The predictive value of left ventricular global longitudinal strain in normotensive critically ill septic patients.

OBJECTIVE: Evaluation of left ventricular systolic function using speckle tracking echocardiography is more sensitive than conventional echocardiographic measurement in detecting subtle left ventricular dysfunction in septic patients. Our purpose was to investigate the predictive significance of left ventricular global longitudinal strain in normotensive septic intensive care patients. METHODS: This observational, prospective cohort study included septic normotensive adults admitted to the intensive care unit between June 1, 2021, and August 31, 2021. Left ventricular systolic function was measured using speckle-tracking echocardiography within 24 hours of admission. RESULTS: One hundred fifty-two patients were enrolled. The intensive care unit mortality rate was 27%. Left ventricular global longitudinal strain was less negative, which indicated worse left ventricular function in non-survivors than survivors (median [interquartile range], -15.2 [-17.2 - -12.5] versus -17.3 [-18.8 - -15.5]; p < 0.001). The optimal cutoff value for left ventricular global longitudinal strain was -17% in predicting intensive care unit mortality (area under the curve, 0.728). Patients with left ventricular global longitudinal strain > -17% (less negative than -17%, which indicated worse left ventricular function) showed a significantly higher mortality rate (39.2% versus 13.7%; p < 0.001). According to multivariate analysis, left ventricular global longitudinal strain was an independent predictor of intensive care unit mortality [OR (95%CI), 1.326 (1.038 - 1.693); p = 0.024], along with invasive mechanical ventilation and Glasgow coma scale, APACHE II, and SOFA risk scores. CONCLUSION: Impaired left ventricular global longitudinal strain is associated with mortality and provided predictive data in normotensive septic intensive care patients.

Capsaicin attenuates excitotoxic-induced neonatal brain injury and brain mast cell-mediated neuroinflammation in newborn rats.

Excitotoxicity and neuroinflammation are key contributors to perinatal brain injuries. Capsaicin, an active ingredient of chili peppers, is a potent exogenous agonist for transient receptor potential vanilloid 1 receptors. Although the neuroprotective and anti-inflammatory effects of capsaicin are well-documented, its effects on excitotoxic-induced neonatal brain injury and neuroinflammation have not previously been investigated. The aim of this study was to investigate the effects of capsaicin on brain damage, brain mast cells, and inflammatory mediators in a model of ibotenate-induced excitotoxic brain injury in neonatal rats. P5 rat-pups were intraperitoneally injected with vehicle, 0.2-, 1-, and 5-mg/kg doses of capsaicin, or the NMDA (N-methyl-d-aspartate) receptor antagonist MK-801 (dizocilpine), 30 min before intracerebral injection of 10 µg ibotenate. The naive-control group received no substance administration. The rat pups were sacrificed one or five days after ibotenate injection. Levels of activin A and interleukin (IL)-1ß, IL-6, and IL-10 in brain tissue were measured using the enzyme-linked immunosorbent assay method. Cortex and white matter thicknesses, white matter lesion size, and mast cells were evaluated in brain sections stained with cresyl-violet or toluidine-blue. Capsaicin improved ibotenate-induced white matter lesions and cerebral white and gray matter thicknesses in a dose-dependent manner. In addition, it suppressed the degranulation and increased number of brain mast cells induced by ibotenate. Capsaicin also reduced the excitotoxic-induced production of neuronal survival factor activin A and of the pro-inflammatory cytokines IL-1ß, and IL-6 in brain tissue. However, IL-10 levels were not altered by the treatments. MK-801, as a positive control, reversed all these ibotenate-induced changes, further confirming the success of the model. Our findings provide, for the first time, evidence for the therapeutic effects of capsaicin against excitotoxic-induced neonatal brain injury and brain mast cell-mediated neuroinflammation. Capsaicin may therefore be a promising candidate in the prevention and/or reduction of neonatal brain damage.

The predictive value of left ventricular global longitudinal strain in normotensive critically ill septic patients / Valor preditivo do strain longitudinal global do ventrículo esquerdo em pacientes críticos normotensos com sepse

ABSTRACT Objective: Evaluation of left ventricular systolic function using speckle tracking echocardiography is more sensitive than conventional echocardiographic measurement in detecting subtle left ventricular dysfunction in septic patients. Our purpose was to investigate the predictive significance of left ventricular global longitudinal strain in normotensive septic intensive care patients. Methods: This observational, prospective cohort study included septic normotensive adults admitted to the intensive care unit between June 1, 2021, and August 31, 2021. Left ventricular systolic function was measured using speckle-tracking echocardiography within 24 hours of admission. Results: One hundred fifty-two patients were enrolled. The intensive care unit mortality rate was 27%. Left ventricular global longitudinal strain was less negative, which indicated worse left ventricular function in non-survivors than survivors (median [interquartile range], -15.2 [-17.2 - -12.5] versus -17.3 [-18.8 - -15.5]; p < 0.001). The optimal cutoff value for left ventricular global longitudinal strain was -17% in predicting intensive care unit mortality (area under the curve, 0.728). Patients with left ventricular global longitudinal strain > -17% (less negative than -17%, which indicated worse left ventricular function) showed a significantly higher mortality rate (39.2% versus 13.7%; p < 0.001). According to multivariate analysis, left ventricular global longitudinal strain was an independent predictor of intensive care unit mortality [OR (95%CI), 1.326 (1.038 - 1.693); p = 0.024], along with invasive mechanical ventilation and Glasgow coma scale, APACHE II, and SOFA risk scores. Conclusion: Impaired left ventricular global longitudinal strain is associated with mortality and provided predictive data in normotensive septic intensive care patients.

RESUMO Objetivo: A avaliação da função sistólica do ventrículo esquerdo utilizando ecocardiografia com speckle tracking é mais sensível do que a medição ecocardiográfica convencional na detecção de disfunções sutis do ventrículo esquerdo em pacientes sépticos. Nosso objetivo foi investigar a significância preditora do strain longitudinal global do ventrículo esquerdo em pacientes sépticos normotensos internados em unidades de terapia intensiva. Métodos: Este estudo de coorte observacional e prospectivo incluiu adultos sépticos normotensos internados em uma unidade de terapia intensiva entre 1° de junho de 2021 e 31 de agosto de 2021. A função sistólica do ventrículo esquerdo foi mensurada utilizando a ecocardiografia com speckle tracking nas primeiras 24 horas após a internação. Resultados: Foram recrutados 152 pacientes. A taxa de mortalidade na unidade de terapia intensiva foi de 27%. O strain longitudinal global do ventrículo esquerdo foi menos negativo, o que indicou pior função do ventrículo esquerdo em não sobreviventes do que em sobreviventes (mediana [intervalo interquartil] -15,2 [-17,2 - -12,5] versus -17,3 [-18,8 - -15,5]; p < 0,001). O valor de corte ótimo para o strain longitudinal global do ventrículo esquerdo foi -17% para prever a mortalidade na unidade de terapia intensiva (área sob a curva de 0,728). Pacientes com strain longitudinal global do ventrículo esquerdo > -17% (menos negativo do que -17%, o que indicou pior função do ventrículo esquerdo) apresentaram taxa de mortalidade significativamente maior (39,2% versus 13,7%; p < 0,001). De acordo com a análise multivariada, o strain longitudinal global do ventrículo esquerdo foi um preditor independente de mortalidade na unidade de terapia intensiva [RC (IC95%), 1,326 (1,038 - 1,693); p = 0,024], com ventilação mecânica invasiva e os escores de risco da escala de coma de Glasgow, APACHE II e SOFA. Conclusão: Alterações do strain longitudinal global do ventrículo esquerdo estão associadas a mortalidade e podem fornecer dados preditivos em pacientes sépticos normotensos internados em unidades de terapia intensiva.

Can hyperoxic stress cause susceptibility to acute seizure in the neonatal period?: a rat study.

Objective: Preterm neonates encounter hyperoxia relatively early, and are more exposed to hyperoxic stress due to their insufficient antioxidant defense mechanisms. This study was planned around the hypothesis that this hyperoxic effect may cause a disposition to future acute seizures. Methods: This study was composed of two main groups Hyperoxy and Control (Room air with normal O2 levels) Groups. Group 1 - hyperoxia (Study): The experimental group consisted of premature newborn rats exposed to hyperoxia with their dams from birth to postnatal day 5. Group 2 - room air (Control): The group was not exposed to hyperoxia and housed the same room air and temperature as their dams. Female, Acute Epilepsy Female, Male, Acute Epilepsy Male, and a total of eight subgroups were formed in both the control and hyperoxia groups. When the rats were two months old, intracranial electrodes were attached to obtain electrocorticography (ECoG) recordings. Pre-model recordings were taken, after which an acute pentylenetetrazole (PTZ) model of absence seizure was induced by the intraperitoneal administration of PTZ at 50 mg/kg. ECoG records were examined using the PowerLab system for 180 min. Spike wave number and duration, Spike wave frequency and amplitude data were evaluated.Results: Seven female and three male rats were exposed to hyperoxia, and a control group of five female and three male rats were included in the study. The median interquartile range for spike wave latency in the hyperoxia and control groups were 1112 (644-1545) and 654 (408-1152), frequency 4476 (3120-7421) and 3934 (2264-4704), and amplitude data 0.68 (0.59-0.79) and 0.52 (0.37-0.67), respectively. Although a difference was observed in median values capable of constituting susceptibility to epilepsy, the difference was not statistically significant (p > 0.05). In terms of gender, spike-wave counts were significantly higher in female rats (p < 0.05). Females exposed to hyperoxia were more susceptible to epilepsy than both males and females in the control group (p < 0.05).Conclusion: Exposure to hyperoxia in the first days of life of premature neonates due to their susceptibility to oxidative stress and insufficient antioxidant mechanisms, can cause a disposition to acute seizures. As a result, females exposed to hyperoxia during the neonatal period may be prone to epilepsy in maturity.

Activation of TRESK background potassium channels by cloxyquin exerts protective effects against excitotoxic-induced brain injury and neuroinflammation in neonatal rats.

We investigated effects of activation of TRESK channels by selective activator cloxyquin on excitotoxic-induced brain injury and neuroinflammation involving brain mast cells and inflammatory cytokines in neonatal rats. Three different doses of cloxyquin (0.2, 1 and 5 mg/kg) were studied in ibotenate-induced perinatal brain injury (PBI) in P5 rat-pups. Cerebral lesions and mast cells in coronal brain sections were evaluated. Concentrations of activin A, IL-1ß, IL-6 and IL-10 in brain homogenates were measured using ELISA. Cloxyquin dose-dependently exerted protective effects against excitotoxic-induced neonatal brain injury and neuroinflammation. TRESK channels may be a promising new target for the treatment of PBIs.

Epidemiologic and clinical characteristics of neonates with late-onset COVID-19: 1-year data of Turkish Neonatal Society.

The literature on neonates with SARS-CoV-2 is mainly concerned with perinatal cases, and scanty data are available about environmentally infected neonates. To fill knowledge gaps on the course and prognosis of neonatal cases, we analyzed 1-year data from the Turkish Neonatal Society in this prospective cohort study of neonates with postnatal transmission. Data from 44 neonatal intensive care units (NICUs), of neonates with positive RT-PCR results at days 5-28 of life, were extracted from the online registry system and analyzed. Of 176 cases, most were term infants with normal birth weight. Fever was the most common symptom (64.2%), followed by feeding intolerance (25.6%), and cough (21.6%). The median length of hospitalization was 9 days, with approximately one quarter of infants receiving some type of ventilatory support. Myocarditis (5.7%) was the most common complication during follow-up. Among the clinical findings, cough (odds ratio [OR]: 9.52, 95% confidence interval [CI]: 4.17-21.71), tachypnea (OR: 26.5, 95% CI: 9.59-73.19), and chest retractions (OR: 27.5, 95% CI: 5.96-126.96) were associated with more severe clinical disease. Also, there were significant differences in the C-reactive protein level, prothrombin time (PT), partial thromboplastin time, international normalized ratio, and days in the NICU (p = 0.002, p = 0.012, p = 0.034, p = 0.008, and p < 0.001, respectively) between patients with mild-moderate and severe-critical presentations. A PT above 14 s was a significant predictor of severe/critical cases, with a sensitivity of 64% and specificity of 73%. CONCLUSIONS: Our data showed that late-onset COVID-19 infection in neonates who need hospitalization can be severe, showing associations with high rates of ventilatory support and myocarditis. Cough, tachypnea, and retractions on admission suggest a severe disease course. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04401540. WHAT IS KNOWN: • Neonatal cases of COVID-19 infection are mainly reported as perinatal COVID-19 cases. • Neonates with perinatal transmission have a mild course and favorable prognosis. WHAT IS NEW: • Among symptomatic neonates with late-onset COVID-19 infection, fever was the most common symptom, and almost one quarter of hospitalized cases needed some type of respiratory support. Myocarditis was the most common complication. • The presence of cough, tachypnea, retractions, and a PT above 14 s were associated with an increased risk of severe COVID-19.

The role of clinical signs in the diagnosis of papilledema: development of an algorithm.

PURPOSE: The aim of this study was not only to emphasize the role of clinical signs as well as ophthalmologic evaluation for accurate and differential diagnosis of papilledema (PE), but also to present an instructive algorithm that would help to eliminate unnecessary examinations and treatments. METHOD: The files of 43 patients (ages 0-18) diagnosed with PE were retrospectively reviewed. The study included 25 patients from our pediatric neurology outpatient clinic, who were thought to have PE, and 18 patients, who were referred from the external centers to our hospital with a pre-diagnosis of PE. RESULTS: Of the 43 patients, 28 had PE, 8 had pseudopapilledema (PPE), and 7 had optic nerve pathologies (ONP). For patients who applied directly to our pediatric neurology unit, a margin of error of 8% was detected based on only a simple ophthalmologic examination and an evaluation of clinical findings. For the patients who were forwarded to our pediatric neurology unit from the external centers without examining any clinical findings and with no details, the margin of error was 72%. CONCLUSION: For patients with suspected PE, advanced ophthalmologic opinion is a necessary requirement before invasive radiological examinations are used. When the ophthalmologic evaluation is properly elaborated, the distinction can be made more clearly by using noninvasive methods. In order to determine the gold standard in terms of the methods used in the evaluation of patients who are not clinically diagnosed, new prospective studies with more patients should be planned.

Plasma levels of vasoactive neuropeptides in pediatric patients with migraine during attack and attack-free periods.

BACKGROUND: Increasing evidence suggests that vasoactive neuropeptides such as pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38), substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide are involved in the pathophysiology of migraine in adults, but their role in pediatric migraineurs remains unclear. We prospectively investigated plasma levels of these vasoactive neuropeptides in pediatric migraine patients without aura and compared the results with those of age-matched healthy controls. METHODS: Thirty-eight children aged 6-18 years with migraine without aura and 20 age-matched control subjects were included in the study. Neuropeptides in plasma samples from the controls, and in either the ictal or interictal periods in pediatric migraine without aura, were measured using ELISA. RESULTS: PACAP-38 and vasoactive intestinal peptide levels in both ictal and interictal plasma were higher in the patients with pediatric migraine without aura than in the controls (p < 0.001), although calcitonin gene-related peptide and substance P levels remained unchanged. Otherwise, no significant difference was determined between ictal and interictal periods in terms of all neuropeptide levels. CONCLUSIONS: This study demonstrates increased plasma PACAP-38 and vasoactive intestinal peptide levels, but not calcitonin gene-related peptide and substance P levels, in pediatric patients with migraine during both attack and attack-free periods. The study findings suggest that PACAP-38 and vasoactive intestinal peptide may be implicated in the pathophysiology of migraine, particularly in pediatric migraineurs.

Epilepsy and drug-resistant epilepsy in children with cerebral palsy: A retrospective observational study.

PURPOSE: The objective of this study was to determine risk factors for epilepsy and drug-resistant epilepsy (DRE) development in children with cerebral palsy. METHOD: Two hundred twenty-nine patients presenting to the pediatric neurology clinic and diagnosed as having cerebral palsy between November 2016 and November 2019 were included in the study. Medical histories and clinical, laboratory, and radiological findings were examined retrospectively from patient records in the hospital data system. RESULTS: Girls represented 103 patients (45%) and boys 126 (55%). The patients' mean age was 8.39 ±â€¯4.54 years. Epileptic seizures were present in 120 (52.4%) patients and drug-resistant seizures in 64 (27.9%). The risk of epilepsy was significantly higher in patients with motor or speech impairment, with hearing impairment, or undergoing first seizure in the neonatal period. We also observed a higher risk of epilepsy in patients with psychiatric comorbidity, particularly autism spectrum disorder. The risk of epilepsy was also higher in patients with microcephaly or quadriplegic cerebral palsy and in patients with focal and generalized epileptiform abnormality on electroencephalograms (EEGs). However, no significant difference was identified when all these factors were evaluated in terms of the risk of developing DRE. CONCLUSION: Patients with cerebral palsy have high comorbid epilepsy rates. We think that the risk of epilepsy may be higher in patients undergoing first seizure in the neonatal period, with microcephaly, with quadriplegic type cerebral palsy, and with additional psychiatric comorbidity. The rate of DRE development was very low in patients with normal EEG findings or with only background rhythm abnormalities on first EEGs during neonatal seizures. This may be regarded as a good prognostic factor for nondevelopment of DRE.

The role of obesity and vitamin D deficiency in primary headaches in childhood.

This study evaluates the role of obesity, overweight and vitamin D deficiency in primary headaches in childhood. This retrospective observational study included pediatric patients aged 5-17 years admitted to the pediatric neurology clinic with headaches between January 2015 and August 2018 and diagnosed with primary headache based on ICHD III-beta criteria. The control group consisted of healthy children without headache admitted to the pediatric outpatient clinic for check-ups before engaging in athletic or school activities. The control and patient groups were at the same risk of low 25(OH)D3 levels. The study population was divided into three groups-patients with migraine (group A), patients with tension-type headache (TTH) (group B) and the control group (group C). Participants' demographic data, medical histories, physical examination findings and laboratory results were retrieved retrospectively from the patient charts. BMI was significantly higher in patients with primary headache, the risk of primary headache increasing in patients with a BMI in excess of 25. Comparison of the patients with primary headache and the control group revealed lower 25(OH)D levels in the primary headache group, although the difference was not statistically significant. Girls with primary headache had significantly lower 25(OH)D levels than boys. A relationship may be present between overweight, obesity and primary headache, while female gender may be suggested as a negative factor for primary headache. Patients should be advised to lose weight if BMI indicates overweight or obesity.

Nasal intermittent positive pressure ventilation with or without very early surfactant therapy for the primary treatment of respiratory distress syndrome.

AIM: Current evidence suggests that nasal intermittent positive pressure ventilation (NIPPV) as a primary treatment for RDS reduces the duration of invasive mechanical ventilation (MV) comparing with nasal continuous airway pressure (NCPAP). We aimed to evaluate whether very early surfactant treatment decreases the need for MV when used in premature infants treated with early NIPPV soon after birth. METHODS: The inclusion criteria of this prospective cohort study were a gestational age of 24-31(6/7) weeks and supplemental oxygen with the evidence of labored breathing within 60 min. Infants were stabilized on NCPAP and then continued with NIPPV, following early surfactant treatment, or were only put on NIPPV. Thirty infants in the NIPPV group and 29 infants in the NIPPV + SURFACTANT group met the inclusion criteria. Primary end-point was the need of MV in the first 72 h of life according to the predefined criteria. RESULTS: The failure rate was significantly lower in the NIPPV + SURFACTANT group compared with the NIPPV group (37.9% and 66.7% respectively, p < 0.05). All other results, including bronchopulmonary dysplasia and death, were similar between the groups. CONCLUSION: NIPPV failure was significantly lower when combined with surfactant treatment, which indicates the critical role of early surfactant treatment in reducing the need for invasive ventilation.

Effect of induced hypothermia on lipopolysaccharide-induced lung injury in neonatal rats.

OBJECTIVES: Recent data suggest that induced hypothermia has some protective effects on experimental lung injury. We aimed to evaluate the protective effect of mild hypothermia in a rat model of lipopolysaccharide (LPS) induced neonatal lung injury. METHODS: Wistar rat pups were divided into four groups, specifically: (i) A control group, with no LPS administration and maintained in room air; (ii) A LPS group, with antenatal LPS administrated and maintained in room air; (iii) A LPS + hypothermia group, with antenatal LPS administrated and exposed to hypothermia; (iv) A hypothermia group, with no LPS administration and exposed to hypothermia. Intraperitoneal LPS was injected into maternal rats at the 19th and 20th gestational days to establish a neonatal lung injury model. Mild hypothermia was started at the postnatal 24th hour and continued during 24 h. At the postnatal 7th day, the rats were sacrificed and lung samples were evaluated for immunohistochemical tests and proinflammatory gene expression levels. RESULTS: Hypothermia therapy attenuated the damaging effects of antenatal LPS administration. Furthermore, hypothermia therapy reduced gene expression of pro-inflammatory cytokines (IL-6, IL-1α, IL-1ß, TNF-α) and induced the expression of a potent anti-inflammatory cytokine (IL-10). CONCLUSION: The results of this study indicated that mild hypothermia therapy is effective in an LPS induced neonatal lung injury model. If these results are supported by further studies, hypothermia may also be a new therapy option for preventing bronchopulmonary dysplasia.

Nasopharyngeal mature teratoma in the newborn.

Teratomas which originate from two or three germ layers are the most common congenital tumors of the childhood and are usually observed in the sacrococcygeal region. The nasopharynx is a considerably rare localization. Nazopharyngeal tumors may lead to significant findings including apnea, respiratory distress and stridor in newborns. In this study, a female newborn who developed respiratory distress minutes after cesarean delivery was presented. Examination following a difficult intubation and radiological examination revealed presence of a nasopharyngeal mass in the baby who was born at the 30(th) gestational age from a 30-year old primipar woman. The nasopharyngeal mass was excised and histopathological examination revealed mature teratoma. Although nasopharyngeal teratoma is a benign tumor, it may lead to urgency of airway management in the newborn. In this case presentation, the differential diagnosis and treatment of nasopharyngeal teratoma was discussed in accompaniment with the literature information.

Protective effects of pentoxifylline on lipopolysaccharide-induced white matter injury in a rat model of periventricular leukomalasia.

OBJECTIVE: To investigate the potential neuroprotective effect of maternal pentoxifylline (PNTX) treatment in endotoxin-induced periventricular leukomalasia (PVL) in the developing rat brain. METHOD: Intraperitoneal injection of lipopolysaccharide was administered on two of three Wistar pregnant rats to establish PVL. To obtain PNTX-treated group, one of the two dams were injected with PNTX. The control group was treated with saline. Rat pups were grouped as control, maternal LPS-treated group and PNTX + LPS-treated group. At 7th postnatal days, apoptosis and hypomyelination were evaluated. Apoptosis was evaluated by caspase-3 and terminal deoxynucleotidyl transferase [TdT] dUTP nick endlabelling reaction (TUNEL) immunostaining. To assess hypomyelination, myelin basic protein (MBP) staining, as a marker of myelination, was evaluated. RESULTS: MBP staining was significantly less and weaker in the brains of the LPS-treated group as compared with the PNTX-treated group. PNTX treatment significantly reduced the number of apoptotic cells in the periventricular WM shown on Tunel and caspase-3. CONCLUSIONS: Presented study is first indicated that PNTX may provide protection against an LPS-induced inflammatory response and WMI in the developing rat brain. Our results also suggest that PNTX treatment in pregnant women with maternal or placental infection may minimize the risk of PVL and cerebral palsy.

Neuroprotective effect of neotrofin in a neonatal rat model of periventricular leukomalacia.

Periventricular leukomalacia (PVL) is the dominant form of brain injury in premature infants and no specific treatment is currently available. Neotrofin, a neurotrophin agonist, has been shown to provide neuroprotection in several in vivo and in vitro studies. The aim of this study was to investigate the neuroprotective effect of neotrofin treatment after endotoxin induced PVL in a rat model. Wistar rat pups were divided into four groups as: (1) control, (2) lipopolysaccharide (LPS)-administered group, (3) LPS-administered and prenatal maternal neotrofin-treated group and (4) LPS-administered and postnatal neotrofin-treated group. Intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) was administered consecutively at the 18th and 19th embryonic days to establish endotoxin-induced PVL model. In the prenatal treatment group dams received an i.p. injection of neotrofin (60 mg/kg) following after the second LPS dose; and in the postnatal treatment group rat pups received i.p. injection of neotrofin (60 mg/kg) at birth. At P7, apoptosis and hypomyelination in periventricular white matter were evaluated by immunohistochemical assessments. The prenatal maternal neotrofin treatment significantly reduced the number of apoptotic cell death and greatly prevented LPS-stimulated loss of hypomyelinization. However, neotrofin treatment in the postnatal period was not as effective as intrauterine treatment. Given our results, neotrofin may be useful in reducing brain injury and possessing clinical relevance for the treatment of white matter injury in newborns.

Maternal prenatal omega-3 fatty acid supplementation attenuates hyperoxia-induced apoptosis in the developing rat brain.

Supraphysiologic amounts of oxygen negatively influences brain maturation and development. The aim of the present study was to evaluate whether maternal ω-3 long-chain polyunsaturated fatty acid (ω-3 FA) supplementation during pregnancy protects the developing brain against hyperoxic injury. Thirty-six rat pups from six different dams were divided into six groups according to the diet modifications and hyperoxia exposure. The groups were: a control group (standard diet+room air), a hyperoxia group (standard diet+80% O2 exposure), a hyperoxia+high-dose ω-3 FA-supplemented group, a hyperoxia+low-dose ω-3 FA-supplemented group, a room air+low-dose ω-3 FA-supplemented+group, and a room air+high dose ω-3 FA-supplemented group. The ω-3 FA's were supplemented as a mixture of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) from the second day of pregnancy until birth. Rat pups in the hyperoxic groups were exposed to 80% oxygen from birth until postnatal day 5 (P5). At P5, all animals were sacrificed. Neuronal cell death and apoptosis were evaluated by cell count, TUNEL, and active Caspase-3 immunohistochemistry. Histopathological examination showed that maternally ω-3 FA deficient diet and postnatal hyperoxia exposure were associated with significantly lower neuronal counts and significantly higher apoptotic cell death in the selected brain regions. Ω-3 FA treatment significantly diminished apoptosis, in the selected brain regions, in a dose dependent manner. Our results suggest that the maternal ω-3 FA supply may protect the developing brain against hyperoxic injury.

Maternal omega-3 fatty acid supplementation protects against lipopolysaccharide-induced white matter injury in the neonatal rat brain.

OBJECTIVES: Periventricular leukomalacia (PVL) is the predominant form of brain injury in premature infants, and no specific treatment currently exists for this condition. We have evaluated whether maternal omega-3 fatty acid (ω3 FA) treatment reduces endotoxin-induced PVL in the developing rat brain. METHODS: Wistar rats with dated pregnancies were fed a standard diet or a diet enriched in ω3 FA (70% docosahexaenoic acid + 30% eicosapentaenoic acid mixture) during gestation. Intraperitoneal injection of lipopolysaccharide (LPS) was administered consecutively on the 18th and 19th embryonic days to establish the endotoxin-induced PVL rat model. The animals were divided into four groups: (i) control, (ii) PVL, (iii) PVL+low-dose ω3 FA and (iv) PVL+high-dose ω3 FA. At day P7, apoptosis and hypomyelination in periventricular white matter were evaluated by immunohistochemical assessments. RESULTS: High-dose maternal ω3 FA treatment reduced brain weight loss. Maternal ω3 FA treatment given either in low or high doses greatly decreased caspase-3 immunoreactivity and increased myelin basic protein immunoreactivity, indicating a decrease in apoptosis and hypomyelination. CONCLUSION: Considering that no specific treatment is available for PVL, maternal ω3 FA supplementation may provide a nutritional strategy to limit periventricular white matter damage caused by infections during pregnancy.