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Simvastatin treatment duration and cognitive preservation in experimental subarachnoid hemorrhage.

Publication ,  Journal Article
Takata, K; Sheng, H; Borel, CO; Laskowitz, DT; Warner, DS; Lombard, FW
Published in: J Neurosurg Anesthesiol
October 2009

Cognitive dysfunction, a significant complication after subarachnoid hemorrhage (SAH), affects up to 60% of survivors. We hypothesized that oral simvastatin would improve vestibulomotor function and reduce cognitive dysfunction after experimental SAH in the rat, and explored the effects of simvastatin on vasospasm and regional cerebral blood flow (rCBF). In total 160 rats were enrolled. Randomization to simvastatin or vehicle occurred after double intracisternal blood injections. Effects of simvastatin 10 mg/kg/d (SV10), simvastatin 1.5 mg/kg/d, or vehicle on rotarod, Morris water maze, neuronal survival, cerebral arterial diameter, and rCBF were determined by a blinded observer (n=15/group). A dose dependent response to simvastatin was observed, with more rapid improvement in vestibulomotor function, less basilar arterial vasospasm, and improved cortical neuronal survival with SV10. However, rotarod performance in the SV10 group deteriorated after 1 week, which correlated with the increased plasma creatine kinase levels (r=-0.737; P=0.0002). Furthermore, when simvastatin was discontinued after 2 weeks, the usual treatment duration in SAH clinical trials, rotarod performance deteriorated acutely, rCBF returned to control values, and no long-term benefit was observed in terms of visual spatial memory. Continuing simvastatin 1.5 mg/kg/d for 5 weeks resulted in sustained improvement in rotarod performance, reduced escape latency (P=0.001), swimming distance (P=0.002), and swimming speed (P=0.03) versus vehicle (n=12/group). Our results indicate that long-term cognitive dysfunction after experimental SAH in the rat can be reduced by simvastatin. However, treatment had to be extended beyond 2 weeks, the traditional risk period for angiographic vasospasm, to improve long-term outcome.

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Published In

J Neurosurg Anesthesiol

DOI

EISSN

1537-1921

Publication Date

October 2009

Volume

21

Issue

4

Start / End Page

326 / 333

Location

United States

Related Subject Headings

  • Subarachnoid Hemorrhage
  • Simvastatin
  • Rats, Wistar
  • Rats
  • Postural Balance
  • Neurons
  • Maze Learning
  • Male
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Creatine Kinase
 

Citation

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Takata, K., Sheng, H., Borel, C. O., Laskowitz, D. T., Warner, D. S., & Lombard, F. W. (2009). Simvastatin treatment duration and cognitive preservation in experimental subarachnoid hemorrhage. J Neurosurg Anesthesiol, 21(4), 326–333. https://doi.org/10.1097/ANA.0b013e3181acfde7
Takata, Ken, Huaxin Sheng, Cecil O. Borel, Daniel T. Laskowitz, David S. Warner, and Frederick W. Lombard. “Simvastatin treatment duration and cognitive preservation in experimental subarachnoid hemorrhage.J Neurosurg Anesthesiol 21, no. 4 (October 2009): 326–33. https://doi.org/10.1097/ANA.0b013e3181acfde7.
Takata K, Sheng H, Borel CO, Laskowitz DT, Warner DS, Lombard FW. Simvastatin treatment duration and cognitive preservation in experimental subarachnoid hemorrhage. J Neurosurg Anesthesiol. 2009 Oct;21(4):326–33.
Takata, Ken, et al. “Simvastatin treatment duration and cognitive preservation in experimental subarachnoid hemorrhage.J Neurosurg Anesthesiol, vol. 21, no. 4, Oct. 2009, pp. 326–33. Pubmed, doi:10.1097/ANA.0b013e3181acfde7.
Takata K, Sheng H, Borel CO, Laskowitz DT, Warner DS, Lombard FW. Simvastatin treatment duration and cognitive preservation in experimental subarachnoid hemorrhage. J Neurosurg Anesthesiol. 2009 Oct;21(4):326–333.

Published In

J Neurosurg Anesthesiol

DOI

EISSN

1537-1921

Publication Date

October 2009

Volume

21

Issue

4

Start / End Page

326 / 333

Location

United States

Related Subject Headings

  • Subarachnoid Hemorrhage
  • Simvastatin
  • Rats, Wistar
  • Rats
  • Postural Balance
  • Neurons
  • Maze Learning
  • Male
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Creatine Kinase