Hypoxic-ischemic Injury Research Articles

Early Postoperative Neurologic Events Are Associated With Worse Outcome and Fatal Midterm Survival After Adult Heart Transplantation.

Background Neurologic events during primary stay in heart transplant (HTx) recipients may be associated with reduced outcome and survival, which we aim to explore with the current study. Methods and Results We screened and included all patients undergoing HTx in our center between September 2010 and December 2022 (n=268) and checked for the occurrence of neurologic events within their index stay. Neurologic events were defined as ischemic stroke, hemorrhage, hypoxic ischemic injury, or acute symptomatic neurologic dysfunction without central nervous system injury. The cohort was then divided into recipients with (n=33) and without (n=235) neurologic events after HTx. Using a multivariable Cox regression model, the association of neurologic events after HTx and survival was assessed. Recipients with neurologic events displayed a longer intensive care unit stay (30 versus 16 days; P=0.009), longer mechanical ventilation (192 versus 48 hours; P<0.001), and higher need for blood transfusion, and need for hemodialysis after HTx was substantially higher (81% versus 55%; P=0.01). Resternotomy (36% versus 26%; P=0.05) and mechanical life support (extracorporeal life support) after HTx (46% versus 24%; P=0.02) were also significantly higher in patients with neurologic events. Covariable-adjusted multivariable Cox regression analysis revealed a significant independent association of neurologic events and increased 30-day (hazard ratio [HR], 2.5 [95% CI, 1.0-6.0]; P=0.049), 1-year (HR, 2.2 [95% CI, 1.1-4.3]; P=0.019), and overall (HR, 2.5 [95% CI, 1.5-4.2]; P<0.001) mortality after HTx and reduced Kaplan-Meier survival up to 5 years after HTx (P<0.001). Conclusions Neurologic events after HTx were strongly and independently associated with worse postoperative outcome and reduced survival up to 5 years after HTx.

Acute Kidney Injury and Abnormalities on Brain Magnetic Resonance Imaging or Death in Infants with Hypoxic-Ischemic Encephalopathy: A Case-Control Study.

This study aimed to analyze the association between acute kidney injury (AKI) and abnormalities on brain magnetic resonance imaging (MRI) or death in neonates treated with therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE). This is a retrospective case-control analysis of 380 neonates born at ≥35 weeks' gestation treated with therapeutic hypothermia for HIE. Death or abnormal brain MRI using the basal ganglia watershed scoring system was compared between neonates with and without AKI. A total of 51 (13.4%) neonates had AKI. Infants with AKI had higher rates of the composite of death or abnormal brain MRI (74.5 vs. 38.3%; p < 0.001). Rate of death (21.6 vs. 5.5%; p < 0.001) and severe abnormalities on MRI or death (43.1 vs. 19.1%; p < 0.001) were also higher in neonates with AKI. AKI is strongly associated with abnormalities on brain MRI or death in neonates with HIE. Identification of AKI in this patient population may be helpful in guiding clinical management and predicting potential neurodevelopmental impairment. · Neonates with HIE are at increased risk for AKI.. · AKI is associated with hypoxic-ischemic injury on brain MRI or death among neonates with HIE.. · Identification of AKI in infants with HIE may help predict neurodevelopmental impairment..

Oxidative Stress Markers in Human Brain and Placenta May Reveal the Timing of Hypoxic-Ischemic Injury: Evidence from an Immunohistochemical Study.

During pregnancy, reactive oxygen species (ROS) serve as crucial signaling molecules for fetoplacental circulatory physiology. Oxidative stress is thought to sustain the pathogenesis and progression of hypoxic-ischemic encephalopathy (HIE). A retrospective study was performed on the brains and placentas of fetuses and newborns between 36-42 weeks of gestation (Group_1: Fetal intrauterine deaths, Group_2: Intrapartum deaths, Group_3: Post-partum deaths, Control group sudden neonatal death); all groups were further divided into two subgroups (Subgroup_B [brain] and Subgroup_P [placenta]), and the study was conducted through the immunohistochemical investigations of markers of oxidative stress (NOX2, 8-OHdG, NT, iNOS), IL-6, and only on the brain samples, AQP4. The results for the brain samples suggest that NOX2, 8-OHdG, NT, iNOS, and IL-6 were statistically significantly expressed above the controls. iNOS was more expressed in the fetal intrauterine death (Group_1) and less expressed in post-partum death (Group_3), while in intrapartum death (Group_2), the immunoreactivity was very low. IL-6 showed the highest expression in the brain cortex of the fetal intrauterine death (Group_1), while intrapartum death (Group_2) and post-partum death (Group_3) showed weak immunoreactivity. Post-partum death (Group_3) placentas showed the highest immunoreactivity to NOX2, which was almost double that of the fetal intrauterine death (Group_1) and intrapartum death (Group_2) placentas. Placental tissues of fetal intrauterine death (Group_1) and intrapartum death (Group_2) showed higher expression of iNOS than post-partum death (Group_3), while the IL-6 expression was higher in the fetal intrauterine death (Group_1) than the post-partum death (Group_3). The AQP4 was discarded as a possible marker because the immunohistochemical reaction in the three groups of cases and the control group was negative. The goal of this study, from the point of view of forensic pathology, is to provide scientific evidence in cases of medical liability in the Obstetric field to support the clinical data of the timing of HIE.

The Use of Contrast-Enhanced Ultrasound (CEUS) in the Evaluation of the Neonatal Brain.

In recent years, advancements in technology have allowed the use of contrast-enhanced ultrasounds (CEUS) with high-frequency transducers, which in turn, led to new possibilities in diagnosing a variety of diseases and conditions in the field of radiology, including neonatal brain imaging. CEUSs overcome some of the limitations of conventional ultrasounds (US) and Doppler USs. It allows the visualization of dynamic perfusion even in the smallest vessels in the whole brain and allows the quantitative analysis of perfusion parameters. An increasing number of articles are published on the topic of the use of CEUSs on children each year. In the area of brain imaging, the CEUS has already proven to be useful in cases with clinical indications, such as hypoxic-ischemic injuries, stroke, intracranial hemorrhages, vascular anomalies, brain tumors, and infections. We present and discuss the basic principles of the CEUS and its safety considerations, the examination protocol for imaging the neonatal brain, and current and emerging clinical applications.

Temporal Evolution of Signal Alterations in the Deep Gray Nuclei in term Neonates With Hypoxic-Ischemic Brain Injury: A Comprehensive Review.

The deep gray nuclei are paired interconnected gray nuclei comprising the basal ganglia and thalami. Injury to the deep gray nuclei secondary to hypoxic-ischemic injury is associated with poor short- and long-term clinical outcomes. The signal changes following hypoxic-ischemic injury are dynamic and evolve over a period of time from injury to resolution. Radiologically relevant events following hypoxic-ischemic injury include the onset of anaerobic metabolism immediately following hypoxic-ischemic injury, increase in cytotoxic edema followed by its resolution, and the onset and progression of neuronal necrosis and gliosis. Appearance of lactate peak on proton spectroscopy is the initial radiologic evidence of hypoxic-ischemic injury. Diffusion-weighted imaging has the highest prognostic value and pseudo-normalizes following 1 week of hypoxic-ischemic injury. Recommended timing for magnetic resonance imaging (MRI) is between 4 and 7 days. MR imaging performed between 1 and 6 months underestimates the extent of injury because radiologic changes are subtle. This review provides a detailed timeline of radiologic abnormalities in the deep gray nuclei following hypoxic-ischemic injury.

Unequal Cerebral Magnetic Resonance Imaging Changes in Perinatal Hypoxic Ischemic Injury of Term Neonates.

Perinatal hypoxic ischemic injury (HII) has a higher prevalence in the developing world. One of the primary concepts for suggesting that an imaging pattern reflects a global insult to the brain is when the injury is noted to be bilateral and symmetric in distribution. In the context of HII in term neonates, this is either bilateral symmetric ( a ) peripheral/watershed (WS) injury or ( b ) bilateral symmetric basal-ganglia-thalamus (BGT) pattern, often with the peri-Rolandic and hippocampal injury. Unilateral, asymmetric, or unequal distribution of injury may therefore be misdiagnosed as perinatal arterial ischemic stroke. We aimed to determine the prevalence of unequal cerebral injury in HII, identify patterns, and determine their relationship with existing classification of HII. Review of brain magnetic resonance imaging from a database of children with HII. Reports with any unequal pattern of injury were included and further classified as a unilateral, bilateral asymmetric, or symmetric but unequal degree pattern of HII. A total of 1213 MRI scans in patients with a diagnosis of HII revealed 156 (13%) with unequal involvement of the hemispheres: unilateral in 2 of 1213 (0.2%) (involvement only in the WS), asymmetric in 48 of 1213 (4%) (WS in 6 [0.5%], BGT in 4 [0.3%], and combined BGT and WS in 38 [3.1%]), and bilateral symmetric but unequal degree in 106 of 1213 (8.7%) (WS in 20 [1.6%], BGT in 17 [1.4%], and combined BGT and WS in 69 [5.7%]). The majority of children with cerebral palsy due to HII demonstrate a characteristic bilateral symmetric pattern of injury. In our study, 13% demonstrated an unequal pattern. Differentiation from perinatal arterial ischemic stroke, which is mostly unilateral and distributed typically in the middle cerebral artery territory, should be possible and recognition of the typical BGT or WS magnetic resonance imaging patterns should add confidence to the diagnosis, in such scenarios.

A narrative review of neuromonitoring modalities in critically ill children.

Acute neurologic injury is common in critically ill children. Some conditions - such as traumatic brain injury, meningitis, and hypoxic-ischemic injury following cardiac arrest - require careful consideration of cerebral physiology. Specialized neuromonitoring techniques provide insight regarding patient-specific and disease-specific insight that can improve diagnostic accuracy, aid in targeting therapeutic interventions, and provide prognostic information. In this review, we will discuss recent innovations in invasive (e.g., intracranial pressure monitoring and related computed indices) and noninvasive (e.g., transcranial doppler, near-infrared spectroscopy) neuromonitoring techniques used in traumatic brain injury, central nervous system infections, and after cardiac arrest. We will discuss the pertinent physiological mechanisms interrogated by each technique and discuss available evidence for potential clinical application. We will also discuss the use of innovative neuromonitoring techniques to detect and manage neurologic complications in critically ill children with systemic illness, focusing on sepsis and cardiorespiratory failure requiring extracorporeal membrane oxygenation.

Neuroprotective Effects of Delayed TGF-β1 Receptor Antagonist Administration on Perinatal Hypoxic-Ischemic Brain Injury

Hypoxic-ischemic (HI) brain injury in neonatal encephalopathy triggers a wave of neuroinflammatory events attributed to causing the progressive degeneration and functional deficits seen weeks after the primary damage. The cellular processes mediating this prolonged neurodegeneration in HI injury are not sufficiently understood. Consequently, current therapies are not fully protective. In a recent study, we found significant improvements in neurologic outcomes when a small molecule antagonist for activin-like kinase 5 (ALK5), a transforming growth factor beta (TGF-β) receptor was used as a therapeutic in a rat model of moderate term HI. Here, we have extended those studies to a mouse preterm pup model of HI. For these studies, postnatal day 7 CD1 mice of both sexes were exposed to 35–40 min of HI. Beginning 3 days later, SB505124, the ALK5 receptor antagonist, was administered systemically through intraperitoneal injections performed every 12 h for 5 days. When evaluated 23 days later, SB505124-treated mice had ∼2.5-fold more hippocampal area and ∼2-fold more thalamic tissue. Approximately 90% of the ipsilateral hemisphere (ILH) was preserved in the SB505124-treated HI mice compared to the vehicle-treated HI mice, where the ILH was ∼60% of its normal size. SB505124 also preserved the subcortical white matter. SB505124 treatment preserved levels of aquaporin-4 and n-cadherin, key proteins associated with blood-brain barrier function. Importantly, SB505124 administration improved sensorimotor function as assessed by a battery of behavioral tests. Altogether, these data lend additional support to the conclusion that SB505124 is a candidate neuroprotective molecule that could be an effective treatment for HI-related encephalopathy in moderately injured preterm infants.

Neuroprotection after cardiac arrest with 2-iminobiotin: a single center phase IIa study on safety, tolerability, and pharmacokinetics.

Brain injury is a serious problem in patients who survive out-of-hospital cardiac arrest (OHCA). Neuroprotective drugs could reduce hypoxic-ischemic reperfusion injury. The aim of this study was to investigate the safety, tolerability, and pharmacokinetics (PK) of 2-iminobiotin (2-IB), a selective inhibitor of neuronal nitric oxide synthase. Single-center, open-label dose-escalation study in adult OHCA patients, investigating three 2-IB dosing schedules (targeting an AUC0-24h of 600-1,200 ng*h/m in cohort A, of 2,100-3,300 ng*h/mL in cohort B, and 7,200-8,400 of ng*h/mL in cohort C). Safety was investigated by monitoring vital signs until 15 min after study drug administration and adverse events up to 30 days after admission. Blood sampling for PK analysis was performed. Brain biomarkers and patient outcomes were collected 30 days after OHCA. A total of 21 patients was included, eight in cohort A and B and five in cohort C. No changes in vital signs were observed, and no adverse events related to 2-IB were reported. A two-compartment PK model described data the best. Exposure in group A (dosed on bodyweight) was three times higher than targeted (median AUC0-24h 2,398 ng*h/mL). Renal function was an important covariate; therefore, in cohort B, dosing was performed on eGFR on admission. In cohort B and C, the targeted exposure was met (median AUC0-24h 2,917 and 7,323 ng*h/mL, respectively). The administration of 2-IB to adults after OHCA is feasible and safe. PK can be well predicted with correction for renal function on admission. Efficacy studies with 2-IB after OHCA are needed.

Does resveratrol improve cognition in humans? A scientometric study to an in-depth review.

In order to understand the different processes and mechanisms of cognitive function and resveratrol (RES) as an active participant in pathophysiological events that affect cognitive function. First, the Web of Science (core collection) was selected as the data source. To ensure the comprehensiveness and accuracy of the search data, the index was selected as "SCI-EXPANDED", and the search formula was TS = resveratrol AND TS = ("cognitive" OR "memory" OR "cognition" OR "mood"). Next, details of authors, keywords, journals, countries, institutions, references, and more were analyzed by CiteSpace and VOSviewer software. Finally, we explored the mechanism by which RES could improve cognitive impairment, that involves healthy young adults, healthy elderly, post-menopausal women, and diseases involving Alzheimer's disease (AD), diabetes-related cognitive impairment, mental illness, post-stroke cognitive impairment, and neonatal hypoxic-ischemic injury. 287 valid papers were obtained. The scientometric results demonstrated 287 papers used in this study came from 1601 authors from 443 organizations in 38 countries, published in 169 journals, and cited 13,680 literatures from 2431 journals. Depression, AD, cerebral ischemia, diabetic cognitive impairment, and cognitive function in the elderly are all keywords of the co-occurrence network. This study supports the hypothesis that chronic RES intake may positively affect brain function. But it has become challenging to determine the optimal dose, time and duration of RES and improve the bioavailability of RES, which many researchers need to overcome.

Оцінка імунологічних показників у дітей з порушеннями поведінки внаслідок перинатальних цереброваскулярних уражень

Purpose - a comprehensive study of the immune system of patients with deviant behavior due to perinatal pathology. Materials and methods. The sample consisted of 43 boys aged 7 to 15 years with a history of perinatal hemorrhagic and hypoxic-ischemic cerebrovascular injuries, which later provoked various forms of non-psychotic deviant behavior. To check the results, a control group consisting of 43 mentally and physically healthy children and adolescents was selected. The main group, which showed persistent deviant behavior, was prescribed a drug whose active substance is dalargin, a peptide compound whose structure includes 6 amino acid residues. Clinical-amnestic, clinical-psychopathological, neurosonography was used to diagnose perinatal cerebrovascular injuries in newborns (in history) with subsequent use of computed tomography (CT) and magnetic resonance imaging (MRI) methods, statistical data processing was carried out using «SPSS 16.0» and «Excel» programs from the «Microsoft Office 2003» package. Results. The study of T- and so-called T-active lymphocytes of the peripheral blood showed that before treatment, a significant decrease in the content of these cells was observed in children (to 4.26±0.80% and 22.42±0.69% against 65.81±1.66% 44.42±1.25% in the control group, p&gt;0.05). Proliferative activity changes significantly in response to T- and B-mitogens. Proliferative activity recovered completely (25.56±3.26% and 59.72±2.19% vs. 57.23±1.51% in the control group). Conclusions. Children and adolescents with pronounced deviant behavior of residual organic genesis, resistant to traditional therapy, are characterized by significant changes in the immune status caused by dysimmunoglobulinemia, imbalance of the lymphocyte subpopulation, suppression of the functional activity of these populations on mitogens, which indicates secondary immunodeficiency. The therapeutic effectiveness of the dalargin-peptide compound is determined by its function as an immunocorrector in treatment-resistant behavioral disorders. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Hypothermia Treatment after Hypoxia-Ischemia in Glutathione Peroxidase-1 Overexpressing Mice

The developing brain is uniquely susceptible to oxidative stress, and endogenous antioxidant mechanisms are not sufficient to prevent injury from a hypoxic-ischemic challenge. Glutathione peroxidase (GPX1) activity reduces hypoxic-ischemic injury. Therapeutic hypothermia (HT) also reduces hypoxic-ischemic injury, in the rodent and the human brain, but the benefit is limited. Here, we combined GPX1 overexpression with HT in a P9 mouse model of hypoxia-ischemia (HI) to test the effectiveness of both treatments together. Histological analysis showed that wild-type (WT) mice with HT were less injured than WT with normothermia. In the GPX1-tg mice, however, despite a lower median score in the HT-treated mice, there was no significant difference between HT and normothermia. GPX1 protein expression was higher in the cortex of all transgenic groups at 30 min and 24 h, as well as in WT 30 min after HI, with and without HT. GPX1 was higher in the hippocampus of all transgenic groups and WT with HI and normothermia, at 24 h, but not at 30 min. Spectrin 150 was higher in all groups with HI, while spectrin 120 was higher in HI groups only at 24 h. There was reduced ERK1/2 activation in both WT and GPX1-tg HI at 30 min. Thus, with a relatively moderate insult, we see a benefit with cooling in the WT but not the GPX1-tg mouse brain. The fact that we see no benefit with increased GPx1 here in the P9 model (unlike in the P7 model) may indicate that oxidative stress in these older mice is elevated to an extent that increased GPx1 is insufficient for reducing injury. The lack of benefit of overexpressing GPX1 in conjunction with HT after HI indicates that pathways triggered by GPX1 overexpression may interfere with the neuroprotective mechanisms provided by HT.

FGF21 modulates hippocampal cold-shock proteins and CA2-subregion proteins in neonatal mice with hypoxia-ischemia.

Fibroblast growth factor 21 (FGF21) is a neuroprotectant with cognitive enhancing effects but with poorly characterized mechanism(s) of action, particularly in females. Prior studies suggest that FGF21 may regulate cold-shock proteins (CSPs) and CA2-marker proteins in the hippocampus but empirical evidence is lacking. We assessed in normothermic postnatal day (PND) 10 female mice, if hypoxic-ischemic (HI) brain injury (25 min 8% O2/92% N2) altered endogenous levels of FGF21 in serum or in the hippocampus, or its receptor β-klotho. We also tested if systemic administration of FGF21 (1.5 mg/kg) modulated hippocampal CSPs or CA2 proteins. Finally, we measured if FGF21 therapy altered markers of acute hippocampal injury. HI increased endogenous serum FGF21 (24 h), hippocampal tissue FGF21 (4d), and decreased hippocampal β-klotho levels (4d). Exogenous FGF21 therapy modulated hippocampal CSP levels, and dynamically altered hippocampal CA2 marker expression (24 h and 4d). Finally, FGF21 ameliorated neuronal damage markers at 24 h but did not affect GFAP (astrogliosis) or Iba1 (microgliosis) levels at 4d. FGF21 therapy modulates CSP and CA2 protein levels in the injured hippocampus. These proteins serve different biological functions, but our findings suggest that FGF21 administration modulates them in a homeostatic manner after HI. Hypoxic-ischemic (HI) injury in female post-natal day (PND) 10 mice decreases hippocampal RNA binding motif 3 (RBM3) levels in the normothermic newborn brain. HI injury in normothermic newborn female mice alters serum and hippocampal fibroblast growth factor 21 (FGF21) levels 24 h post-injury. HI injury in normothermic newborn female mice alters hippocampal levels of N-terminal EF-hand calcium binding protein 2 (NECAB2) in a time-dependent manner. Exogenous FGF21 therapy ameliorates the HI-mediated loss of hippocampal cold-induced RNA-binding protein (CIRBP). Exogenous FGF21 therapy modulates hippocampal levels of CA2-marker proteins after HI.

Diffusion Tensor Imaging to Predict Neurodevelopmental Impairment in Infants after Hypoxic-Ischemic Injury.

Magnetic resonance imaging (MRI) is the standard of care for evaluation of brain injury after hypoxic-ischemic encephalopathy (HIE) in term newborns. This study utilizes diffusion tensor imaging (DTI) to (1) identify infants at highest risk of development of cerebral palsy (CP) following HIE and to (2) identify regions of the brain critical to normal fidgety general movements (GMs) at 3 to 4 months of postterm. Absence of these normal, physiological movements is highly predictive of CP. Term infants treated with hypothermia for HIE from January 2017 to December 2021 were consented for participation and had brain MRI with DTI after rewarming. The Prechtl's General Movements Assessment was performed at 12 to 16 weeks of age. Structural MRIs were reviewed for abnormalities, and DTI data were processed with the FMRIB Software Library. Infants underwent the Bayley Scales of Infant and Toddler Development III test at 24 months. Forty-five infant families were consented; three infants died prior to MRI and were excluded, and a fourth infant was excluded due to diagnosis of a neuromuscular disorder. Twenty-one infants were excluded due to major movement artifact on diffusion images. Ultimately, 17 infants with normal fidgety GMs were compared with 3 infants with absent fidgety GMs with similar maternal and infant characteristics. Infants with absent fidgety GMs had decreased fractional anisotropy of several important white matter tracts, including the posterior limb of the internal capsule, optic radiations, and corpus callosum (p < 0.05). All three infants with absent fidgety GMs and two with normal GMs went on to be diagnosed with CP. This study identifies white matter tracts of the brain critical to development of normal fidgety GMs in infants at 3 to 4 months of postterm using advanced MRI techniques. These findings identify those at highest risk for CP among infants with moderate/severe HIE prior to hospital discharge. · HIE has devastating impacts on families and infants.. · Diffusion MRI identifies infants at highest risk for developing neurodevelopmental impairment.. · Normal general movements of infancy are generated by key white matter tracts..

Diffusion kurtosis imaging and diffusion weighted imaging comparison in diagnosis of early hypoxic–ischemic brain edema

BackgroundHypoxic–ischemic encephalopathy (HIE) refers to cerebral hypoxic–ischemic injury caused by asphyxia during perinatal period, which is one of the important causes of neonatal death and sequelae. Early and accurate diagnosis of HIE is of great significance for the prognostic evaluation of patients. The purpose of this study is to explore the efficacy of diffusion-kurtosis imaging (DKI) and diffusion-weighted imaging (DWI) in the diagnosis of early HIE.MethodsTwenty Yorkshire newborn piglets (3–5 days) were randomly divided into control group and experimental group. DWI and DKI scanning were performed at timepoints of 3, 6, 9, 12, 16, and 24 h after hypoxic–ischemic exposure. At each timepoint, the parameter values obtained by each group scan were measured, and the lesion area of the apparent diffusion coefficient (ADC) map and mean diffusion coefficient (MDC) map were measured. (For better interpretation of this study, we replaced the description of MD with MDC). Then, we completely removed the brain for pathological examination, and observed the state of cells and mitochondria in the ADC/MDC matching area (the actual area of the lesion), and the mismatch area (the area around the lesion).ResultsIn the experimental group, the ADC and MDC values decreased with time, but the MDC decreased more significantly and the change rate was higher. Both MDC and ADC values changed rapidly from 3 to 12 h and slowly from 12 to 24 h. The MDC and ADC images showed obvious lesions at 3 h for the first time. At this time, the area of ADC lesions was larger than that of MDC. As the lesions developed, the area of ADC maps was always larger than that of the MDC maps within 24 h. By observing the microstructure of the tissues by light microscopy, we found that the ADC and MDC matching area in the experimental group showed swelling of neurons, infiltration of inflammatory cells, and local necrotic lesions. Consistent with the observation under light microscope, pathological changes were observed in the matching ADC and MDC regions under electron microscopy as well, including collapse of mitochondrial membrane, fracture of partial mitochondrial ridge, and emergence of autophagosomes. In the mismatching region, the above pathological changes were not observed in the corresponding region of the ADC map.ConclusionsDKI’s characteristic parameter MDC is better than ADC (parameter of DWI) to reflect the real area of the lesion. Therefore, DKI is superior to DWI in diagnosing early HIE.

Effect of type 1 diabetes during pregnancy and lactation on neonatal hypoxia-ischemia injury and apoptotic gene expression.

Hypoxia-ischemia (HI) is one of the major disorders that causes a variety of abnormalities and infant mortality. Type 1 diabetes is one of the most common worldwide metabolic disorders, and its prevalence has become one of the public health concerns of the 21st century. This study aims to evaluate the effect of type 1 diabetes during pregnancy and lactation on vulnerability to neonatal HI in rats. Female Wistar rats (weighing 200 ± 220 g) were randomly assigned into two groups: Group 1 (rats that received 0.5mL/day of normal saline solution) and Group 2 (type 1 diabetes was induced in rats on the second day of pregnancy with a single dose of intraperitoneal injection of alloxan monohydrate [150 mg/kg]). After delivery, offspring were divided into four groups: (a) Control (Co), (b) Diabetic (DI), (c) Hypoxia-ischemia (HI), (d) HI + Diabetic (HI + DI). Seven days after HI induction, neurobehavioral tests were performed, and then cerebral edema, infarct volume, inflammatory factors, Bax-Bcl2 expression, and oxidative stress were measured. The BAX level in the DI + HI (p = 0.0355) group was significantly higher than the HI group. The Bcl-2 expression levels in the HI (p = 0.0027) and DI + HI (p < 0.0001) groups were significantly lower than the DI group. Total antioxidant capacity (TAC) levels in the DI + HI (p < 0.0001) group were significantly lower than HI and CO groups. TNF-α, CRP, and total oxidant status (TOS) levels in the DI + HI (p < 0.0001) group were significantly higher than the HI group. Infarct volume and cerebral edema in the DI + HI (p < 0.0001) group were significantly higher than the HI group. According to the results, type 1 diabetes during pregnancy and lactation increased the destructive effects of HI injury in pups. It also decreased the expression of the anti-apoptotic Bcl-2 and increased the expression BAX apoptosis factor gene in pups.

TO STUDY ON MRI BRAIN FINDINGS IN SEVERE PRE- ECLAMPSIA AND ECLAMPSIA IN PREGNANT WOMEN IN TERTIARY CARE CENTRE-A PROSPECTIVE OBSERVATIONAL STUDY

Background: To corroborate the clinical ndings of severe pre-eclampsia and eclampsia patients with magnetic resonance imaging ndings of brain. This is a 2-year prospective study was conducted in the VMGMC of departme Methods: nt of obstetrics and gynaecology, Solapur. A sample size of 50 patients with severe pre- eclampsia/ eclampsia were included. Each patient was studied comparing under different variables to MRI brain ndings. Comparison was done using appropriate statistical method to ascertain our ndings statistical signicance. MRI revealed Results: abnormal ndings in 52% (26) of the patients, of that most common nding were bilateral PRES (40%), followed by hypoxic ischemic injury (4%), metabolic encephalopathy (2%), infarct (4%) and subacute infarct (2%). Among patients with abnormal MRI ndings 4 of them belong to unregistered group and 22 of them are registered group, most of them are in younger age group of 21 to 25 years. Convulsions, eclampsia, consciousness level, systolic blood pressure, diastolic blood pressure, mean arterial pressure, haemoglobin level (p=0.05, p=0.012, p=0.001, p=0.002, p=0.019, p=0.007, p=0.027) respectively are in line with MRI ndings. Age group, residence, socio economic level, parity status, gestational age, urine albumin level, mode of delivery, MgSO4 (p=0.364, p=1.00, p=0.235, p=0.120, p=0.162, p=0.721, p=0.611, p=0.749) respectively not in line with the MRI ndings. Number of convulsions, type of eclam Conclusions: psia, consciousness level, systolic blood pressure, diastolic blood pressure, mean arterial pressure, haemoglobin level are statistically signicant with MRI ndings so, this ndings in pregnant patients should arise concern and helps in plan of action for better management. Age group, residence, socio economic status, parity, gestational age, urine albumin level, mode of delivery RFT, and MgSo4 were not statistically signicant for MRI ndings

Intracranial Imaging of Preterm Infants with Suspected Hypoxic Ischemic Encephalopathy: Comparing MRI and Ultrasound.

We correlate ultrasound, MRI, and clinical findings in neonates with suspected hypoxic ischemic injury. Recent advances in neuroimaging have led to improved detection of subtle insults associated with neurodevelopmental outcomes, beyond more historically described lesions such as large hemorrhages and hydrocephalus. In this study, we compare cranial ultrasound to MRI for the evaluation of suspected HIE in preterm infants. 147 premature infant patients with paired ultrasound and MRI exams were retrospectively analyzed to compare imaging finding accuracy and clinical value. We confirm that ultrasound is highly sensitive and specific for hydrocephalus, ventricular prominence, and gross structural abnormalities. Ultrasound is not a substitute for MRI in cases of small hemorrhages or white matter injury, however, certain US findings were associated with Apgar score and MRI sequelae of HIE. Choosing between ultrasound and MRI for preterm neonates at risk for intracranial abnormalities based on their strengths can reduce cost and maximize clinical utility. MRI provides a highly sensitive identification of subtle brain injury, yet ultrasound is correlated with the peripartum clinical picture as measured by Apgar score.

Unique Patterns of Ischemic Stroke from Combined Cocaine and Heroin Use: A Case Series (P3-5.031)

<h3>Objective:</h3> To describe cases of multiple territory ischemic stroke in young individuals secondary to combined cocaine and heroin use. <h3>Background:</h3> Abuse of cocaine and heroin has been linked to ischemic stroke via various mechanisms. Cocaine use can lead to vasospasm, direct cerebral vessel damage, or other end-organ damage which can promote clot formation. Heroin use has been linked to hypoxic-ischemic injury, promoting cardioembolism, and rarely hypereosinophilia. The effects of a combination of these two substances on acute ischemic stroke are less frequently reported. <h3>Design/Methods:</h3> Retrospective case series of three individuals. <h3>Results:</h3> <h3>Case 1:</h3> A 37-year-old female with a history of polysubstance use disorder presented after being found down. She was disoriented, confabulating, had ataxia and dysarthria with a NIHSS of 15. MRI revealed symmetric ischemic changes within the bilateral hippocampi, bilateral cerebellar regions, and right occipital lobe. The patient endorsed use of synthetic heroin and cocaine prior to presentation. <h3>Case 2:</h3> A 46-year-old male presented after being found down in a hotel room with an empty syringe, later endorsing combined cocaine and heroin use. On exam, he was severely obtunded and required intubation, NIHSS was 27. MRI revealed symmetric ischemic changes in the bilateral globus pallidus, centrum semiovale, corona radiata, and scattered foci of restricted diffusion in both cerebral hemispheres. <h3>Case 3:</h3> A 46-year-old male with a history of type 2 diabetes mellitus and polysubstance use disorder presented with a 5-day history of altered mental status. Exam notable for apraxia, short term memory loss, and shuffling gait, but NIHSS was 0. Use of cocaine and heroin was identified. MRI revealed bilateral globus pallidus infarcts with petechial hemorrhage, and a right temporal lobe infarct. <h3>Conclusions:</h3> The combined use of cocaine and heroin can lead to multiple territory ischemic stroke plus striking symmetric globus pallidus and/or hippocampus ischemia. <b>Disclosure:</b> Dr. Hasan has nothing to disclose. Dr. Pinna has nothing to disclose. Dr. Lynch has nothing to disclose. Dr. Kim has nothing to disclose.

The Notch pathway regulates autophagy after hypoxic-ischemic injury and affects synaptic plasticity.

Following neonatal hypoxic-ischemia (HI) injury, it is crucial factor to reconstruct neural circuit and maintain neural network homeostasis for neurological recovery. A dynamic balance between the synthesis and degradation of synaptic protein is required for maintaining synaptic plasticity. Protein degradation is facilitated by autophagy. This study aimed to investigate the regulation of synaptic structural plasticity by the Notch pathway, by assessing changes in Notch pathway activation and their effects on synaptic proteins and autophagy after HI injury. The study involved 48 male newborn Yorkshire piglets, each weighing 1.0-1.5kg and 3days old. They were randomly assigned to two groups: the HI group and the Notch pathway inhibitor + HI group (n = 24 per group). Each group was further divided into six subgroups according to HI duration (n = 4 per group): a control subgroup, and 0-6, 6-12, 12-24, 24-48, and 48-72h subgroups. The expression of Notch pathway-related proteins, including Notch1, Hes1, and Notch intracellular domains, increased following HI injury. The expression of autophagy proteins increased at 0-6h and 6-12h post-HI. The expression of synaptic proteins, such as postsynaptic density protein 95 (PSD95) and synaptophysin, increased 6-12h and 12-24h after HI, respectively. Notably, the increased expression of these proteins was reversed by a Notch pathway inhibitor. Transmission electron microscopy revealed the presence of autophagosome structures in synapses. These findings shed light on the underlying mechanisms of neurological recovery after HI injury and may provide insights into potential therapeutic targets for promoting neural circuit reconstruction and maintaining neural network homeostasis.