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.

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).

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.

Putative agmatinase inhibitor for hypoxic-ischemic new born brain damage.

Agmatine is an endogenous brain metabolite, decarboxylated arginine, which has neuroprotective properties when injected intraperitoneally (i.p.) into rat pups following hypoxic-ischemia.

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.

Repeated immobilization stress alters rat hippocampal and prefrontal cortical morphology in parallel with endogenous agmatine and arginine decarboxylase levels.

Agmatine, an endogenous amine derived from decarboxylation of L-arginine catalyzed by arginine decarboxylase, has been proposed as a neurotransmitter or neuromodulator in the brain. In the present study, we examined whether agmatine has neuroprotective effects against repeated immobilization-induced morphological changes in brain tissues and possible effects of immobilization stress on endogenous agmatine levels and arginine decarboxylase expression in rat brains. Sprague-Dawley rats were subjected to 2h immobilization stress daily for 7 days.

D-Amino acids in rat brain measured by liquid chromatography/tandem mass spectrometry.

Previous work has established that D-amino acids including D-serine (D-Ser) and D-aspartic acid (D-Asp) fulfill specific biological functions in the brain. In this work, the levels and anatomical distribution of d-amino acids in rat brain were determined by using an advantageous liquid chromatography/tandem mass spectrometric analytical method. The study was focused on D-Ser, D-Asp, and D-glutamic acid (D-Glu) because of the significance of L-Asp, L-Glu, and D-Ser in the nervous system.

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.

Assay of trace D-amino acids in neural tissue samples by capillary liquid chromatography/tandem mass spectrometry.

A sensitive chiral capillary HPLC-MS/MS method well suited for the determination of amino acid enantiomers in biological samples was developed. The method involved precolumn derivatization of the sample with 7-fluoro-4-nitrobenzoxadiazole (NBD-F). After derivatization, NBD-amino acids were stacked on a C18 reversed-phase extraction microcolumn, thus enriching and cleaning up the analytes.

N-tosyl-L-phenylalanyl-chloromethyl ketone reduces ceramide during hypoxic-ischemic brain injury in newborn rat.

N-tosyl-L-phenylalanyl-chloromethyl ketone (TPCK) suppresses apoptosis and protects neurons from damage in animal models. TPCK is thought to act by inhibiting ceramide production by sphingomyelinase. Ceramide is a proapoptotic intracellular signal that is involved in the cerebral ischemia.

Down-regulation of phospholipase D2 mRNA in neonatal rat brainstem and cerebellum after hypoxia-ischemia.

Phospholipase D (PLD) and phosphatidylcholine (PC) were implicated in apoptosis and cancer. However, direct evidence on the role of PLD in the cause of apoptosis remains obscure. It was recently reported that apoptosis and necrosis could be induced in the cerebellum and brainstem after focal cerebral hypoxic-ischemic (HI) injury.

Nicotinamide reduces hypoxic ischemic brain injury in the newborn rat.

Nicotinamide reduces ischemic brain injury in adult rats. Can similar brain protection be seen in newborn animals? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of 8% oxygen.

1-Benzyl-1,2,3,4-tetrahydroisoquinoline passes through the blood-brain barrier of rat brain: an in vivo microdialysis study.

Previous work has established that 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1-BnTIQ) causes a parkinsonian syndrome in rats. The present study reports the blood-brain barrier (BBB) permeability of 1-BnTIQ in freely moving rats with the aid of in vivo microdialysis-based measurements. The microdialysis probe was implanted in the frontal cortex of rat brain.

Agmatine reduces extracellular glutamate during pentylenetetrazole-induced seizures in rat brain: a potential mechanism for the anticonvulsive effects.

Glutamate has been implicated in the initiation and spread of seizure activity. Agmatine, an endogenous neuromodulator, is an antagonist of NMDA receptors and has anticonvulsive effects. Whether agmatine regulate glutamate release, as measured by in vivo microdialysis, is not known.

Grape seed extract suppresses lipid peroxidation and reduces hypoxic ischemic brain injury in neonatal rats.

Oxygen radicals play a crucial role in brain injury. Grape seed extract is a potent anti-oxidant. Does grape seed extract reduce brain injury in the rat pup? Seven-day-old rat pups had the right carotid arteries permanently ligated followed by 2.

Apoptosis and necrosis in developing cerebellum and brainstem induced after focal cerebral hypoxic-ischemic injury.

Focal cerebral hypoxia-ischemia due to isolated vascular insufficiency is well known to cause ipsilateral, but not contralateral, cerebral apoptosis. Hypoxic-ischemic damage to the cerebellum and brainstem in such a model has not been established. This experimental rodent study demonstrates, through deoxyribonucleic acid fragmentation and terminal deoxynucleotidyl transferase-mediated deoxyuridine 5'-triphosphate-digoxigenin nick end labeling analysis, that neuronal cells in these infratentorial regions also suffer mild apoptosis and necrosis after focal cerebral hypoxic-ischemic injury in the newborn rat.

Estrogen attenuates hypoxic-ischemic brain injury in neonatal rats.

Estrogen is neuroprotective in adult animals. We wished to determine if estrogen protects against brain injury in the newborn. Four-day-old rat pups were treated with subcutaneously implanted pellets containing 0.

Effect of agmatine on the time course of brain inflammatory cytokines after injury in rat pups.

Pro-inflammatory cytokines play an important role in brain injury. Agmatine reduces brain injury. Does agmatine act by reducing cytokines? Seven-day-old rat pups had the right carotid artery ligated and then were subjected to 2.

Treatment with tamoxifen reduces hypoxic-ischemic brain injury in neonatal rats.

Tamoxifen, an estrogen receptor modulator, is neuroprotective in adult rats. Does tamoxifen reduce brain injury in the rat pup? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of hypoxia (8% oxygen).

Inhibiting caspase-8 after injury reduces hypoxic-ischemic brain injury in the newborn rat.

A broad spectrum caspase inhibitor reduces brain injury. Will a caspase-8 inhibitor provide protection? Seven-day-old rat pups had the right carotid artery ligated, then were subjected to 2.5 h of 8% oxygen.