Intranasal insulin attenuates hypoxia-ischemia-induced short-term sensorimotor behavioral disturbances, neuronal apoptosis, and brain damage in neonatal rats.

There is a significant need for additional therapy to improve outcomes for newborns with acute Hypoxic-ischemic (HI) encephalopathy (HIE). New evidence suggests that insulin could be neuroprotective. This study aimed to investigate whether intranasal insulin attenuates HI-induced brain damage and neurobehavioral dysfunction in neonatal rats.

Intrauterine growth restriction and neonatal hypoxic ischemic brain injury causes sex-specific long-term neurobehavioral abnormalities in rats.

There is a lack of knowledge of factors preventing an adequate response to moderate hypothermia after hypoxic ischemic (HI) brain injury. We hypothesized that growth restriction from reduced intrauterine perfusion would predispose neonatal rats to have a worse outcome with HI brain injury. IUGR was induced by placental insufficiency in dams at 14 days of gestation.

Neuroprotective Effects of Intranasal IGF-1 against Neonatal Lipopolysaccharide-Induced Neurobehavioral Deficits and Neuronal Inflammation in the Substantia Nigra and Locus Coeruleus of Juvenile Rats.

Neonatal lipopolysaccharide (LPS) exposure-induced brain inflammation resulted in motor dysfunction and brain dopaminergic neuronal injury, and increased the risks of neurodegenerative disorders in adult rats. Our previous studies showed that intranasal administration of insulin-like growth factor-1 (IGF-1) protects against LPS-induced white matter injury in the developing rat brain. To further examine whether IGF-1 protects against LPS-induced brain neuronal injury and neurobehavioral dysfunction, recombinant human IGF-1 (rhIGF-1) at a dose of 50 µg/pup was administered intranasally 1 h following intracerebral injection of LPS (1 mg/kg) in postnatal day 5 (P5) Sprague-Dawley rat pups.

Early Postnatal Lipopolysaccharide Exposure Leads to Enhanced Neurogenesis and Impaired Communicative Functions in Rats.

Perinatal infection is a well-identified risk factor for a number of neurodevelopmental disorders, including brain white matter injury (WMI) and Autism Spectrum Disorders (ASD). The underlying mechanisms by which early life inflammatory events cause aberrant neural, cytoarchitectural, and network organization, remain elusive. This study is aimed to investigate how systemic lipopolysaccharide (LPS)-induced neuroinflammation affects microglia phenotypes and early neural developmental events in rats.

Erythropoietin Ameliorates Neonatal Hypoxia-Ischemia-Induced Neurobehavioral Deficits, Neuroinflammation, and Hippocampal Injury in the Juvenile Rat.

The hematopoietic growth factor erythropoietin (EPO) has been shown to be neuroprotective against hypoxia-ischemia (HI) in Postnatal Day 7 (P7)-P10 or adult animal models. The current study was aimed to determine whether EPO also provides long-lasting neuroprotection against HI in P5 rats, which is relevant to immature human infants. Sprague-Dawley rats at P5 were subjected to right common carotid artery ligation followed by an exposure to 6% oxygen with balanced nitrogen for 1.

Corticosteroid responses following hypoxic preconditioning provide neuroprotection against subsequent hypoxic-ischemic brain injury in the newborn rats.

Limited research has evaluated the corticosteroids (CS) response in hypoxic preconditioning (PC) induced neuroprotection against subsequent hypoxic-ischemic (HI) brain injury in newborns. To measure, CS response to hypoxic PC, at postnatal day 6 (P6), rat pups were randomly divided into sham, NoPC (exposure to 21% O2) and PC (exposure to 8% O2 for 3h) groups. In a separate experiment, at P6, rat pups were randomly divided into three groups (sham, NoPC+HI, PC+HI).

Interleukin-1 receptor antagonist reduces neonatal lipopolysaccharide-induced long-lasting neurobehavioral deficits and dopaminergic neuronal injury in adult rats.

Our previous study showed that a single lipopolysaccharide (LPS) treatment to neonatal rats could induce a long-lasting neuroinflammatory response and dopaminergic system injury late in life. This is evidenced by a sustained activation of microglia and elevated interleukin-1β (IL-1β) levels, as well as reduced tyrosine hydroxylase (TH) expression in the substantia nigra (SN) of P70 rat brain. The object of the current study was to test whether co-administration of IL-1 receptor antagonist (IL-1ra) protects against LPS-induced neurological dysfunction later in life.

IL-1 receptor antagonist attenuates neonatal lipopolysaccharide-induced long-lasting learning impairment and hippocampal injury in adult rats.

We have previously reported that neonatal lipopolysaccharide (LPS) exposure resulted in an increase in interleukin-1β (IL-1β) content, injury to the hippocampus, and cognitive deficits in juvenile male and female rats, as well as female adult rats. The present study aimed to determine whether an anti-inflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra), protects against the neonatal LPS exposure-induced inflammatory responses, hippocampal injury, and long-lasting learning deficits in adult rats. LPS (1 mg/kg) or LPS plus IL-1ra (0.

Dexamethasone but not the equivalent doses of hydrocortisone induces neurotoxicity in neonatal rat brain.

Background: The use of dexamethasone (Dex) in premature infants to treat or prevent chronic lung disease adversely affects neurodevelopment. Recent clinical studies suggest that hydrocortisone (HC) is a safer alternative to Dex. We compared the effects of Dex and HC on neurotoxicity in newborn rats.

Dexamethasone-induced neuroprotection in hypoxic-ischemic brain injury in newborn rats is partly mediated via Akt activation.

Prior treatment with dexamethasone (Dex) provides neuroprotection against hypoxia ischemia (HI) in newborn rats. Recent studies have shown that the phosphatidylinositol-3-kinase/Akt (PI3K/Akt) pathway plays an important role in the neuroprotection. The objective of this study is to evaluate the role of the PI3K/Akt pathway in the Dex-induced neuroprotection against subsequent HI brain injury.

Dexamethasone decreases insulin-like growth factor-I and -II via a glucocorticoid receptor dependent mechanism in developing rat brain.

Objectives: Dexamethasone (Dex) causes neurodegeneration in developing brain. Insulin-like growth factor-I (IGF-I) and -II (IGF-II) are potent neurotrophic and differentiation factors and play key roles in the regulation of growth and development of CNS. Current project evaluated the effects of Dex on IGF-I and -II in developing rat brains.

Dexamethasone induces apoptosis of progenitor cells in the subventricular zone and dentate gyrus of developing rat brain.

The use of dexamethasone in premature infants to prevent and/or treat bronchopulmonary dysplasia adversely affects neurocognitive development and is associated with cerebral palsy. The underlying mechanisms of these effects are multifactorial and likely include apoptosis. The objective of this study was to confirm whether dexamethasone causes apoptosis in different regions of the developing rat brain.

Neonatal exposure to lipopolysaccharide enhances accumulation of α-synuclein aggregation and dopamine transporter protein expression in the substantia nigra in responses to rotenone challenge in later life.

Brain inflammation in early life may enhance adult susceptibility to develop neurodegenerative disorders triggered by environmental toxins. Our previous studies show that perinatal lipopolysaccharide (LPS) exposure enhances adult susceptibility to rotenone-induced injury to the dopaminergic system in the substantia nigra (SN) of the adult rat brain. To further investigate the enhanced adult susceptibility by neonatal LPS exposure to rotenone neurotoxicity, we used our neonatal rat model of LPS exposure (1mg/kg, intracerebral injection in postnatal day 5, P5, neonatal rats) to examine the protein levels of α-synuclein and dopamine transporters (DAT) in the adult rat.

Celecoxib reduces brain dopaminergic neuronaldysfunction, and improves sensorimotor behavioral performance in neonatal rats exposed to systemic lipopolysaccharide.

Background: Cyclooxygenase-2 (COX-2) is induced in inflammatory cells in response to cytokines and pro-inflammatory molecules, suggesting that COX-2 has a role in the inflammatory process. The objective of the current study was to examine whether celecoxib, a selective COX-2 inhibitor, could ameliorate lipopolysaccharide (LPS)-induced brain inflammation, dopaminergic neuronal dysfunction and sensorimotor behavioral impairments.

Methods: Intraperitoneal (i.

Hypoxic preconditioning provides neuroprotection and increases vascular endothelial growth factor A, preserves the phosphorylation of Akt-Ser-473 and diminishes the increase in caspase-3 activity in neonatal rat hypoxic-ischemic model.

Vascular endothelial growth factor A (VEGF) likely plays a role in the hypoxic preconditioning (PC) induced tolerance to subsequent hypoxic-ischemic (HI) injury to the brain. However, limited data is available concerning VEGF in the developing brain after HI following PC. Neuroprotection by VEGF involves activation of Akt which inhibits apoptotic processes that contribute significantly to the brain injury in neonatal HI.

Neuroprotective effects of vascular endothelial growth factor following hypoxic ischemic brain injury in neonatal rats.

Vascular Endothelial Growth Factor (VEGF) protects the brain against ischemic injury in adult animals. We evaluated whether VEGF has neuroprotective effects against hypoxic-ischemic (HI) brain injury in newborn rats. Seven-day-old rat pups had the right carotid artery permanently ligated followed by 140 min of hypoxia (8% oxygen).

Neuroprotective effects of sodium orthovanadate after hypoxic-ischemic brain injury in neonatal rats.

Sodium orthovanadate (SOV), a competitive inhibitor of protein tyrosine phosphatases, is neuroprotective in adult animals following an ischemic event. The present study evaluated whether SOV might be protective in a rat pup hypoxic-ischemic (HI) model. Seven-day-old rat pups had the right carotid artery permanently ligated followed by 140 min of hypoxia (8% oxygen).

Grape seed extract given three hours after injury suppresses lipid peroxidation and reduces hypoxic-ischemic brain injury in neonatal rats.

We have reported that pretreatment with grape seed extract (GSE), a potent antioxidant, is neuroprotective. This study examined whether treatment after injury with GSE is protective. Seven-day-old rat pups had the right carotid artery ligated, and then 2.