Limits...
Combination treatment with ethyl pyruvate and IGF-I exerts neuroprotective effects against brain injury in a rat model of neonatal hypoxic-ischemic encephalopathy.

Rong Z, Pan R, Chang L, Lee W - Int. J. Mol. Med. (2015)

Bottom Line: Under conditions of OGD, the LDH levels increased and neuronal viability decreased.Treatment with 0.5 mM EP or 25 ng/ml IGF‑I protected the neurons (P<0.05), exerting additive effects.This effect may be the result of reduced neuronal injury, and enhanced neurogenesis and maturation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

ABSTRACT
Neonatal hypoxic-ischemic (HI) brain injury causes severe brain damage in newborns. Following HI injury, rapidly accumulating oxidants injure neurons and interrupt ongoing developmental processes. The antioxidant, sodium pyruvate, has been shown to reduce neuronal injury in neonatal rats under conditions of oxygen glucose deprivation (OGD) and HI injury. In this study, we evaluated the effects of ethyl pyruvate (EP) and insulin‑like growth factor‑I (IGF‑I) alone or in combination in a similar setting. For this purpose, we used an in vitro model involving primary neonatal rat cortical neurons subjected to OGD for 2.5 h and an in vivo model involving unilateral carotid ligation in rats on post-natal day 7 with exposure to 8% hypoxia for 2.5 h. The cultured neurons were examined by lactate dehydrogenase (LDH) and cell viability assays. For the in vivo experiments, behavioral development was evaluated by the foot fault test at 4 weeks of recovery. 2,3,5‑Triphenyltetrazolium chloride monohydrate and cresyl violet staining were used to evaluate HI injury. The injured neurons were Fluoro‑Jade B-labeled, new neuroprecursors were double labeled with bromodeoxyuridine (BrdU) and doublecortin, new mature neurons were BrdU-labeled and neuronal nuclei were labeled by immunofluorescence. Under conditions of OGD, the LDH levels increased and neuronal viability decreased. Treatment with 0.5 mM EP or 25 ng/ml IGF‑I protected the neurons (P<0.05), exerting additive effects. Similarly, either the early administration of EP or delayed treatment with IGF‑I protected the neonatal rat brains against HI injury and improved neurological performance and these effects were also additive. This effect may be the result of reduced neuronal injury, and enhanced neurogenesis and maturation. On the whole, our findings demonstrate that the combination of the early administration of EP with delayed treatment with IGF‑I exerts neuroprotective effects against HI injury in neonatal rat brains.

No MeSH data available.


Related in: MedlinePlus

Ethyl pyruvate (EP) and insulin-like growth factor-I (IGF-I) promote long-term behavioral development following hypoxic-ischemic (HI) injury. (A) EP exerted neuroprotective effects in a dose-dependent manner (30 min after HI injury) *P<0.05 as indicated (n=6). (B) Body weight following HI injury. Rat pups were treated with EP 30 min after HI injury or with IGF-I 24 h after HI injury or with both agents. The y-axis represents the percentage changes in body weight as compared to the weight before HI injury. *P<0.05 compared with the sham-operated group, #P<0.05 compared with other the 3 groups subjected to HI injury (n=8). Foot fault tests were performed at 4 weeks of recovery (P35). Number of foot faults of (C) right forelimbs or (D) right hindlimbs per 50 steps were counted within 5 min. *P<0.05 compared with sham-operated group, #P<0.05 compared with other 3 groups subjected to HI injury (n=8). L, left; R, right.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4494588&req=5

f2-ijmm-36-01-0195: Ethyl pyruvate (EP) and insulin-like growth factor-I (IGF-I) promote long-term behavioral development following hypoxic-ischemic (HI) injury. (A) EP exerted neuroprotective effects in a dose-dependent manner (30 min after HI injury) *P<0.05 as indicated (n=6). (B) Body weight following HI injury. Rat pups were treated with EP 30 min after HI injury or with IGF-I 24 h after HI injury or with both agents. The y-axis represents the percentage changes in body weight as compared to the weight before HI injury. *P<0.05 compared with the sham-operated group, #P<0.05 compared with other the 3 groups subjected to HI injury (n=8). Foot fault tests were performed at 4 weeks of recovery (P35). Number of foot faults of (C) right forelimbs or (D) right hindlimbs per 50 steps were counted within 5 min. *P<0.05 compared with sham-operated group, #P<0.05 compared with other 3 groups subjected to HI injury (n=8). L, left; R, right.

Mentions: We then evaluated the neuroprotective effects of EP and/or IGF-I in a commonly used neonatal rat model of HI injury (18). At 48 h of recovery, EP began to show protective effects against HI injury at the dose of 25 mg/kg (administered at 30 min after HI injury), indicated by an increase in the volume area of surviving brain tissue (Fig. 2A). We selected a previously published IGF-I (3 mg/kg, 24 h post HI) treatment dose and schedule (19) to evaluate the neuroprotective effects of the two treatments.


Combination treatment with ethyl pyruvate and IGF-I exerts neuroprotective effects against brain injury in a rat model of neonatal hypoxic-ischemic encephalopathy.

Rong Z, Pan R, Chang L, Lee W - Int. J. Mol. Med. (2015)

Ethyl pyruvate (EP) and insulin-like growth factor-I (IGF-I) promote long-term behavioral development following hypoxic-ischemic (HI) injury. (A) EP exerted neuroprotective effects in a dose-dependent manner (30 min after HI injury) *P<0.05 as indicated (n=6). (B) Body weight following HI injury. Rat pups were treated with EP 30 min after HI injury or with IGF-I 24 h after HI injury or with both agents. The y-axis represents the percentage changes in body weight as compared to the weight before HI injury. *P<0.05 compared with the sham-operated group, #P<0.05 compared with other the 3 groups subjected to HI injury (n=8). Foot fault tests were performed at 4 weeks of recovery (P35). Number of foot faults of (C) right forelimbs or (D) right hindlimbs per 50 steps were counted within 5 min. *P<0.05 compared with sham-operated group, #P<0.05 compared with other 3 groups subjected to HI injury (n=8). L, left; R, right.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494588&req=5

f2-ijmm-36-01-0195: Ethyl pyruvate (EP) and insulin-like growth factor-I (IGF-I) promote long-term behavioral development following hypoxic-ischemic (HI) injury. (A) EP exerted neuroprotective effects in a dose-dependent manner (30 min after HI injury) *P<0.05 as indicated (n=6). (B) Body weight following HI injury. Rat pups were treated with EP 30 min after HI injury or with IGF-I 24 h after HI injury or with both agents. The y-axis represents the percentage changes in body weight as compared to the weight before HI injury. *P<0.05 compared with the sham-operated group, #P<0.05 compared with other the 3 groups subjected to HI injury (n=8). Foot fault tests were performed at 4 weeks of recovery (P35). Number of foot faults of (C) right forelimbs or (D) right hindlimbs per 50 steps were counted within 5 min. *P<0.05 compared with sham-operated group, #P<0.05 compared with other 3 groups subjected to HI injury (n=8). L, left; R, right.
Mentions: We then evaluated the neuroprotective effects of EP and/or IGF-I in a commonly used neonatal rat model of HI injury (18). At 48 h of recovery, EP began to show protective effects against HI injury at the dose of 25 mg/kg (administered at 30 min after HI injury), indicated by an increase in the volume area of surviving brain tissue (Fig. 2A). We selected a previously published IGF-I (3 mg/kg, 24 h post HI) treatment dose and schedule (19) to evaluate the neuroprotective effects of the two treatments.

Bottom Line: Under conditions of OGD, the LDH levels increased and neuronal viability decreased.Treatment with 0.5 mM EP or 25 ng/ml IGF‑I protected the neurons (P<0.05), exerting additive effects.This effect may be the result of reduced neuronal injury, and enhanced neurogenesis and maturation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

ABSTRACT
Neonatal hypoxic-ischemic (HI) brain injury causes severe brain damage in newborns. Following HI injury, rapidly accumulating oxidants injure neurons and interrupt ongoing developmental processes. The antioxidant, sodium pyruvate, has been shown to reduce neuronal injury in neonatal rats under conditions of oxygen glucose deprivation (OGD) and HI injury. In this study, we evaluated the effects of ethyl pyruvate (EP) and insulin‑like growth factor‑I (IGF‑I) alone or in combination in a similar setting. For this purpose, we used an in vitro model involving primary neonatal rat cortical neurons subjected to OGD for 2.5 h and an in vivo model involving unilateral carotid ligation in rats on post-natal day 7 with exposure to 8% hypoxia for 2.5 h. The cultured neurons were examined by lactate dehydrogenase (LDH) and cell viability assays. For the in vivo experiments, behavioral development was evaluated by the foot fault test at 4 weeks of recovery. 2,3,5‑Triphenyltetrazolium chloride monohydrate and cresyl violet staining were used to evaluate HI injury. The injured neurons were Fluoro‑Jade B-labeled, new neuroprecursors were double labeled with bromodeoxyuridine (BrdU) and doublecortin, new mature neurons were BrdU-labeled and neuronal nuclei were labeled by immunofluorescence. Under conditions of OGD, the LDH levels increased and neuronal viability decreased. Treatment with 0.5 mM EP or 25 ng/ml IGF‑I protected the neurons (P<0.05), exerting additive effects. Similarly, either the early administration of EP or delayed treatment with IGF‑I protected the neonatal rat brains against HI injury and improved neurological performance and these effects were also additive. This effect may be the result of reduced neuronal injury, and enhanced neurogenesis and maturation. On the whole, our findings demonstrate that the combination of the early administration of EP with delayed treatment with IGF‑I exerts neuroprotective effects against HI injury in neonatal rat brains.

No MeSH data available.


Related in: MedlinePlus