Celecoxib treatment alleviates cerebral injury in a rat model of post-traumatic epilepsy.

Background: An important factor contributing to the development and occurrence of post-traumatic epilepsy (PTE) is neuroinflammation and oxidative stress. The effects of celecoxib include inhibiting inflammatory reactions and antioxidant stress and reducing seizures, making it a potential epilepsy treatment solution. Objective: To observe the effect of celecoxib on early epilepsy in post-traumatic epilepsy rats. Methods: Twenty-four adult healthy male Sprague-Dawley rats were randomly assigned to three groups: sham-operated, PTE, and celecoxib. A rat model of PTE was established by injecting ferrous chloride into the right frontal cortex. Afterward, the behavior of rats was observed and recorded. 3.0T superconducting magnetic resonance imaging (MRI) was used to describe the changes in ADC values of the brain. HE and Nissl staining were also used to detect the damage to frontal lobe neurons. Furthermore, the expression of COX-2 protein in the right frontal lobe was detected by Western blot. Moreover, the contents of IL-1 and TNF-α in the right frontal lobe were detected by enzyme-linked immunosorbent assay. Results: Compared with the PTE group, the degree of seizures in rats treated with celecoxib declined dramatically (P < 0.05). Celecoxib-treated rats had significant decreases in tissue structural damage and cell death in the brain. The results of the MRI showed that celecoxib reduced the peripheral edema zone and ADC value of the cortex around the damaged area of the right frontal lobe in the celecoxib-treatment group, which was significantly decreased compared with the PTE group (P < 0.05). Furthermore, celecoxib decreased the expression of COX-2, IL-1ß, and TNF-α in brain tissue (P < 0.05). Conclusions: In PTE rats, celecoxib significantly reduced brain damage and effectively reduced seizures. As a result of celecoxib's ability to inhibit inflammation, it can reduce the edema caused by injury in rat brain tissue.

The Current Knowledge of Cerebral Magnetic Resonance Imaging in Monochorionic Twins: A Systematic Review of the Last 20 Years.

The distinct placental angioarchitecture in monochorionic (MC) pregnancies increases the risk of complications such as twin-twin transfusion syndrome (TTTS), twin anemia polycythemia sequence (TAPS), and selective fetal growth restriction (sFGR). The aim of this systematic review was to evaluate the incidence, type, and severity of cerebral injury and structural brain development on fetal and/or neonatal cerebral magnetic resonance imaging (MRI) in MC twins with or without complications. Twenty-three studies were included, covering a wide range of complications observed during MC pregnancies, with studies involving sIUFD (n = 12), TTTS (n = 7), mixed complications (n = 2), TAPS (n = 1), and uncomplicated MC pregnancy (n = 1). TAPS and sFGR were largely underrepresented in the current literature. The included studies reported that MC pregnancies with single intrauterine fetal demise (sIUFD) are most at risk for cerebral injury during the fetal period. The overall median incidence of cerebral injury after sIUFD was 28.3% (0-55%). Severe antenatal cerebral injury after sIUFD was detected antenatally in 6.5% (0-36%) of the cases. Three of the included studies described the incidence, type, and severity of cerebral injury on neonatal MRI in MC twins. Structural brain development based on cerebral biometry was only assessed in two studies, revealing significantly smaller biometric measurements of the cerebrum in cases of single sIUFD or smaller twins compared to singleton pregnancies. To enhance our understanding of the potential risks and pathophysiological mechanisms associated with cerebral injury and structural brain development in MC twins, there is a need for future studies and standardized protocols using serial fetal and neonatal MRI imaging in addition to routine ultrasound imaging.

Mouse models of cerebral injury and cognitive impairment in hypertension.

Hypertension is a major risk factor for dementia, including both vascular and neurodegenerative etiologies. With the original aim of studying the effect of blood pressure elevation on canonical target organs of hypertension as the heart, the vasculature or the kidneys, several experimental models of hypertension have sprouted during the years. With the more recent interest of understanding the cerebral injury burden caused by hypertension, it is worth understanding how the main models of hypertension or localized cerebral hypertension stand in the field of hypertension-induced cerebral injury and cognitive impairment. With this review we will report main genetic, pharmacological and surgical models of cognitive impairment induced by hypertension, summarizing how each specific category and model can improve our understanding of the complex phenomenon of cognitive loss of vascular etiology.

LncRNA XIST Exacerbates Oxygen-Glucose Deprivation/Reoxygenation-Induced Cerebral Injury Through the miR-25-3p/TRAF3 Axis.

Ischemic stroke causes lethal damage to the brain. Identifying key regulators of OGD/R-induced cerebral injury is important for developing novel therapies for ischemic stroke. HMC3 and SH-SY5Y cells were treated with OGD/R as an in vitro ischemic stroke model. Cell viability and apoptosis were determined via CCK-8 assay and flow cytometry. Inflammatory cytokines were examined by ELISA. Luciferase activity was measured for evaluating the interaction of XIST, miR-25-3p, and TRAF3. Bcl-2, Bax, Bad, cleaved-caspase 3, total caspase 3, and TRAF3 were detected via western blotting. HMC3 and SH-SY5Y cells showed increased XIST expression and decreased miR-25-3p expression following OGD/R. Importantly, silencing of XIST and overexpression of miR-25-3p reduced apoptosis and inflammatory response following OGD/R. Furthermore, XIST worked as a miR-25-3p sponge, and miR-25-3p targeted TRAF3 to suppress its expression. Moreover, the knockdown of TRAF3 ameliorated OGD/R-induced injury. Loss of XIST-mediated protective effects was reversed by overexpression of TRAF3. LncRNA XIST exacerbates OGD/R-induced cerebral damage via sponging miR-25-3p and enhancing TRAF3 expression.

Single fetal demise in monochorionic twins: How to predict cerebral injury in the survivor co-twin?

INTRODUCTION: The aims of the study were to evaluate perinatal outcome in monochorionic (MC) twins complicated with single intrauterine fetal death, spontaneously vs after fetal therapy, and to assess antenatal events that increase the risk of cerebral injury. MATERIAL AND METHODS: Historical cohort study of MC pregnancies with single intrauterine fetal death diagnosed or referred to a tertiary referral hospital (2012-2020). Adverse perinatal outcome included termination of pregnancy, perinatal death, abnormal fetal or neonatal neuroimaging and abnormal neurological development. RESULTS: A total of 68 MC pregnancies with single intrauterine fetal death after 14 weeks of gestation were included. Sixty-five (95.6%) occurred in complicated MC pregnancies (twin to twin transfusion syndrome: 35/68 [51.5%]; discordant malformation: 13/68 [19.1%], selective intrauterine growth restriction: 10/68 [14.7%], twin reversed arterial perfusion sequence: 5/68 [7.3%] and cord entanglement in monoamniotic twins: 2/68 [2.94%]). In 52 cases (76.5%) single intrauterine fetal demise occurred after fetal therapy and in 16 (23.5%) occurred spontaneously. Cerebral damage included 14/68 cases (20.6%): 6/68 cases (8.82%) were prenatal lesions and 8/68 cases (11.8%) were postnatal. Risk of cerebral damage tended to be higher in the spontaneous death group (6/16, 37.5%) compared to the therapy-group (8/52, 15.38%) (p = 0.07). The risk increased with gestational age at intrauterine death (OR 1.21, 95% CI: 1.04-1.41, p = 0.014) and was higher in those surviving co-twins who developed anemia (OR 9.27, 95% CI: 1.50-57.12, p = 0.016). Pregnancies complicated with selective intrauterine growth restriction tended to be at higher risk for neurological damage (OR 2.85, 95% CI: 0.68-11.85, p = 0.15). Preterm birth rate (<37 weeks of pregnancy) was 61.7% (37/60). Seven of eight postnatal cerebral lesions (87.5%) were related to extreme prematurity. Overall perinatal survival rate was 88.3% (57/68) and 7% (4/57) of children had an abnormal neurological outcome. CONCLUSIONS: Risk of cerebral damage in single intrauterine fetal death is especially high when it occurs spontaneously. Gestational age at single intrauterine fetal death, selective intrauterine growth restriction and anemia of the surviving co-twin are the main predictors for prenatal lesions and might be useful in parent counseling. Abnormal postnatal neurological outcome is closely related to extreme prematurity.

Current recommendations for management of paediatric diabetic ketoacidosis.

Treatment of paediatric diabetic ketoacidosis (DKA) includes careful attention to fluids and electrolytes to minimize the risk of complications such as cerebral injury (CI), which is associated with high morbidity and mortality. The incidence of cerebral edema in paediatric DKA has not decreased despite the use of fluid-limiting protocols based on restricting early fluid resuscitation. New evidence suggests that early isotonic fluid therapy does not confer additional risk and may improve outcomes in some patients. Protocols and clinical practice guidelines are being adjusted, with a particular focus on recommendations for initial and ongoing fluids and electrolyte monitoring and replacement. Initial isotonic fluid resuscitation is now recommended for all patients in the first 20 to 30 minutes after presentation, followed by repletion of volume deficit over 36 hours in association with an insulin infusion, electrolyte supplementation, and careful monitoring for and management of potential CI.

M2 macrophages mediate fibrotic scar formation in the early stages after cerebral ischemia in rats.

In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly understood. M2 macrophages regulate fibrotic scar formation after injury to the heart, lung, kidney, and central nervous system. However, it remains to be clarified whether and how M2 macrophages regulate fibrotic scar formation after cerebral ischemia injury. In this study, we found that, in a rat model of cerebral ischemia induced by middle cerebral artery occlusion/reperfusion, fibrosis and macrophage infiltration were apparent in the ischemic core in the early stage of injury (within 14 days of injury). The number of infiltrated macrophages was positively correlated with fibronectin expression. Depletion of circulating monocyte-derived macrophages attenuated fibrotic scar formation. Interleukin 4 (IL4) expression was strongly enhanced in the ischemic cerebral tissues, and IL4-induced M2 macrophage polarization promoted fibrotic scar formation in the ischemic core. In addition, macrophage-conditioned medium directly promoted fibroblast proliferation and the production of extracellular matrix proteins in vitro. Further pharmacological and genetic analyses showed that sonic hedgehog secreted by M2 macrophages promoted fibrogenesis in vitro and in vivo, and that this process was mediated by secretion of the key fibrosis-associated regulatory proteins transforming growth factor beta 1 and matrix metalloproteinase 9. Furthermore, IL4-afforded functional restoration on angiogenesis, cell apoptosis, and infarct volume in the ischemic core of cerebral ischemia rats were markedly impaired by treatment with an sonic hedgehog signaling inhibitor, paralleling the extent of fibrosis. Taken together, our findings show that IL4/sonic hedgehog/transforming growth factor beta 1 signaling targeting macrophages regulates the formation of fibrotic scar and is a potential therapeutic target for ischemic stroke.

Transcriptomic Profiling of circRNAs in rat Hippocampus after Deep Hypothermic Circulatory Arrest.

Neurologic abnormalities occurring after deep hypothermic circulatory arrest (DHCA) remain a significant concern. However, molecular mechanisms leading to DHCA-related cerebral injury are still ill-defined. Circular RNAs (circRNAs) are a class of covalently closed non-coding RNAs and can play important roles in different types of cerebral injury. This study aimed to investigate circRNAs expression profiles in rat hippocampus after DHCA and explore the potential functions of circRNAs in DHCA-related cerebral injury. Hence, the DHCA procedure in rats was established and a transcriptomic profiling of circRNAs in rat hippocampus was done. As a result, a total of 35192 circRNAs were identified. Among them, 339 circRNAs were dysregulated, including 194 down-regulated and 145 up-regulated between DHCA and sham group. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed based on the host genes of all dysregulated circRNAs. Also, 4 circRNAs were validated by RT-qPCR (rno_circ_0028462, rno_circ_0037165, rno_circ_0045161 and rno_circ_0019047). Then a circRNA-microRNA (miRNA) interaction network involving 4 candidate circRNAs was constructed. Furthermore, functional enrichment analysis of the miRNA-targeting mRNAs of every candidate circRNA was conducted to gain insight into each of the 4 circRNAs. Our study provided a better understanding of circRNAs in the mechanisms of DHCA-related cerebral injury and some potential targets for neuroprotection.

The Protective Effect of Vitexin Compound B-1 on Rat Cerebral I/R Injury through a Mechanism Involving Modulation of miR-92b/NOX4 Pathway.

BACKGROUND: Recent studies have uncovered that vitexin compound B-1 (VB-1) can protect neurons against hypoxia/reoxygenation (H/R)-induced oxidative injury through suppressing NOX4 expression. OBJECTIVE: The aims of this study are to investigate whether VB-1 can protect the rat brain against ischemia/ reperfusion (I/R) injury and whether its effect on NOX4 expression is related to modulation of certain miRNAs expression. METHODS: Rats were subjected to 2 h of cerebral ischemia followed by 24 h of reperfusion to establish an I/R injury model, which showed an increase in neurological deficit score and infarct volume concomitant with an upregulation of NOX4 expression, increase in NOX activity, and downregulation of miR-92b. RESULTS: Administration of VB-1 reduced I/R cerebral injury accompanied by a reverse in NOX4 and miR-92b expression. Similar results were achieved in a neuron H/R injury model. Next, we evaluated the association of miR-92b with NOX4 by its mimics in the H/R model. H/R treatment increased neurons apoptosis concomitant with an upregulation of NOX4 and NOX activity while downregulation of miR-92b. All these effects were reversed in the presence of miR-92b mimics, confirming the function of miR-92b in suppressing NOX4 expression. CONCLUSION: We conclude the protective effect of VB-1 against rat cerebral I/R injury through a mechanism involving modulation of miR-92b/NOX4 pathway.

The monoacylglycerol lipase inhibitor, JZL184, has comparable effects to therapeutic hypothermia, attenuating global cerebral injury in a rat model of cardiac arrest.

Post-resuscitation cerebral ischemia-reperfusion injury (IRI) is a vital contributor to poor neurological prognosis. Exploring novel therapeutics that attenuate cerebral IRI is of great significance. Inflammation plays a role in the development of cerebral IRI after successful cardiopulmonary resuscitation (CPR). Monoacylglycerol lipase (MAGL) is an enzyme that is predominantly responsible for the metabolism of endocannabinoid 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA) metabolites, which are associated with inflammation. Therefore, we investigated the efficacy of the MAGL inhibitor, JZL184, on cerebral IRI and further compared the effects to therapeutic hypothermia (TH). Thirty-six rats were randomized into three groups: 1) JZL184; 2) Control; 3) TH (N = 12 for each group). Animals underwent 6 min of ventricular fibrillation (VF) followed with 8 min of CPR. After return of spontaneous circulation (ROSC), rats received an intraperitoneal injection of JZL184 (16 mg/kg) or DMSO (20 mg/ml) or body cooling was initiated. Cerebral microcirculation, brain edema, blood brain barrier (BBB) permeability, serum neuron-specific enolase (NSE), S-100ß, interleukin-6 (IL-6) and interleukin-10 (IL-10) were quantified at 6 h post ROSC. Compared to control, treatment with JZL184 or TH was associated with significantly ameliorated cerebral microcirculation, mitigated brain edema, attenuated BBB permeability, decreased serum levels of NSE, S-100ß and IL-6, and increased serum IL-10 levels (p < 0.05). There was no significant difference in the above measurements between JZL184 and TH. JZL184 has comparable neuroprotective effects to therapeutic hypothermia on global cerebral IRI in a rat model of cardiac arrest (CA).

High-resolution perioperative cerebral blood flow autoregulation measurement: a practical and feasible approach for widespread clinical monitoring.

A growing body of evidence demonstrates that excursions of BP below or above the limits of cerebral blood flow autoregulation are associated with complications in patients with neurological injury or for those undergoing cardiac surgery. Moreover, recent evidence suggests that maintaining MAP above the lower limit of cerebral autoregulation during cardiopulmonary bypass reduces the frequency of postoperative delirium and is associated with improved memory 1 month after surgery. Continuous measurement of BP in relation to cerebral autoregulation limits using a virtual patient monitoring platform processing near-infrared spectroscopy digital signals offers the hope of bringing this application to the bedside.

Inhibition of progesterone receptor membrane component-1 exacerbates neonatal hypoxic-ischemic cerebral damage in male mice.

This study investigated the expression of progesterone receptor membrane component 1 (pgrmc1) in the brains of male and female mice, and the effect of inhibiting pgrmc1 on neonatal hypoxic-ischemic (HI) cerebral injury in male mice. A mouse model of neonatal HI brain injury was established, and AG205, a specific antagonist of pgrmc1, was injected into the left lateral cerebral ventricle 1 h before HI. Histological staining, behavior testing, Western blots, and quantitative PCR (qPCR) were employed to evaluate pgrmc1 expression, brain damage, neurological function, and molecular mechanisms. Results demonstrated that the mRNA and protein levels of pgrmc1 increased significantly in the cortex and hippocampus 72 h after HI without sex differences. The inhibition of pgrmc1 exacerbated the neonatal brain damage in the acute stage of HI in male mice as seen in the increase in brain water content, infarction area, and neuronal death. Inhibition of pgrmc1 also aggravated the neurological dysfunction and anxiety induced by HI brain injury. In addition, inhibition of pgrmc1 activated the NF-kB signaling and NF-κB-mediated cytokines, and inhibited BDNF/PI3K/AKT pathway in the brains of the newborn HI mice. The results indicated that pgrmc1 inhibition exacerbated the brain damage in newborn male mice subjected to HI by activating IκBα/NFκB signaling and inhibiting BDNF/PI3K/Akt pathway.

Biomarkers of Cerebral Injury for Prediction of Postoperative Cognitive Dysfunction in Patients Undergoing Cardiac Surgery.

OBJECTIVES: To assess the ability of the biomarkers neuron-specific enolase (NSE), tau, neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP) to predict postoperative cognitive dysfunction (POCD) at discharge in patients who underwent cardiac surgery. DESIGN: Post hoc analyses (with tests being prespecified before data analyses) from a randomized clinical trial. SETTING: Single-center study from a primary heart center in Denmark. PARTICIPANTS: Adult patients undergoing elective or subacute on-pump coronary artery bypass grafting and/or aortic valve replacement. INTERVENTIONS: Blood was collected before induction of anesthesia, after 24 hours, after 48 hours, and at discharge from the surgical ward. The International Study of Postoperative Cognitive Dysfunction test battery was applied to diagnose POCD at discharge and after three months. Linear mixed models of covariance were used to assess whether repeated measurements of biomarker levels were associated with POCD. Receiver operating characteristic (ROC) curves were applied to assess the predictive value of each biomarker measurement for POCD. MEASUREMENTS AND MAIN RESULTS: A total of 168 patients had biomarkers measured at baseline, and 47 (28%) fulfilled the POCD criteria at discharge. Patients with POCD at discharge had significantly higher levels of tau (p = 0.02) and GFAP (p = 0.01) from baseline to discharge. The biomarker measurements achieving the highest area under the ROC curve for prediction of POCD at discharge were NFL measured at discharge (AUC, 0.64; 95% confidence interval [CI], 0.54-0.73), GFAP measured 48 hours after induction (AUC, 0.64; 95% CI, 0.55-0.73), and GFAP measured at discharge (AUC, 0.64; 95% CI, 0.54-0.74), corresponding to a moderate predictive ability. CONCLUSIONS: Postoperative serum levels of tau and GFAP were significantly elevated in cardiac surgery patients with POCD at discharge, however, the biomarkers achieved only modest predictive abilities for POCD at discharge. Postoperative levels of NSE were not associated with POCD at discharge.

Early Post-ischemic Brain Glucose Metabolism Is Dependent on Function of TLR2: a Study Using [18F]F-FDG PET-CT in a Mouse Model of Cardiac Arrest and Cardiopulmonary Resuscitation.

PURPOSE: The mammalian brain glucose metabolism is tightly and sensitively regulated. An ischemic brain injury caused by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) affects cerebral function and presumably also glucose metabolism. The majority of patients who survive CA suffer from cognitive deficits and physical disabilities. Toll-like receptor 2 (TLR2) plays a crucial role in inflammatory response in ischemia and reperfusion (I/R). Since deficiency of TLR2 was associated with increased survival after CA-CPR, in this study, glucose metabolism was measured using non-invasive [18F]F-FDG PET-CT imaging before and early after CA-CPR in a mouse model comparing wild-type (WT) and TLR2-deficient (TLR2-/-) mice. The investigation will evaluate whether FDG-PET could be useful as an additional methodology in assessing prognosis. PROCEDURES: Two PET-CT scans using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]F-FDG) tracer were carried out to measure dynamic glucose metabolism before and early after CPR. To achieve this, anesthetized and ventilated adult female WT and TLR2-/- mice were scanned in PET-CT. After recovery from the baseline scan, the same animals underwent 10-min KCL-induced CA followed by CPR. Approximately 90 min after CA, measurements of [18F]F-FDG uptake for 60 min were started. The [18F]F-FDG standardized uptake values (SUVs) were calculated using PMOD-Software on fused FDG-PET-CT images with the included 3D Mirrione-Mouse-Brain-Atlas. RESULTS: The absolute SUVmean of glucose in the whole brain of WT mice was increased about 25.6% after CA-CPR. In contrast, the absolute glucose SUV in the whole brain of TLR2-/- mice was not significantly different between baseline and measurements post CA-CPR. In comparison, baseline measurements of both mouse strains show a highly significant difference with regard to the absolute glucose SUV in the whole brain. Values of TLR2-/- mice revealed a 34.6% higher glucose uptake. CONCLUSIONS: The altered mouse strains presented a different pattern in glucose uptake under normal and ischemic conditions, whereby the post-ischemic differences in glucose metabolism were associated with the function of key immune factor TLR2. There is evidence for using early FDG-PET-CT as an additional diagnostic tool after resuscitation. Further studies are needed to use PET-CT in predicting neurological outcomes.

Early imaging predictors of fetal cerebral ischemic injury in monochorionic twin pregnancy complicated by spontaneous single intrauterine death.

OBJECTIVE: Monochorionic twin pregnancies are at increased risk of single intrauterine death (sIUD) and subsequent brain injury in the surviving twin owing to shared placentation. We assessed the association between middle cerebral artery peak systolic velocity (MCA-PSV) and cerebral injury on magnetic resonance imaging (MRI) and examined the association between cerebral findings on diffusion-weighted imaging (DWI) and those on T2-weighted imaging following spontaneous sIUD. METHODS: This was a retrospective cohort study of monochorionic pregnancies complicated by spontaneous sIUD followed at a tertiary center between January 2008 and January 2020. Pregnancies with sIUD following laser treatment, those with selective feticide, double IUD occurring on the same day or sIUD before 14 weeks' gestation were excluded, as were cases in which MCA-PSV was not measured or DWI-MRI was not performed. The ability of MCA-PSV Doppler to predict subsequent cerebral injury on MRI was assessed, and DWI findings were analyzed and compared with those on susceptibility-weighted imaging (SWI) and T2-weighted MRI to determine its diagnostic accuracy. RESULTS: We assessed 64 monochorionic pregnancies complicated by spontaneous sIUD. Of these, 47 (73.4%) pregnancies underwent fetal brain MRI and met the inclusion criteria. Sixteen (34.0%) of these fetuses demonstrated cerebral injury on MRI. The median interval between the diagnosis of sIUD and MRI examination was 5 days. Fetuses with increased MCA-PSV > 1.5 multiples of the median (MoM) following sIUD were significantly more likely to demonstrate cerebral injury on MRI than were those with normal MCA-PSV (68.8% vs 38.7%; P = 0.05). The sensitivity and specificity of MCA-PSV > 1.5 MoM for predicting cerebral injury on MRI were 68.8% (95% CI, 41.3-88.9%) and 61.3% (95% CI, 42.2-78.2%), respectively. Patterns of early cerebral injury on T2-weighted and SWI-MRI included acute or subacute tissue swelling (n = 6), parenchymal atrophy (n = 7), loss of cortical ribbon (n = 1) and hemorrhage (n = 8). Early MRI within approximately 2 weeks after the diagnosis of sIUD demonstrated abnormal DWI along with coexisting SWI and T2-weighted sequelae in 56.3% (9/16) of cases. When DWI was normal and a second MRI examination was performed later (n = 7), there were no ischemic changes evident on T2-weighted imaging. CONCLUSIONS: Increased MCA-PSV is associated with, but predicts poorly, cerebral injury after sIUD. Early MRI with DWI within approximately 2 weeks after the diagnosis of sIUD is valuable in identifying any cerebral injury. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Mesenchymal Stem Cells Alleviate Post-resuscitation Cardiac and Cerebral Injuries by Inhibiting Cell Pyroptosis and Ferroptosis in a Swine Model of Cardiac Arrest.

Following cardiopulmonary resuscitation (CPR), the ensuing cardiac and cerebral injuries contribute to the poor outcome of cardiac arrest (CA) victims, in which the pathogenetic process is possibly driven by cell pyroptosis and ferroptosis. Mesenchymal stem cells (MSCs) have been shown to be a promising strategy for post-resuscitation cardiac and cerebral protection in rat, but its effectiveness in the clinically relevant swine model and the potential protective mechanism remain unknown. The present study was designed to investigate whether MSCs administration could alleviate post-resuscitation cardiac and cerebral injuries through the inhibition of cell pyroptosis and ferroptosis in swine. Twenty-four male domestic swine were randomly divided into three groups: sham, CPR, and MSC. A dose of 2.5×106/kg of MSCs derived from human embryonic stem cells was intravenously infused at 1.5, and 3 days prior to CA. The animal model was established by 8 min of CA and then 8 min of CPR. After resuscitation, cardiac, cerebral function and injury biomarkers were regularly evaluated for a total of 24 h. At 24 h post-resuscitation, pyroptosis-related proteins (NLRP3, ASC, cleaved caspase-1, GSDMD), proinflammatory cytokines (IL-1ß, IL-18), ferroptosis-related proteins (ACSL4, GPX4) and iron deposition in the heart, cortex and hippocampus were measured. Consequently, significantly greater cardiac, cerebral dysfunction and injuries after resuscitation were observed in the CPR and MSC groups compared with the sham group. However, the severity of cardiac and cerebral damage were significantly milder in the MSC group than in the CPR group. In addition, the expression levels of NLRP3, ASC, cleaved caspase-1, GSDMD and ACSL4, the contents of IL-1ß and IL-18, and the level of iron deposition were significantly higher while the expression level of GPX4 was significantly lower in the heart, cortex and hippocampus in all resuscitated animals compared with the sham group. Nevertheless, MSCs administration significantly decreased post-resuscitation cardiac, cerebral pyroptosis and ferroptosis compared to the CPR group. Our results showed that the administration of MSCs significantly alleviated post-resuscitation cardiac and cerebral injuries in swine, in which the protective effects were related to the inhibition of cell pyroptosis and ferroptosis.

Ileal atresia and severe cerebral injury after fetoscopic laser photocoagulation treatment for twin-to-twin transfusion syndrome.

BACKGROUND: Twin-to-twin transfusion syndrome (TTTS) is a significant cause of perinatal morbidity and mortality. Fetoscopic laser photocoagulation (FLP) is the optimal treatment option for twin-to-twin transfusion syndrome; but can cause central nervous system, extremity and intestinal system injury. CASE: We report the case report of ileal atresia and severe cerebral infarction co-occurrence after fetoscopic laser photocoagulation treatment. It is uncertain as to whether ileal atresia occurred due to ischemia associated with TTTS, the treatment with FLP, or a combination of both. CONCLUSIONS: Cases with prenatal ultrasonographic abnormalities after FLP should have a close assessment to detect bowel complications. Despite many developments in its management, TTTS remains an important risk factor for cerebral injury.

Asymptomatic Hyperinsulinemic Hypoglycemia and Grade 4 Intraventricular Hemorrhage in a Late Preterm Infant.

Hyperinsulinemic hypoglycemia (HH) has the potential to cause acute neurologic dysfunction and neurodevelopmental impairment. Parieto-occipital neuronal injuries have been reported in hypoglycemic infants, but intraparenchymal hemorrhage is rare. On day 5 of life, a late preterm infant was transferred to our care with recurrent asymptomatic hypoglycemia. Prior to arrival, plasma glucose levels were at a median of 1.25 mmol/L (22.5 mg/dL) in the first 6 hours of life, and he required a glucose infusion rate (GIR) of 22.6 mg/kg/min. Hyperinsulinism was confirmed in the presence of detectable insulin, low ketones, and fatty acid when hypoglycemic. A left grade 4 intraventricular hemorrhage (IVH) was noted in the cranial ultrasound scan during the workup for sepsis on the day of admission. However, magnetic resonance imaging of the brain on day 7 of life revealed extensive bilateral IVH. On day 9, he was initiated on diazoxide, and HH resolved within 48 to 72 hours, allowing increment of feeds while weaning GIR. Ventricular drain for post-hemorrhagic ventriculomegaly was advised but not performed. At 3 months, post-hemorrhagic ventriculomegaly was stable, and there were early signs of neurodevelopmental delay. After discontinuing diazoxide at 4 months of age, he passed an 8-hour fasting study confirming the resolution of HH. Severe hypoglycemia has been associated with cerebral hyperperfusion in preterm infants and potentially could cause IVH. Close monitoring and prompt intervention in preterm infants to prevent severe hypoglycemia are paramount. In addition to long-term neurodevelopmental follow-up, infants with recurrent hypoglycemia may benefit from neuroimaging and thereby early intervention if required.

MRI of Wallerian Degeneration in the Brainstem: A Pictorial Essay.

Wallerian degeneration of the cerebral peduncle is a common MRI finding after cerebral injury. The degree of peduncular atrophy reflects the extent of damage in the corticospinal tract. The acute phase of Wallerian degeneration is visible with Diffusion-Weighted-Imaging. New investigation with Diffusion-Tensor-Imaging quantifies Wallerian degeneration in the subacute ischemic phase and is a good predictor for later functional recovery after stroke.

Neuroinflammation Mediates Faster Brachial Plexus Regeneration in Subjects with Cerebral Injury.

Our previous investigation suggested that faster seventh cervical nerve (C7) regeneration occurs in patients with cerebral injury undergoing contralateral C7 transfer. This finding needed further verification, and the mechanism remained largely unknown. Here, Tinel's test revealed faster C7 regeneration in patients with cerebral injury, which was further confirmed in mice by electrophysiological recordings and histological analysis. Furthermore, we identified an altered systemic inflammatory response that led to the transformation of macrophage polarization as a mechanism underlying the increased nerve regeneration in patients with cerebral injury. In mice, we showed that, as a contributing factor, serum amyloid protein A1 (SAA1) promoted C7 regeneration and interfered with macrophage polarization in vivo. Our results indicate that altered inflammation promotes the regenerative capacity of the C7 nerve by altering macrophage behavior. SAA1 may be a therapeutic target to improve the recovery of injured peripheral nerves.