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Pretreatment with Resveratrol Prevents Neuronal Injury and Cognitive Deficits Induced by Perinatal Hypoxia-Ischemia in Rats.

Arteaga O, Revuelta M, Urigüen L, Álvarez A, Montalvo H, Hilario E - PLoS ONE (2015)

Bottom Line: Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response.Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood.We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology & Histology, School of Medicine & Dentistry, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.

ABSTRACT
Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia.

No MeSH data available.


Related in: MedlinePlus

Analysis of mitochondrial transmembrane potential by Rhodamine 123 in suspension of acutely isolated cells.Percentage of cells labeled with the in vivo marker Rh 123 at different time points after hypoxia-ischemia: (A) 0 h, (B) 3 h and (C) 12 h. Relative fluorescence intensity of cells exhibiting Rh 123 fluorescence at different time points after hypoxia-ischemia: (D) 0 h, (E) 3 h and (F) 12 h, in control (n≥5), HI (n≥5) and animals pretreated with resveratrol (n≥5) groups. Asterisks denote the significance levels when compared to the control group (***P<0.0001 or *P<0.05). The hash symbols denote the significance levels when compared to the HI group (##P<0.005 or #P<0.05).
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pone.0142424.g008: Analysis of mitochondrial transmembrane potential by Rhodamine 123 in suspension of acutely isolated cells.Percentage of cells labeled with the in vivo marker Rh 123 at different time points after hypoxia-ischemia: (A) 0 h, (B) 3 h and (C) 12 h. Relative fluorescence intensity of cells exhibiting Rh 123 fluorescence at different time points after hypoxia-ischemia: (D) 0 h, (E) 3 h and (F) 12 h, in control (n≥5), HI (n≥5) and animals pretreated with resveratrol (n≥5) groups. Asterisks denote the significance levels when compared to the control group (***P<0.0001 or *P<0.05). The hash symbols denote the significance levels when compared to the HI group (##P<0.005 or #P<0.05).

Mentions: Mitochondrial transmembrane potential was analyzed using the fluorochrome Rhodamine 123. At 0 h ([F(2,19) = 10.8, P < 0.005]), hypoxia-ischemia generated a decrease in the percentage of Rh 123 positive cells (82.89±3.78%), in comparison to the control group (98.14±0.47%). In contrast, the RVT-b group showed a percentage of Rh 123 positive cells (93.25±1.18%) which was similar to that of the control group (Fig 8A). At 3 h ([F(2,12) = 6.84, P < 0.05]), the number of Rh 123 positive cells diminished in HI animals (91.99±2.28), and also in the resveratrol pretreated group (92.91±1.71%). Although these reductions were statistically significant, they were not as evident as the differences at 0 h with respect to control (99.88±0.03%) (Fig 8B). However, at 12 h ([F(2,24) = 28.02, P < 0.0001]) animals subjected to the hypoxic-ischemic event underwent again an important diminishment in the percentage of Rh 123 positive cells (76.08±3.91%) in comparison to the control group (98.81±0.37%), while animals pretreated with resveratrol showed similar values (90.39±1.59%) to those of the controls (Fig 8C).


Pretreatment with Resveratrol Prevents Neuronal Injury and Cognitive Deficits Induced by Perinatal Hypoxia-Ischemia in Rats.

Arteaga O, Revuelta M, Urigüen L, Álvarez A, Montalvo H, Hilario E - PLoS ONE (2015)

Analysis of mitochondrial transmembrane potential by Rhodamine 123 in suspension of acutely isolated cells.Percentage of cells labeled with the in vivo marker Rh 123 at different time points after hypoxia-ischemia: (A) 0 h, (B) 3 h and (C) 12 h. Relative fluorescence intensity of cells exhibiting Rh 123 fluorescence at different time points after hypoxia-ischemia: (D) 0 h, (E) 3 h and (F) 12 h, in control (n≥5), HI (n≥5) and animals pretreated with resveratrol (n≥5) groups. Asterisks denote the significance levels when compared to the control group (***P<0.0001 or *P<0.05). The hash symbols denote the significance levels when compared to the HI group (##P<0.005 or #P<0.05).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4636303&req=5

pone.0142424.g008: Analysis of mitochondrial transmembrane potential by Rhodamine 123 in suspension of acutely isolated cells.Percentage of cells labeled with the in vivo marker Rh 123 at different time points after hypoxia-ischemia: (A) 0 h, (B) 3 h and (C) 12 h. Relative fluorescence intensity of cells exhibiting Rh 123 fluorescence at different time points after hypoxia-ischemia: (D) 0 h, (E) 3 h and (F) 12 h, in control (n≥5), HI (n≥5) and animals pretreated with resveratrol (n≥5) groups. Asterisks denote the significance levels when compared to the control group (***P<0.0001 or *P<0.05). The hash symbols denote the significance levels when compared to the HI group (##P<0.005 or #P<0.05).
Mentions: Mitochondrial transmembrane potential was analyzed using the fluorochrome Rhodamine 123. At 0 h ([F(2,19) = 10.8, P < 0.005]), hypoxia-ischemia generated a decrease in the percentage of Rh 123 positive cells (82.89±3.78%), in comparison to the control group (98.14±0.47%). In contrast, the RVT-b group showed a percentage of Rh 123 positive cells (93.25±1.18%) which was similar to that of the control group (Fig 8A). At 3 h ([F(2,12) = 6.84, P < 0.05]), the number of Rh 123 positive cells diminished in HI animals (91.99±2.28), and also in the resveratrol pretreated group (92.91±1.71%). Although these reductions were statistically significant, they were not as evident as the differences at 0 h with respect to control (99.88±0.03%) (Fig 8B). However, at 12 h ([F(2,24) = 28.02, P < 0.0001]) animals subjected to the hypoxic-ischemic event underwent again an important diminishment in the percentage of Rh 123 positive cells (76.08±3.91%) in comparison to the control group (98.81±0.37%), while animals pretreated with resveratrol showed similar values (90.39±1.59%) to those of the controls (Fig 8C).

Bottom Line: Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response.Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood.We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology & Histology, School of Medicine & Dentistry, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.

ABSTRACT
Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia.

No MeSH data available.


Related in: MedlinePlus