Neuroprotective effects of spermine following hypoxic-ishemic-induced brain damage: A mechanistic study

A Clarkson, H Liu, L Pearson, M Kapoor, JC Harrison, IA Sammut, David Jackson, I Appleton

Research output: Contribution to journalArticle

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Abstract

The polyamines (spermine, putrescine, and spermidine) can have neurotoxic or neuroprotective properties in models of neurodegeneration. However, assessment in a model of hypoxia'ischemia (HI) has not been defined. Furthermore, the putative mechanisms of neuroprotection have not been elucidated. Therefore, the present study examined the effects of the polyamines in a rat pup model of HI and determined effects on key enzymes involved in inflammation, namely, nitric oxide synthase (NOS) and arginase. In addition, effects on mitochondrial function were investigated. The polyamines or saline were administered i.p. at 10mg/kg/day for 6 days post-HI. Histological assessment 7 days post-HI revealed that only spermine significantly (P<0.01) reduced infarct size from 46.14 ± 10.4mm3 (HI + saline) to 4.9 ± 2.7 mm3. NOS activity was significantly increased following spermine treatment in the left (ligated) hemisphere compared with nonintervention controls (P<0.01) and HI + saline (P<0.05). In contrast, spermine decreased arginase activity compared with HI + saline but was still significantly elevated in comparison to nonintervention controls (P<0.01). Assessment of mitochondrial function in the HI + saline group, revealed significant and extensive damage to complex-I (P<0.01) and IV (P<0.001) and loss of citrate synthase activity (P<0.05). No effect on complex II-III was observed. Spermine treatment significantly prevented all these effects. This study has therefore confirmed the neuroprotective effects of spermine in vivo. However, for the first time, we have shown that this effect may, in part, be due to increased NOS activity and preservation of mitochondrial function.
Original languageEnglish
Pages (from-to)1114-1116
Number of pages3
JournalFASEB Journal
Volume18
Issue number10
DOIs
Publication statusPublished - 2005

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Putrescine
Spermidine
Neuroprotective Agents
Brain
Ischemia
Polyamines
Nitric Oxide Synthase
Arginase
Citrate (si)-Synthase
Spermine
Rats
Hypoxia
Enzymes
Inflammation

Cite this

Clarkson, A., Liu, H., Pearson, L., Kapoor, M., Harrison, JC., Sammut, IA., ... Appleton, I. (2005). Neuroprotective effects of spermine following hypoxic-ishemic-induced brain damage: A mechanistic study. FASEB Journal, 18(10), 1114-1116. https://doi.org/10.1096/fj.03-1203fje
Clarkson, A ; Liu, H ; Pearson, L ; Kapoor, M ; Harrison, JC ; Sammut, IA ; Jackson, David ; Appleton, I. / Neuroprotective effects of spermine following hypoxic-ishemic-induced brain damage : A mechanistic study. In: FASEB Journal. 2005 ; Vol. 18, No. 10. pp. 1114-1116.
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Clarkson, A, Liu, H, Pearson, L, Kapoor, M, Harrison, JC, Sammut, IA, Jackson, D & Appleton, I 2005, 'Neuroprotective effects of spermine following hypoxic-ishemic-induced brain damage: A mechanistic study', FASEB Journal, vol. 18, no. 10, pp. 1114-1116. https://doi.org/10.1096/fj.03-1203fje

Neuroprotective effects of spermine following hypoxic-ishemic-induced brain damage : A mechanistic study. / Clarkson, A; Liu, H; Pearson, L; Kapoor, M; Harrison, JC; Sammut, IA; Jackson, David; Appleton, I.

In: FASEB Journal, Vol. 18, No. 10, 2005, p. 1114-1116.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Neuroprotective effects of spermine following hypoxic-ishemic-induced brain damage

T2 - A mechanistic study

AU - Clarkson, A

AU - Liu, H

AU - Pearson, L

AU - Kapoor, M

AU - Harrison, JC

AU - Sammut, IA

AU - Jackson, David

AU - Appleton, I

N1 - Imported on 12 Apr 2017 - DigiTool details were: Journal title (773t) = The FASEB Journal. ISSNs: 0892-6638;

PY - 2005

Y1 - 2005

N2 - The polyamines (spermine, putrescine, and spermidine) can have neurotoxic or neuroprotective properties in models of neurodegeneration. However, assessment in a model of hypoxia'ischemia (HI) has not been defined. Furthermore, the putative mechanisms of neuroprotection have not been elucidated. Therefore, the present study examined the effects of the polyamines in a rat pup model of HI and determined effects on key enzymes involved in inflammation, namely, nitric oxide synthase (NOS) and arginase. In addition, effects on mitochondrial function were investigated. The polyamines or saline were administered i.p. at 10mg/kg/day for 6 days post-HI. Histological assessment 7 days post-HI revealed that only spermine significantly (P<0.01) reduced infarct size from 46.14 ± 10.4mm3 (HI + saline) to 4.9 ± 2.7 mm3. NOS activity was significantly increased following spermine treatment in the left (ligated) hemisphere compared with nonintervention controls (P<0.01) and HI + saline (P<0.05). In contrast, spermine decreased arginase activity compared with HI + saline but was still significantly elevated in comparison to nonintervention controls (P<0.01). Assessment of mitochondrial function in the HI + saline group, revealed significant and extensive damage to complex-I (P<0.01) and IV (P<0.001) and loss of citrate synthase activity (P<0.05). No effect on complex II-III was observed. Spermine treatment significantly prevented all these effects. This study has therefore confirmed the neuroprotective effects of spermine in vivo. However, for the first time, we have shown that this effect may, in part, be due to increased NOS activity and preservation of mitochondrial function.

AB - The polyamines (spermine, putrescine, and spermidine) can have neurotoxic or neuroprotective properties in models of neurodegeneration. However, assessment in a model of hypoxia'ischemia (HI) has not been defined. Furthermore, the putative mechanisms of neuroprotection have not been elucidated. Therefore, the present study examined the effects of the polyamines in a rat pup model of HI and determined effects on key enzymes involved in inflammation, namely, nitric oxide synthase (NOS) and arginase. In addition, effects on mitochondrial function were investigated. The polyamines or saline were administered i.p. at 10mg/kg/day for 6 days post-HI. Histological assessment 7 days post-HI revealed that only spermine significantly (P<0.01) reduced infarct size from 46.14 ± 10.4mm3 (HI + saline) to 4.9 ± 2.7 mm3. NOS activity was significantly increased following spermine treatment in the left (ligated) hemisphere compared with nonintervention controls (P<0.01) and HI + saline (P<0.05). In contrast, spermine decreased arginase activity compared with HI + saline but was still significantly elevated in comparison to nonintervention controls (P<0.01). Assessment of mitochondrial function in the HI + saline group, revealed significant and extensive damage to complex-I (P<0.01) and IV (P<0.001) and loss of citrate synthase activity (P<0.05). No effect on complex II-III was observed. Spermine treatment significantly prevented all these effects. This study has therefore confirmed the neuroprotective effects of spermine in vivo. However, for the first time, we have shown that this effect may, in part, be due to increased NOS activity and preservation of mitochondrial function.

U2 - 10.1096/fj.03-1203fje

DO - 10.1096/fj.03-1203fje

M3 - Article

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SP - 1114

EP - 1116

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 10

ER -