Bone morphogenetic protein-6 reduces ischemia-induced brain damage in rats

Yun Wang, Chen Fu Chang, Marisela Morales, Jenny Chou, Hui Ling Chen, Yung Hsiao Chiang, Shinn Zong Lin, Jean Lud Cadet, Xiaolin Deng, Jia Yi Wang, Su Yu Chen, Paul L. Kaplan, Barry J. Hoffer

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Background and Purpose - Bone morphogenetic protein-6 (BMP6) and its receptors are expressed in adult and fetal brain. Receptors for BMP6 are upregulated in adult brain after injury, leading to the suggestion that BMP6 is involved in the physiological response to neuronal injury. The purpose of this study was to determine whether there was a neuroprotective effect of BMP6 in vivo and in vitro. Methods - Lactate dehydrogenase and microtubule-associated protein-2 (MAP-2) activities were used to determine the protective effect of BMP6 against H2O2 in primary cortical cultures. The neuroprotective effects of BMP6 were also studied in chloral hydrate-anesthetized rats. BMP6 or vehicle was injected into right cerebral cortex before transient right middle cerebral artery (MCA) ligation. Animals were killed for triphenyl-tetrazolium chloride staining, caspase-3 immunoreactivity and enzymatic assays, and TUNEL assay. A subgroup of animals were used for locomotor behavioral assays. Results - Application of H2O2 increased lactate dehydrogenase activity and decreased the density of MAP-2(+) neurons in culture. Both responses were attenuated by BMP6 pretreatment. Complementary in vivo studies showed that pretreatment with BMP6 increased motor performance and generated less cerebral infarction induced by MCA ligation/reperfusion in rats. Pretreatment with BMP6 did not alter cerebral blood flow or physiological parameters. There was decreased ischemia-induced caspase-3 immunoreactivity, caspase-3 enzymatic activity, and density of TUNEL-positive cells in ischemic cortex in BMP6-treated animals. Conclusions - BMP6 reduces ischemia/reperfusion injury, perhaps by attenuating molecular events underlying apoptosis.

Original languageEnglish
Pages (from-to)2170-2178
Number of pages9
JournalStroke
Volume32
Issue number9
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Bone Morphogenetic Protein 6
Brain Ischemia
Caspase 3
Microtubule-Associated Proteins
In Situ Nick-End Labeling
Neuroprotective Agents
L-Lactate Dehydrogenase
Ligation
Cerebrovascular Circulation
Chloral Hydrate
Middle Cerebral Artery Infarction
Middle Cerebral Artery
Enzyme Assays
Reperfusion Injury
Cerebral Cortex

Keywords

  • Apoptosis
  • Bone morphogenetic proteins
  • Cerebral ischemia
  • Neuroprotection
  • Rats

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Wang, Y., Chang, C. F., Morales, M., Chou, J., Chen, H. L., Chiang, Y. H., ... Hoffer, B. J. (2001). Bone morphogenetic protein-6 reduces ischemia-induced brain damage in rats. Stroke, 32(9), 2170-2178.

Bone morphogenetic protein-6 reduces ischemia-induced brain damage in rats. / Wang, Yun; Chang, Chen Fu; Morales, Marisela; Chou, Jenny; Chen, Hui Ling; Chiang, Yung Hsiao; Lin, Shinn Zong; Cadet, Jean Lud; Deng, Xiaolin; Wang, Jia Yi; Chen, Su Yu; Kaplan, Paul L.; Hoffer, Barry J.

In: Stroke, Vol. 32, No. 9, 2001, p. 2170-2178.

Research output: Contribution to journalArticle

Wang, Y, Chang, CF, Morales, M, Chou, J, Chen, HL, Chiang, YH, Lin, SZ, Cadet, JL, Deng, X, Wang, JY, Chen, SY, Kaplan, PL & Hoffer, BJ 2001, 'Bone morphogenetic protein-6 reduces ischemia-induced brain damage in rats', Stroke, vol. 32, no. 9, pp. 2170-2178.
Wang Y, Chang CF, Morales M, Chou J, Chen HL, Chiang YH et al. Bone morphogenetic protein-6 reduces ischemia-induced brain damage in rats. Stroke. 2001;32(9):2170-2178.
Wang, Yun ; Chang, Chen Fu ; Morales, Marisela ; Chou, Jenny ; Chen, Hui Ling ; Chiang, Yung Hsiao ; Lin, Shinn Zong ; Cadet, Jean Lud ; Deng, Xiaolin ; Wang, Jia Yi ; Chen, Su Yu ; Kaplan, Paul L. ; Hoffer, Barry J. / Bone morphogenetic protein-6 reduces ischemia-induced brain damage in rats. In: Stroke. 2001 ; Vol. 32, No. 9. pp. 2170-2178.
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AU - Wang, Yun

AU - Chang, Chen Fu

AU - Morales, Marisela

AU - Chou, Jenny

AU - Chen, Hui Ling

AU - Chiang, Yung Hsiao

AU - Lin, Shinn Zong

AU - Cadet, Jean Lud

AU - Deng, Xiaolin

AU - Wang, Jia Yi

AU - Chen, Su Yu

AU - Kaplan, Paul L.

AU - Hoffer, Barry J.

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N2 - Background and Purpose - Bone morphogenetic protein-6 (BMP6) and its receptors are expressed in adult and fetal brain. Receptors for BMP6 are upregulated in adult brain after injury, leading to the suggestion that BMP6 is involved in the physiological response to neuronal injury. The purpose of this study was to determine whether there was a neuroprotective effect of BMP6 in vivo and in vitro. Methods - Lactate dehydrogenase and microtubule-associated protein-2 (MAP-2) activities were used to determine the protective effect of BMP6 against H2O2 in primary cortical cultures. The neuroprotective effects of BMP6 were also studied in chloral hydrate-anesthetized rats. BMP6 or vehicle was injected into right cerebral cortex before transient right middle cerebral artery (MCA) ligation. Animals were killed for triphenyl-tetrazolium chloride staining, caspase-3 immunoreactivity and enzymatic assays, and TUNEL assay. A subgroup of animals were used for locomotor behavioral assays. Results - Application of H2O2 increased lactate dehydrogenase activity and decreased the density of MAP-2(+) neurons in culture. Both responses were attenuated by BMP6 pretreatment. Complementary in vivo studies showed that pretreatment with BMP6 increased motor performance and generated less cerebral infarction induced by MCA ligation/reperfusion in rats. Pretreatment with BMP6 did not alter cerebral blood flow or physiological parameters. There was decreased ischemia-induced caspase-3 immunoreactivity, caspase-3 enzymatic activity, and density of TUNEL-positive cells in ischemic cortex in BMP6-treated animals. Conclusions - BMP6 reduces ischemia/reperfusion injury, perhaps by attenuating molecular events underlying apoptosis.

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