Early-life fluoxetine exposure reduced functional deficits after hypoxic–ischemia brain injury in rat pups☆

Chang, Ying-Chao; Tzeng, Shun-Fen; Yu, Lung; Huang, A‐Min; Lee, Hsueh-Te; Huang, Chao-Ching; Ho, Chien-Jung

doi:10.1016/j.nbd.2006.06.001

Cited by 51 publications

(32 citation statements)

References 59 publications

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“…Sparing neurons from pathologic damage may not necessarily translate into sparing them from dysfunction. Therefore, both pathologic and behavioral outcome assessments are important for evaluating the efficacy of potential treatments that may mitigate the consequences of brain insult (20). This study presents the first evidence showing long-term outcomes, at both the behavioral and pathologic levels, of LPS preconditioning against HI in neonatal rats.…”

Section: Discussionmentioning

confidence: 85%

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Lipopolysaccharide Preconditioning Reduces Neuroinflammation Against Hypoxic Ischemia and Provides Long-Term Outcome of Neuroprotection in Neonatal Rat

2009

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Hypoxic ischemia (HI) in newborns causes long-term neurologic abnormalities. Systemic lipopolysaccharide (LPS) is neuroprotective in neonatal rats when injected 24 h before HI. However, the effect on HI-induced neuroinflammation and the long-term outcome of LPS preconditioning in neonatal rats have not been examined. In a rat-pup HI model, compared with normal saline (NS), 0.3 mg/kg of LPS injected 24 h before HI greatly increased microglial cell and macrophage activation and up-regulated TNF-alpha and inducible NOS expression 12-h postinjection and resulted in high mortality during HI. In contrast, 0.05 mg/kg of LPS elicited very little microglia and macrophage activation and TNF-alpha and inducible NOS expression and resulted in low mortality. Given 24 h before HI, low-dose (0.05 mg/kg) LPS greatly reduced microglia and macrophage activation, TNF-alpha expression, and reactive oxygen species production 24-h post-HI compared with NS-treated rats. Rats in the low-dose LPS group also showed significantly better learning and memory and less brain damage in adulthood. Learning and memory performance among the LPS-HI, LPS, and NS groups was not significantly different. We conclude that low-dose LPS preconditioning in neonatal rats greatly reduces HI-induced neuroinflammation and provides long-term neuroprotection against behavioral and pathologic abnormalities. T wenty percent of newborns with hypoxic ischemia (HI) die and an additional 25% have long-term neurodevelopmental handicaps (1). Although hypothermia has been used to treat newborns with HI encephalopathy, there is no effective pharmacological therapy. Sublethal lipopolysaccharide (LPS) stimulation, preconditioning, protects against subsequent lethal injury. Elucidating the neuroprotective mechanisms of LPS preconditioning may offer potential therapies against HI brain injury (2,3).Systemic LPS preconditioning (0.5 to 0.9 mg/kg) 48 to 72 h before ischemic insults protected adult rats against cerebral ischemia (4,5). LPS (0.3 or 1 mg/kg) sensitized neonatal Wistar rats and worsened HI brain injury when given 4, 6, or 72 h before HI (6). In contrast, 0.3 mg/kg of LPS 24 h before HI protected them (7,8). There are several neuroprotective preconditioning models for the neonatal brain (7,9 -13), but there are only few evaluations of long-term outcomes of LPS preconditioning at behavioral and pathologic levels.Inflammatory responses are important for developing neonatal HI brain injury (1). Up-regulated reactive oxygen species (ROS) production is also critical in inducing HI damage in the neonatal brain (1,14). One study (15) of adult rats showed that low-dose (0.05 mg/kg) LPS pretreatment 24 h before transient middle-cerebral-artery occlusion decreased ischemic infarct size despite increases of inflammatory cells in the ischemic hemisphere. In contrast, another study (16) suggested that LPS (0.2 mg/kg) preconditioning 48 h before transient middlecerebral-artery occlusion suppressed neuroinflammatory responses. Although up-regulating endogenous corticost...

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Section: Discussionmentioning

confidence: 85%

“…Rats underwent the water maze, as previously described (12,20). In brief, the pool was divided into four quadrants.…”

Section: Methodsmentioning

confidence: 99%

Lipopolysaccharide Preconditioning Reduces Neuroinflammation Against Hypoxic Ischemia and Provides Long-Term Outcome of Neuroprotection in Neonatal Rat

2009

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“…HP and CoCl 2 preconditioning were able to reduce the extent of cortical injury and only HP reduced striatal damage. Although many treatments have been tested in the HI model at short term intervals, only a few have been examined and found to yield long-term functional outcomes (3,16,26,27). Using preconditioning with hypoxia and two hypoxia-mimetic compounds, CoCl 2 and DFX, we observed long-term protective actions of these treatment strategies.…”

Section: Discussionmentioning

confidence: 91%

Long-Term Functional and Protective Actions of Preconditioning With Hypoxia, Cobalt Chloride, and Desferrioxamine Against Hypoxic-Ischemic Injury in Neonatal Rats

et al. 2008

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ABSTRACT:Preconditioning with hypoxia and hypoxia-mimetic compounds cobalt chloride (CoCl 2 ) and desferrioxamine (DFX) protects against hypoxic-ischemic (HI) injury in neonatal rat brain. We examined long-term functional and protective actions of preconditioning induced by hypoxia, CoCl 2 and DFX in a neonatal rat model of HI. Postnatal day six rat pups were exposed to preconditioning with hypoxia (8% oxygen) or injections of CoCl 2 , DFX or saline vehicle and 24 h later rats underwent HI or sham surgery. Behavioral tests were performed and at the conclusion of experiments, brains removed for morphologic analyses. HI resulted in a large unilateral lesion in the ipsilateral hemisphere compared with sham control rats. All preconditioning treatments significantly reduced the total lesion volume. Behavioral deficits were observed in HI rats compared with sham controls. The reduction in forelimb grasping strength in HI rats was attenuated by preconditioning with hypoxia, CoCl 2 and DFX. HI increased the number of foot faults in a grid-walking test and resulted in forelimb asymmetry in the cylinder test. Only preconditioning with hypoxia reversed all three functional deficits after HI. These findings indicate that preconditioning, especially when induced by hypoxia, has the potential to minimize the morphologic and functional effects of neonatal HI injury. (Pediatr Res 63: 620-624, 2008)

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“…In neonatal brains hypoxia-ischemia has been shown to either increase or decrease hippocampal precursor cell survival (Bartley et al, 2005;Chang et al, 2006). It is known that endogenous neurogenesis can be modulated by various extrinsic and intrinsic factors.…”

Section: Introductionmentioning

confidence: 99%

Neurogenesis and neuronal commitment following ischemia in a new mouse model for neonatal stroke

et al. 2008

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Stroke in the neonatal brain is an important cause of neurologic morbidity. To characterize the dynamics of neural progenitor cell proliferation and maturation after survival delays in the neonatal brain following ischemia, we utilized unilateral carotid ligation alone to produce infarcts in postnatal day 12 CD1 mice. We investigated the neurogenesis derived from the sub-ventricular zone and the sub-granular zone of the dentate gyrus subsequent to injury. Newly produced cells were labeled by bromodeoxyuridine at ~1week (P18-20) after the insult by 5 I.P. injections (each 50mg/kg). Subsequent migration and differentiation of the newborn cells was investigated at postnatal day 40 by immunohistochemistry for molecular neuronal and glial cell-lineage markers and BrdU incorporation. Cresyl violet stain demonstrated massive loss of neurons in the ipsilateral septal hippocampus in the CA3 and CA1 regions associated with atrophy. Total counts of new cells were significantly lowered not only in the ipsilateral injured but also the contralateral uninjured hippocampi and correlated with the lesion induced atrophy. Bilateral percent neuronal commitments in the dentate gyri however, were not significantly different from control. New cell densities in the neocortex and striatum increased bilaterally after neonatal stroke. The predominantly non-neuronal commitment of the SVZ derived new cells was similar to the percentage of non-neuronal commitment in controls. In conclusion, neurogenesis occurring at 1 week after neonatal ischemia in the model maintained cell-lineage commitment patterns similar to sham controls. However, the total number of hippocampal SGZ-derived new neurons was reduced bilaterally; in contrast, the SVZ-derived neurogenesis was amplified.

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Early-life fluoxetine exposure reduced functional deficits after hypoxic–ischemia brain injury in rat pups☆

Cited by 51 publications

References 59 publications

Lipopolysaccharide Preconditioning Reduces Neuroinflammation Against Hypoxic Ischemia and Provides Long-Term Outcome of Neuroprotection in Neonatal Rat

Lipopolysaccharide Preconditioning Reduces Neuroinflammation Against Hypoxic Ischemia and Provides Long-Term Outcome of Neuroprotection in Neonatal Rat

Long-Term Functional and Protective Actions of Preconditioning With Hypoxia, Cobalt Chloride, and Desferrioxamine Against Hypoxic-Ischemic Injury in Neonatal Rats

Neurogenesis and neuronal commitment following ischemia in a new mouse model for neonatal stroke

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