...
INTRODUCTION
Cerebral Palsy (CP), the most common cause of disability in children, is phenotypically heterogeneous. Approximately 20% of cases develop severe scoliosis. A pathological hallmark of CP is periventricular leukomalacia (PVL), which is due to dysmyelination, suggesting the possibility of a lipidomic abnormality. Risk factors for CP include perinatal hypoxia, prematurity, multiple gestation, ischemia, infection, and maternal alcohol consumption. There is evidence for low serum levels of omega-3 (ω-3) fatty acids in CP patients, and separately in idiopathic scoliosis. Many effects of free fatty acids (FFAs) are mediated via specific G protein-coupled free fatty acid receptors (FFARs), which play essential roles as nutritional and signaling molecules. FFAs, including ω-3, and their receptors are involved in the development and metabolism of oligodendrocytes (OLs), and are critical to myelination. Thus, the cases of CP that will develop severe scoliosis might be those in which there is a deficiency of ω-3, FFARs, or other lipidomic abnormality that is detectable early in the plasma. If so, we might be able to predict scoliosis and prevent it with dietary supplementation.
METHODS
Blood samples were collected from four groups of patients at the Philadelphia Shriners Children's Hospital (SCH-P): 1) patients with CP; 2) severe scoliosis (>40o); 3) CP plus scoliosis; and 4) non-impaired controls stratified by age (2-18 yrs), gender, and race/ethnicity, under an IRB-approved protocol. Serum proteins and RNA were purified, and OL-derived exosomes (OL-Es) isolated, using myelin basic protein (MBP) as a late OL marker. Protein was used for the detection of MBP and FFAR by enzyme-linked immunosorbent assays (ELISAs), and by flow cytometry. RNA was assayed by digital droplet polymerase chain reaction (ddPCR) for OL markers and FFAR expression.
RESULTS
FFAR and MBP proteins were downregulated in each of the three patient groups compared to controls, and this difference was greatest in both patients with CP plus scoliosis.
CONCLUSION
Altogether, MBP and FFAR levels were reduced in OL-Es from both children with CP plus scoliosis. The lipid abnormalities specific to CP with scoliosis were concentrated in OLs. Our data might i) suggest therapeutic targets to reduce dysmyelination and scoliosis in CP, ii) predict which children are at risk for developing scoliosis, iii) lead to therapeutic trials of fatty acids for CP and other dysmyelinating neurological disorders.
PubMed: 37538811
DOI: 10.26502/ogr0127 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Aug 2023Globular placenta is a rare type of abnormal placental morphology. It shows small placental volume and placental thickening on imaging, and the placental edge is round...
Globular placenta is a rare type of abnormal placental morphology. It shows small placental volume and placental thickening on imaging, and the placental edge is round and blunt. Some studies have pointed out that it may be due to the invasion of superficial villi into maternal tissue and insufficient transformation of spiral arterioles. It leads to placental ischemia, and early poor perfusion causes abnormal placenta morphology, which is manifested as fibrin deposition around the villi under the microscope. Because the effective exchange area of the globular placenta is smaller than that of the normal placenta, its influence on the fetus gradually appears with the increase of gestational age. Studies have observed that placental volume and placental thickness are associated with fetal growth restriction during pregnancy. Growth-restricted fetuses are at increased risk for perinatal diseases such as intraventricular hemorrhage, periventricular leukomalacia, respiratory distress syndrome, necrotizing enterocolitis, etc. Hemodynamic parameters will reflect the problem of placental perfusion, such as the peak systolic/diastolic blood flow of the uterine artery and umbilical artery, etc. During pregnancy, these two ultrasound indicators and placental morphology should be monitored to detect the disease at an early stage and in the early stage of disease progression. The use of drug intervention may improve perinatal outcomes, but the current clinical evidence is insufficient. Most physicians use empirical treatment, that is, to improve placental circulation and increase perfusion, but there is currently no obvious effective drug. There is no consensus on the doses of drugs such as aspirin and heparin, and the reported obstetric outcomes vary from study to study. In order to better treat these diseases, provide more adequate clinical data, and lay the foundation for further research in the later period, this report describes a young woman who was treated in our hospital. This report describes a young woman who presented to our hospital with a thickening of the placenta on mid-trimester ultrasonography, aggressive use of drug therapy and close follow-up when the fetus did not lag behind, and who developed fetal lag in the third trimester and was accompanied by The fetus was hemodynamically abnormal, and a live birth was obtained after timely termination of the pregnancy, but early necrotizing enteritis developed. Finally, we combined the literature review to understand the pathological mechanism, clinical characteristics, disease prognosis and corresponding treatment methods of the disease.
Topics: Pregnancy; Female; Humans; Infant, Newborn; Placenta; Fetal Growth Retardation; Ultrasonography; Prognosis; Infarction; Ultrasonography, Prenatal
PubMed: 37534664
DOI: 10.19723/j.issn.1671-167X.2023.04.031 -
European Journal of Pediatrics Oct 2023This study aims to assess the impact of time of onset and features of early foetal growth restriction (FGR) with absent end-diastolic flow (AEDF) on pregnancy outcomes...
This study aims to assess the impact of time of onset and features of early foetal growth restriction (FGR) with absent end-diastolic flow (AEDF) on pregnancy outcomes and on preterm infants' clinical and neurodevelopmental outcomes up to 2 years corrected age. This is a retrospective, cohort study led at a level IV Obstetric and Neonatal Unit in Bologna, Italy. Pregnant women were eligible if having singleton pregnancies, with no major foetal anomaly detected, and diagnosed with early FGR + AEDF (defined as FGR + AEDF detected before 32 weeks gestation). Early FGR + AEDF was further classified according to time of onset and specific features into very early and persistent (VEP, FGR + AEDF first detected at 20-24 weeks gestation and persistent at the following scans), very early but transient (VET, FGR + AEDF detected at 20-24 weeks gestation and progressively improving at the following scans) and later (LA, FGR + AEDF detected between 25 and 32 weeks gestation). Pregnancy and neonatal outcomes and infant follow-up data were collected and compared among groups. Neurodevelopment was assessed using the revised Griffiths Mental Developmental Scales (GMDS-R) 0-2 years. A regression analysis was performed to identify early predictors of preterm infants' neurodevelopmental impairment. Fifty-two pregnant women with an antenatal diagnosis of early FGR + AEDF were included in the study (16 VEP, 14 VET, 22 LA). Four intrauterine foetal deaths occurred, all in the VEP group (p = 0.010). Compared to LA infants, VEP infants were born with lower gestational age and lower birth weight, had lower arterial cord blood pH and were at higher risk for intraventricular haemorrhage and periventricular leukomalacia (p < 0.05 for all comparisons). At 12 months, VEP infants had worse GMDS-R scores, both in the general quotient (mean [SD] 91.8 [12.4] vs 104.6 [8.7] in LA) and in the performance domain (mean [SD] 93.3 [15.4] vs 108.8 [8.8] in LA). This latter difference persisted at 24 months (mean [SD] 68.3 [17.0] vs 92.9 [17.7] in LA). In multivariate analysis, at 12 months corrected age, PVL was found to be an independent predictor of impaired general quotient, while the features and timing of antenatal Doppler alterations predicted worse scores in the performance domain. Conclusion: Timing of onset and features of early FGR + AEDF might impact differently on neonatal clinical and neurodevelopmental outcomes. Shared awareness of the importance of FGR + AEDF features between obstetricians and neonatologists may offer valuable tools for antenatal counselling and for tailoring pregnancy management and neonatal follow-up in light of specific antenatal and neonatal risk factors. What is Known: • Foetal growth restriction (FGR), together with antenatal umbilical Doppler abnormalities, is known to affect maternal and neonatal outcomes. • Infants born preterm and growth-restricted face the highest risk for neurodevelopmental impairment, especially when FGR occurs early during pregnancy (early FGR, before 32 weeks gestation). What is New: • The timing of onset and features of FGR and antenatal umbilical Doppler abnormalities impact differently on maternal and neonatal outcomes; when FGR and Doppler abnormalities occur very early, at the limit of neonatal viability, and persist until delivery, infants face the highest risk for neurodevelopmental impairment. • Shared knowledge between obstetricians and neonatologists about timing of onset and features of FGR would provide a valuable tool for informed antenatal counselling in high-risk pregnancies.
Topics: Infant; Pregnancy; Female; Infant, Newborn; Humans; Fetal Growth Retardation; Infant, Premature; Cohort Studies; Retrospective Studies; Umbilical Arteries; Gestational Age; Ultrasonography, Prenatal
PubMed: 37490110
DOI: 10.1007/s00431-023-05104-y -
Frontiers in Psychology 2023Very and extremely preterm children have been found to show delays in the development of language in early years. In some investigations, however, a rigorous control of...
INTRODUCTION
Very and extremely preterm children have been found to show delays in the development of language in early years. In some investigations, however, a rigorous control of biomedical complications, such as Periventricular Leukomalacia (PVL), Intraventricular Hemorrhage (IVH) or Bronchopulmonary Dysplasia (BPD), does not always exist. For that reason, a confounding effect of low gestational age and biomedical complications may lead to erroneous conclusions about the effect of gestational age.
METHODS
In this investigation we compare language development [use of words, sentence complexity and mean length of the three longest utterances (MLU3)] of three groups of Chilean children at 24 months of age (corrected age for preterm children). The first group was composed of 42 healthy full-term children (Full term group: FT), the second group of 60 preterm children born below 32 gestational weeks without medical complications (low risk preterm group: LRPT), and the third group was composed of 64 children below 32 gestational weeks who had medical complications (High risk preterm group: HRPT). The three groups were similar in terms of gender distribution, maternal education, and socio-economic environment. The instrument used to assess language was the Communicative Development Inventories (CDI). In addition, the Ages and Stages Questionnaire-3 (ASQ-3) was also used to assess other developmental dimensions.
RESULTS
The results indicate that HRPT and LRPT children obtained significantly lower results than the FT group in the three language measures obtained through the CDI. No significant differences were observed between the HRPT and the LRPT groups, although the HRPT obtained the lowest results in the three CDI measures. The results obtained through the administration of the ASQ-3 confirm the delay of both preterm groups in communicative development when compared to the FT group. No significant differences between the FT and the PT groups were observed in gross motor, fine motor and problem solving dimensions of the ASQ-3. The LRPT group obtained results that were significantly higher than those of the FT group and the HRPT group in gross motor development.
DISCUSSION
These results seem to indicate that the area of language development is particularly influenced by very or extremely low gestational age.
PubMed: 37484104
DOI: 10.3389/fpsyg.2023.1163252 -
Clinical Nutrition (Edinburgh, Scotland) Aug 2023Gut immaturity leads to feeding difficulties in very preterm infants (<32 weeks gestation at birth). Maternal milk (MM) is the optimal diet but often absent or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Gut immaturity leads to feeding difficulties in very preterm infants (<32 weeks gestation at birth). Maternal milk (MM) is the optimal diet but often absent or insufficient. We hypothesized that bovine colostrum (BC), rich in protein and bioactive components, improves enteral feeding progression, relative to preterm formula (PF), when supplemented to MM. Aim of the study is to determine whether BC supplementation to MM during the first 14 days of life shortens the time to full enteral feeding (120 mL/kg/d, TFF120).
METHODS
This was a multicenter, randomized, controlled trial at seven hospitals in South China without access to human donor milk and with slow feeding progression. Infants were randomly assigned to receive BC or PF when MM was insufficient. Volume of BC was restricted by recommended protein intake (4-4.5 g/kg/d). Primary outcome was TFF120. Feeding intolerance, growth, morbidities and blood parameters were recorded to assess safety.
RESULTS
A total of 350 infants were recruited. BC supplementation had no effect on TFF120 in intention-to-treat analysis [n (BC) = 171, n (PF) = 179; adjusted hazard ratio, aHR: 0.82 (95% CI: 0.64, 1.06); P = 0.13]. Body growth and morbidities did not differ, but more cases of periventricular leukomalacia were detected in the infants fed BC (5/155 vs. 0/181, P = 0.06). Blood chemistry and hematology data were similar between the intervention groups.
CONCLUSIONS
BC supplementation during the first two weeks of life did not reduce TFF120 and had only marginal effects on clinical variables. Clinical effects of BC supplementation on very preterm infants in the first weeks of life may depend on feeding regimen and remaining milk diet.
TRIAL REGISTRATION
http://www.
CLINICALTRIALS
gov: NCT03085277.
Topics: Infant; Pregnancy; Female; Infant, Newborn; Humans; Animals; Cattle; Infant, Premature; Colostrum; Dietary Supplements; Milk, Human; Infant, Very Low Birth Weight; Infant, Premature, Diseases; Fetal Growth Retardation; Enterocolitis, Necrotizing
PubMed: 37437359
DOI: 10.1016/j.clnu.2023.06.024 -
Translational Pediatrics Jun 2023Narcotics and sedatives are widely used in neonatal intensive care units for very preterm infants. This study aimed to describe the current use of narcotics and/or...
BACKGROUND
Narcotics and sedatives are widely used in neonatal intensive care units for very preterm infants. This study aimed to describe the current use of narcotics and/or sedatives among very preterm infants in Chinese neonatal intensive care units, with an emphasis on infants on invasive mechanical ventilation, and to investigate the association of exposure to narcotics and/or sedatives with neonatal outcomes.
METHODS
This was a retrospective observational cohort study that enrolled all infants born at 24-31 weeks and admitted to 57 tertiary neonatal intensive care units in the Chinese Neonatal Network in 2019. A multivariate logistic regression model was used to assess the association between narcotics and/or sedatives exposure and major neonatal outcomes.
RESULTS
Among 9,442 very preterm infants enrolled, 1,566 (16.6%) received at least one dose of narcotics or sedatives, 111 (1.2%) received only narcotics, 1,301 (13.8%) received sedatives solely, and 154 (1.6%) received both narcotics and sedatives during their hospital stay. Of 4,172 very preterm infants who underwent invasive mechanical ventilation, 1,117 (26.8%) received at least one dose of narcotics or sedatives, with 883 (21.2%) only received sedatives. Significant site variation of narcotics/sedatives use existed among hospitals, with the application rate ranging from 0-72.5% in individual hospital. The narcotics and/or sedatives use by very preterm infants was independently associated with increased risks for periventricular leukomalacia, severe retinopathy of prematurity, and bronchopulmonary dysplasia.
CONCLUSIONS
Narcotic and/or sedative administration is relatively conservative for very preterm infants in Chinese neonatal intensive care units, with significant variation among hospitals. Since narcotic and sedative use might be related to adverse neonatal outcomes, a pressing and developing need for national quality improvement initiatives is seen with respect to pain/stress management for very preterm infants.
PubMed: 37427065
DOI: 10.21037/tp-22-672 -
International Journal of Molecular... Jun 2023Germinal matrix hemorrhage (GMH) is a pathology that occurs in infancy, with often devastating long-term consequences. Posthemorrhagic hydrocephalus (PHH) can develop...
Germinal matrix hemorrhage (GMH) is a pathology that occurs in infancy, with often devastating long-term consequences. Posthemorrhagic hydrocephalus (PHH) can develop acutely, while periventricular leukomalacia (PVL) is a chronic sequala. There are no pharmacological therapies to treat PHH and PVL. We investigated different aspects of the complement pathway in acute and chronic outcomes after murine neonatal GMH induced at postnatal day 4 (P4). Following GMH-induction, the cytolytic complement membrane attack complex (MAC) colocalized with infiltrating red blood cells (RBCs) acutely but not in animals treated with the complement inhibitor CR2-Crry. Acute MAC deposition on RBCs was associated with heme oxygenase-1 expression and heme and iron deposition, which was reduced with CR2-Crry treatment. Complement inhibition also reduced hydrocephalus and improved survival. Following GMH, there were structural alterations in specific brain regions linked to motor and cognitive functions, and these changes were ameliorated by CR2-Crry, as measured at various timepoints through P90. Astrocytosis was reduced in CR2-Crry-treated animals at chronic, but not acute, timepoints. At P90, myelin basic protein and LAMP-1 colocalized, indicating chronic ongoing phagocytosis of white matter, which was reduced by CR2-Crry treatment. Data indicate acute MAC-mediated iron-related toxicity and inflammation exacerbated the chronic effects of GMH.
Topics: Mice; Animals; Hydrocephalus; Complement System Proteins; Cerebral Hemorrhage; Inflammation; Complement Membrane Attack Complex; Iron; Recombinant Fusion Proteins
PubMed: 37373319
DOI: 10.3390/ijms241210171 -
The Cochrane Database of Systematic... Jun 2023Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015.
OBJECTIVES
To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We also searched the reference lists of identified clinical trials and handsearched conference abstracts. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs assessing the efficacy of PTX with antibiotics (any dose or duration) for treatment of suspected or confirmed sepsis or NEC in neonates. We included three comparisons: (1) PTX with antibiotics compared to placebo or no intervention with antibiotics; (2) PTX with antibiotics compared to PTX with antibiotics and adjunct treatments such as immunoglobulin M-enriched intravenous immunoglobulin (IgM-enriched IVIG); (3) PTX with antibiotics compared to adjunct treatments such as IgM-enriched IVIG with antibiotics.
DATA COLLECTION AND ANALYSIS
We reported typical risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes derived from a fixed-effect model of meta-analysis. We calculated the number needed to treat for an additional beneficial outcome (NNTB) if there was a statistically significant reduction in RD.
MAIN RESULTS
We identified no new studies for this update. We included six RCTs (416 neonates). All of the included studies examined neonates with sepsis; we identified no studies on neonates with NEC. Four of the six trials had high risk of bias for at least one risk of bias domain. Comparison 1: PTX with antibiotics compared to placebo with antibiotics, or antibiotics alone, in neonates with sepsis may reduce all-cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35 to 0.93; typical RD -0.08, 95% CI -0.14 to -0.01; NNTB 13, 95% CI 7 to 100; 6 studies, 416 participants, low-certainty evidence) and may decrease length of hospital stay (LOS) (MD -7.74, 95% CI -11.72 to -3.76; 2 studies, 157 participants, low-certainty evidence). The evidence is very uncertain that PTX with antibiotics compared to placebo or no intervention results in any change in chronic lung disease (CLD) (RR 1.50, 95% CI 0.45 to 5.05; 1 study, 120 participants, very low-certainty evidence), severe intraventricular haemorrhage (sIVH) (RR 0.75, 95% CI 0.28 to 2.03; 1 study, 120 participants, very low-certainty evidence), periventricular leukomalacia (PVL) (RR 0.50, 95% CI 0.10 to 2.63; 1 study, 120 participants, very low-certainty evidence), NEC (RR 0.56, 95% CI 0.29 to 1.06; 6 studies, 405 participants, very low-certainty evidence), or retinopathy of prematurity (ROP) (RR 0.40, 95% CI 0.08 to 1.98; 1 study, 120 participants, very low-certainty evidence) in neonates with sepsis. Comparison 2: the evidence is very uncertain that PTX with antibiotics compared to PTX with antibiotics and IgM-enriched IVIG has any effect on mortality (RR 0.71, 95% CI 0.24 to 2.10; 102 participants, 1 study, very low-certainty evidence) or development of NEC in neonates with sepsis (RR 1.33, 95% CI 0.31 to 5.66; 1 study, 102 participants, very low-certainty evidence). The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported. Comparison 3: the evidence is very uncertain that PTX with antibiotics compared to IgM-enriched IVIG with antibiotics has any effect on mortality (RR 1.25, 95% CI 0.36 to 4.39; 102 participants, 1 study, very low-certainty evidence) or development of NEC (RR 1.33, 95% CI 0.31 to 5.66; 102 participants, 1 study, very low-certainty evidence) in neonates with sepsis. The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported. All of the included studies evaluated adverse effects due to PTX, but none were reported in the intervention group in any of the comparisons.
AUTHORS' CONCLUSIONS
Low-certainty evidence suggests that adjunct PTX therapy in neonatal sepsis may decrease mortality and length of hospital stay without any adverse effects. The evidence is very uncertain if PTX with antibiotics compared to PTX with antibiotics and IgM-enriched IVIG, or PTX with antibiotics compared to IgM-enriched IVIG with antibiotics, has any effect on mortality or development of NEC. We encourage researchers to undertake well-designed multicentre trials to confirm or refute the effectiveness and safety of pentoxifylline in reducing mortality and morbidity in neonates with sepsis or NEC.
Topics: Humans; Infant, Newborn; Anti-Bacterial Agents; Enterocolitis, Necrotizing; Immunoglobulin M; Immunoglobulins, Intravenous; Infant, Premature; Lung Diseases; Neonatal Sepsis; Pentoxifylline; Retinopathy of Prematurity; Sepsis
PubMed: 37338074
DOI: 10.1002/14651858.CD004205.pub4 -
Journal of Neuroinflammation Jun 2023Germinal matrix hemorrhage is a devastating disease of pre-term infancy commonly resulting in post-hemorrhagic hydrocephalus, periventricular leukomalacia, and...
BACKGROUND
Germinal matrix hemorrhage is a devastating disease of pre-term infancy commonly resulting in post-hemorrhagic hydrocephalus, periventricular leukomalacia, and subsequent neurocognitive deficits. We demonstrate vascular expression of the adhesion molecule P-selectin after GMH and investigate a strategy to specifically target complement inhibition to sites of P-selectin expression to mitigate the pathological sequelae of GMH.
METHODS
We prepared two fusion proteins consisting of different anti-P-selectin single chain antibodies (scFv's) linked to the complement inhibitor Crry. One scFv targeting vehicle (2.12scFv) blocked the binding of P-selectin to its PSGL-1 ligand expressed on leukocytes, whereas the other targeting vehicle (2.3scFv) bound P-selectin without blocking ligand binding. Post-natal C57BL/6 J mice on day 4 (P4) were subjected to collagenase induced-intraventricular hemorrhage and treated with 2.3Psel-Crry, 2.12Psel-Crry, or vehicle.
RESULTS
Compared to vehicle treatment, 2.3Psel-Crry treatment after induction of GMH resulted in reduced lesion size and mortality, reduced hydrocephalus development, and improved neurological deficit measurements in adolescence. In contrast, 2.12Psel-Crry treatment resulted in worse outcomes compared to vehicle. Improved outcomes with 2.3Psel-Crry were accompanied by decreased P-selectin expression, and decreased complement activation and microgliosis. Microglia from 2.3Psel-Crry treated mice displayed a ramified morphology, similar to naïve mice, whereas microglia in vehicle treated animals displayed a more ameboid morphology that is associated with a more activated status. Consistent with these morphological characteristics, there was increased microglial internalization of complement deposits in vehicle compared to 2.3Psel-Crry treated animals, reminiscent of aberrant C3-dependent microglial phagocytosis that occurs in other (adult) types of brain injury. In addition, following systemic injection, 2.3Psel-Crry specifically targeted to the post-GMH brain. Likely accounting for the unexpected finding that 2.12Psel-Crry worsens outcome following GMH was the finding that this construct interfered with coagulation in this hemorrhagic condition, and specifically with heterotypic platelet-leukocyte aggregation, which express P-selectin and PSGL-1, respectively.
CONCLUSIONS
GMH induces expression of P-selectin, the targeting of which with a complement inhibitor protects against pathogenic sequelae of GMH. A dual functioning construct with both P-selectin and complement blocking activity interferes with coagulation and worsens outcomes following GMH, but has potential for treatment of conditions that incorporate pathological thrombotic events, such as ischemic stroke.
Topics: Animals; Mice; Cerebral Hemorrhage; Complement Inactivating Agents; Complement System Proteins; Hydrocephalus; Ligands; Mice, Inbred C57BL; P-Selectin
PubMed: 37322469
DOI: 10.1186/s12974-023-02828-4 -
Neurobiology of Disease Aug 2023Oligodendrocytes (OLs), the myelin-forming cells of the central nervous system, are integral to axonal integrity and function. Hypoxia-ischemia episodes can cause severe... (Review)
Review
Oligodendrocytes (OLs), the myelin-forming cells of the central nervous system, are integral to axonal integrity and function. Hypoxia-ischemia episodes can cause severe damage to these vulnerable cells through excitotoxicity, oxidative stress, inflammation, and mitochondrial dysfunction, leading to axonal dystrophy, neuronal dysfunction, and neurological impairments. OLs damage can result in demyelination and myelination disorders, severely impacting axonal function, structure, metabolism, and survival. Adult-onset stroke, periventricular leukomalacia, and post-stroke cognitive impairment primarily target OLs, making them a critical therapeutic target. Therapeutic strategies targeting OLs, myelin, and their receptors should be given more emphasis to attenuate ischemia injury and establish functional recovery after stroke. This review summarizes recent advances on the function of OLs in ischemic injury, as well as the present and emerging principles that serve as the foundation for protective strategies against OLs deaths.
Topics: Humans; Ischemic Stroke; Oligodendroglia; Myelin Sheath; Central Nervous System; Stroke
PubMed: 37321419
DOI: 10.1016/j.nbd.2023.106200