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Atorvastatin ameliorates cerebral vasospasm and early brain injury after subarachnoid hemorrhage and inhibits caspase-dependent apoptosis pathway.

Cheng G, Wei L, Zhi-Dan S, Shi-Guang Z, Xiang-Zhen L - BMC Neurosci (2009)

Bottom Line: Hydroxymethylglutaryl coenzyme A reductase inhibitors, also known as statins, has the neuroprotective effects and ameliorating CVS after SAH.TUNEL-positive cells were reduced markedly both in basilar artery and in brain cortex by atorvastatin.The neuroprotective effects of atorvastatin after SAH may be related to its inhibition of caspase-dependent proapoptotic pathway based on the present results.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, Heilongjiang, PR China. doctorgaocheng@yahoo.com.cn

ABSTRACT

Background: Cerebral vasospasm (CVS) and early brain injury remain major causes of morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). Hydroxymethylglutaryl coenzyme A reductase inhibitors, also known as statins, has the neuroprotective effects and ameliorating CVS after SAH. This study was designed to explore apoptosis inhibiting effects of atorvastatin and its potential apoptotic signal pathway after SAH.

Results: Preserving blood-brain-barrier permeability, decreasing brain edema, increasing neurological scores and ameliorating cerebral vasospasm were obtained after prophylactic use of atorvastatin. TUNEL-positive cells were reduced markedly both in basilar artery and in brain cortex by atorvastatin. Apoptosis-related proteins P53, AIF and Cytochrome C were up-regulated after SAH, while they were not affected by atorvastatin. In addition, up-regulation of caspase-3 and caspase-8 after SAH was decreased by atorvastatin treatment both in mRNA and in protein levels.

Conclusion: The neuroprotective effects of atorvastatin after SAH may be related to its inhibition of caspase-dependent proapoptotic pathway based on the present results.

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TUNEL staining of basilar artery and basal cortex after SAH. Few apoptosis cells were observed in sham operated control rats (A and F). Increased TUNEL positive staining was observed in SAH+DMSO (B and G) and SAH rats (D and I), which was reduced markedly by atorvastatin. (C and H). Scale bar represents 200 μm. Quantitive analysis showed an obvious reduction in number of apoptosis cells (number/mm2) by atorvastatin compared with that in the DMSO group. (E and J, P < 0.01 vs DMSO group).
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Figure 1: TUNEL staining of basilar artery and basal cortex after SAH. Few apoptosis cells were observed in sham operated control rats (A and F). Increased TUNEL positive staining was observed in SAH+DMSO (B and G) and SAH rats (D and I), which was reduced markedly by atorvastatin. (C and H). Scale bar represents 200 μm. Quantitive analysis showed an obvious reduction in number of apoptosis cells (number/mm2) by atorvastatin compared with that in the DMSO group. (E and J, P < 0.01 vs DMSO group).

Mentions: Few TUNEL positive cells were detected in sham operated animals. At 24 hour after SAH, TUNEL positive cells appeared both in basilar artery and in basal cortex in SAH rats. Treatment with atorvastatin produced remarkable reduction of TUNEL positive staining both in basilar artery and in brain cortex (Figure 1A–J).


Atorvastatin ameliorates cerebral vasospasm and early brain injury after subarachnoid hemorrhage and inhibits caspase-dependent apoptosis pathway.

Cheng G, Wei L, Zhi-Dan S, Shi-Guang Z, Xiang-Zhen L - BMC Neurosci (2009)

TUNEL staining of basilar artery and basal cortex after SAH. Few apoptosis cells were observed in sham operated control rats (A and F). Increased TUNEL positive staining was observed in SAH+DMSO (B and G) and SAH rats (D and I), which was reduced markedly by atorvastatin. (C and H). Scale bar represents 200 μm. Quantitive analysis showed an obvious reduction in number of apoptosis cells (number/mm2) by atorvastatin compared with that in the DMSO group. (E and J, P < 0.01 vs DMSO group).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651177&req=5

Figure 1: TUNEL staining of basilar artery and basal cortex after SAH. Few apoptosis cells were observed in sham operated control rats (A and F). Increased TUNEL positive staining was observed in SAH+DMSO (B and G) and SAH rats (D and I), which was reduced markedly by atorvastatin. (C and H). Scale bar represents 200 μm. Quantitive analysis showed an obvious reduction in number of apoptosis cells (number/mm2) by atorvastatin compared with that in the DMSO group. (E and J, P < 0.01 vs DMSO group).
Mentions: Few TUNEL positive cells were detected in sham operated animals. At 24 hour after SAH, TUNEL positive cells appeared both in basilar artery and in basal cortex in SAH rats. Treatment with atorvastatin produced remarkable reduction of TUNEL positive staining both in basilar artery and in brain cortex (Figure 1A–J).

Bottom Line: Hydroxymethylglutaryl coenzyme A reductase inhibitors, also known as statins, has the neuroprotective effects and ameliorating CVS after SAH.TUNEL-positive cells were reduced markedly both in basilar artery and in brain cortex by atorvastatin.The neuroprotective effects of atorvastatin after SAH may be related to its inhibition of caspase-dependent proapoptotic pathway based on the present results.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, Heilongjiang, PR China. doctorgaocheng@yahoo.com.cn

ABSTRACT

Background: Cerebral vasospasm (CVS) and early brain injury remain major causes of morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). Hydroxymethylglutaryl coenzyme A reductase inhibitors, also known as statins, has the neuroprotective effects and ameliorating CVS after SAH. This study was designed to explore apoptosis inhibiting effects of atorvastatin and its potential apoptotic signal pathway after SAH.

Results: Preserving blood-brain-barrier permeability, decreasing brain edema, increasing neurological scores and ameliorating cerebral vasospasm were obtained after prophylactic use of atorvastatin. TUNEL-positive cells were reduced markedly both in basilar artery and in brain cortex by atorvastatin. Apoptosis-related proteins P53, AIF and Cytochrome C were up-regulated after SAH, while they were not affected by atorvastatin. In addition, up-regulation of caspase-3 and caspase-8 after SAH was decreased by atorvastatin treatment both in mRNA and in protein levels.

Conclusion: The neuroprotective effects of atorvastatin after SAH may be related to its inhibition of caspase-dependent proapoptotic pathway based on the present results.

Show MeSH
Related in: MedlinePlus