Effects of cannabidiol in post-stroke mood disorders in neonatal rats.

Background: Neonatal rats can manifest post-stroke mood disorders (PSMD) following middle cerebral artery occlusion (MCAO). We investigated whether cannabidiol (CBD) neuroprotection, previously demonstrated in neonatal rats after MCAO, includes prevention of PSMD development.

Methods: Seven-day-old Wistar rats (P7) underwent MCAO and received either vehicle or 5 mg/kg CBD treatment.

Cannabidiol reduces intraventricular hemorrhage brain damage, preserving myelination and preventing blood brain barrier dysfunction in immature rats.

Intraventricular hemorrhage (IVH) is an important cause of long-term disability in extremely preterm infants, with no current treatment. This study assessed the potential neuroprotective effects of cannabidiol (CBD) in an IVH model using immature rats. IVH was induced in 1-day-old (P1) Wistar rats by left periventricular injection of Clostridial collagenase.

Protein Carbonylation as a Biomarker of Oxidative Stress and a Therapeutic Target in Neonatal Brain Damage.

Oxidative stress (OS) constitutes a pivotal factor within the mechanisms underlying brain damage, for which the immature brain is particularly vulnerable. This vulnerability is caused by the abundance of immature oligodendrocytes in the immature brain, which are highly susceptible to OS-induced harm. Consequently, any injurious process involving OS within the immature brain can lead to long-term myelination impairment.

VCE-005.1, an hypoxia mimetic betulinic acid derivative, induces angiogenesis and shows efficacy in a murine model of traumatic brain injury.

One of the main global causes of mortality and morbidity is traumatic brain injury (TBI). Neuroinflammation and brain-blood barrier (BBB) disruption play a pivotal role in the pathogenesis of acute and chronic TBI onset. The activation of the hypoxia pathway is a promising approach for CNS neurodegenerative diseases, including TBI.

The Role of the Dopamine System in Post-Stroke Mood Disorders in Newborn Rats.

Post-stroke mood disorders (PSMD) affect disease prognosis in adults. Adult rodent models underlie the importance of the dopamine (DA) system in PSMD pathophysiology. There are no studies on PSMD after neonatal stroke.

Neuroprotective Effects of Betulinic Acid Hydroxamate in Intraventricular Hemorrhage-Induced Brain Damage in Immature Rats.

Intraventricular hemorrhage (IVH) is an important cause of long-term disability in extremely preterm infants, with no current treatment. We aimed to study in an IVH model in immature rats the neuroprotective effect of betulinic acid hydroxamate (BAH), a B55α/PP2A activator that inhibits the activity of the hypoxia-inducing factor prolyl-hydroxylase type 2. IVH was induced in 1-day-old (P1) Wistar rats by the left periventricular injection of Clostridial collagenase.

Regulation of Expression of Cannabinoid CB and Serotonin 5HT Receptor Complexes by Cannabinoids in Animal Models of Hypoxia and in Oxygen/Glucose-Deprived Neurons.

Cannabidiol (CBD) is a phytocannabinoid with potential in one of the most prevalent syndromes occurring at birth, the hypoxia of the neonate. CBD targets a variety of proteins, cannabinoid CB and serotonin 5HT receptors included. These two receptors may interact to form heteromers (CB-5HT-Hets) that are also a target of CBD.

Role of 5HT1A Receptors in the Neuroprotective and Behavioral Effects of Cannabidiol in Hypoxic-Ischemic Newborn Piglets.

Hypoxic-ischemic (HI) insults have important deleterious consequences in newborns, including short-term morbidity with neuromotor and cognitive disturbances. Cannabidiol (CBD) has demonstrated robust neuroprotective effects and shows anxiolytic/antidepressant effects as well. These effects are thought to be related to serotonin 5-HT receptor (5HTR) activation.

Cannabidiol Reduces Inflammatory Lung Damage After Meconium Aspiration in Newborn Piglets.

Aim: To assess the effects of cannabidiol (CBD) on lung damage in a piglet model of meconium aspiration syndrome (MAS).

Materials And Methods: Meconium aspiration syndrome was modelled in newborn piglets intratracheal instillation of 20% meconium in saline collected from healthy newborn humans. Piglets were treated i.

Diastolic Dysfunction in Neonates With Hypoxic-Ischemic Encephalopathy During Therapeutic Hypothermia: A Tissue Doppler Study.

Unlabelled: Diastolic dysfunction often complicates myocardial ischemia with increased mortality rates. However, less is known about diastolic function after perinatal asphyxia in neonates with hypoxic-ischemic encephalopathy (HIE) during therapeutic hypothermia (TH) and rewarming.

Aim: The aim of this study was to assess diastolic function with tissue Doppler imaging (TDI) in neonates with moderate-severe HIE during TH and rewarming.

Intraventricular hemorrhage induces inflammatory brain damage with blood-brain barrier dysfunction in immature rats.

Background: We aimed to characterize a preclinical model of intraventricular hemorrhage-induced brain damage (IVH-BD) in extremely low birth weight newborns (ELBWN), to identify potential therapeutic targets based on its pathophysiology.

Methods: IVH was induced in 1-day-old (P1) Wistar rats by left periventricular injection of clostridium collagenase (PVCC). At P6, P14, and P45 IVH-BD (area of damage, motor and cognitive deficits, Lactate/N-acetylaspartate ratio), white matter injury (WMI: ipsilateral hemisphere and corpus callosum atrophy, oligodendroglial population and myelin basic protein signal reduction), blood-brain barrier (BBB) dysfunction (occludin and Mfsd2a expression, Gadolinium leakage) and inflammation (TNFα, TLR4, NFkB, and MMP9 expression; immune cell infiltration), excitotoxicity (Glutamate/N-acetylaspartate), and oxidative stress (protein nitrosylation) were assessed.

Neuroprotective Efficacy of Betulinic Acid Hydroxamate, a B55α/PP2A Activator, in Acute Hypoxia-Ischemia-Induced Brain Damage in Newborn Rats.

There is an increasing evidence of the neuroprotective effects of hypoxia inducing factor prolyl-hydroxylase inhibitors (HIF-PHDi) after hypoxic-ischemic (HI) brain damage (HIBD). We studied the neuroprotective effects of betulinic hydroxamate (BAH), a novel B55α/PP2A activator that dephosphorylates and inhibits PHD2 activity, in a rat model of neonatal HIBD. Seven-day-old (P7) Wistar rats were exposed to hypoxia after left carotid artery electrocoagulation and then received vehicle (HI + VEH) or BAH 3 mg/kg i.

Dexmedetomidine affects cerebral activity in preterm infants.

The use of dexmedetomidine (DEX) has been extended in preterm newborns, but the effects on cerebral activity and their relationship with haemodynamic changes has not been studied.We retrospectively studied the effects of DEX administered to 10 preterm newborns, assessing amplitude-integrated EEG (aEEG) parameters, brain regional SO (brSO), heart rate, non-invasive mean blood pressure (MBP), transcutaneous oxygen saturation (SpO), venous pCO2 and haemoglobin (Hb) values, in two 6-hour periods: one starting 6 hours before the beginning of DEX perfusion and the other 6 hours afterwards.DEX infusion led to brSO decrease not associated to heart rate, MBP, SpO, Hb or pCO2 variation, which suggests that brSO decrease could be related to local vasoconstriction.

Mood disorders in children following neonatal hypoxic-ischemic encephalopathy.

Background: Few studies on the consequences following newborn hypoxic-ischemic encephalopathy (NHIE) assess the risk of mood disorders (MD), although these are prevalent after ischemic brain injury in adults.

Objective: To study the presence of MD in children survivors of NHIE.

Methods: 14 children survivors of NHIE treated with hypothermia and without cerebral palsy and 15 healthy children without perinatal complications were studied aged three to six years for developmental status (Ages and Stages Questionnaire 3 [ASQ-3]) and for socio-emotional status (Preschool Symptom Self-Report [PRESS] and Child Behavior Checklist [CBCL] 1.

Congenital Cutaneous Candidiasis With Systemic Dissemination in a Preterm Infant.

Congenital cutaneous candidiasis is an infrequent invasive fungal infection that usually appears in the first days of life. Extremely low birth weight infants are the most frequently affected. Classic presentation includes diffuse extensive erythematous rash with papules, plaques, pustules and vesicles, which later undergoes desquamation.

Cannabidiol for the Treatment of Neonatal Hypoxic-Ischemic Brain Injury.

Each year, more than two million babies die or evolve to permanent invalidating sequelae worldwide because of Hypoxic-Ischemic Brain Injury (HIBI). There is no current treatment for that condition except for therapeutic hypothermia, which benefits only a select group of newborns. Preclinical studies offer solid evidence of the neuroprotective effects of Cannabidiol (CBD) when administered after diffuse or focal HI insults to newborn pigs and rodents.

Influence of Maternal Age and Gestational Age on Breast Milk Antioxidants During the First Month of Lactation.

Breast milk (BM) is beneficial due to its content in a wide range of different antioxidants, particularly relevant for preterm infants, who are at higher risk of oxidative stress. We hypothesize that BM antioxidants are adapted to gestational age and are negatively influenced by maternal age. Fifty breastfeeding women from two hospitals (Madrid, Spain) provided BM samples at days 7, 14 and 28 of lactation to assess total antioxidant capacity (ABTS), thiol groups, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase activities, lipid peroxidation (malondialdehyde, MDA + 4-Hydroxy-Trans-2-Nonenal, HNE), protein oxidation (carbonyl groups) (spectrophotometry) and melatonin (ELISA).

Cerebral blood flow velocity and oxygenation correlate predominantly with right ventricular function in cooled neonates with moderate-severe hypoxic-ischemic encephalopathy.

The relationship between right ventricular (RV) function and cerebral blood flow (CBF) velocity and cerebral oxygenation was assessed in neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH). Echocardiographic, transcranial Doppler, and hemodynamic data from 37 neonates with moderate-severe HIE + TH were reviewed. Twenty healthy newborns served as controls.

Cannabidiol Administration Prevents Hypoxia-Ischemia-Induced Hypomyelination in Newborn Rats.

Neonatal hypoxia-ischemia (HI) is a risk factor for myelination disturbances, a key factor for cerebral palsy. Cannabidiol (CBD) protects neurons and glial cells after HI insult in newborn animals. We hereby aimed to study CBD's effects on long-lasting HI-induced myelination deficits in newborn rats.

[Prostaglandin 12 analogs (epoprostenol and treprostinil) as a treatment for refractory bronchopulmonary dysplasia-induced pulmonary hypertension in an infant].

Pulmonary hypertension is a common complication of bronchopulmonary dysplasia, with a high mortality rate. Despite the high incidence of pulmonary hypertension, there are few available treatments. Epoprostenol and treprostinil are prostaglandin I2 analogs that activate adenylate cyclase and increase cyclic adenosine monophosphate in the pulmonary arterial smooth muscle cells.

Increased expression of cannabinoid CB and serotonin 5-HT heteroreceptor complexes in a model of newborn hypoxic-ischemic brain damage.

Preclinical work shows cannabidiol as a promising drug to manage neonatal hypoxic-ischemic brain damage (NHIBD). The molecular mechanism is not well defined but the beneficial effects of this phytocannabinoid are blocked by antagonists of both cannabinoid CB (CBR) and serotonin 5-HT (5-HT1AR) receptors that, in addition, may form heteromers in a heterologous expression system. Using bioluminescence energy transfer, we have shown a direct interaction of the two receptors that leads to a particular signaling in a heterologous system.