Nimodipine prevents transient cognitive dysfunction after moderate hypoxia in adult mice

Michael Haile, Fred Limson, Kevin Gingrich, Yong Sheng Li, David Quartermain, Thomas Blanck, Alex Bekker

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Cognitive changes associated with moderate hypoxia may be related to the elevation of cytosolic calcium (Ca 2+) levels which may, in turn, affect neurotransmitter synthesis and metabolism. We tested whether treatment with nimodipine (NIMO), an L-type Ca 2+ channel blocker, would preserve working memory after hypoxic hypoxia. Methods: We randomized 157 Swiss-Webster, 30 to 35 g mice (6 to 8 wk) to 6 groups, which were exposed to the following gas mixtures for 1 hour: (1) 0 2 21%; (2) 0 2 21% followed by 0.1 mg/kg of subcutaneous NIMO; (3) 0 2 21% followed by vehicle (60% polyethylene glycol/40% methanol); (4) 0 2 10%; (5) 0 2 10% then NIMO; (6) 0 2 10% then vehicle. The Object Recognition Test (ORT) was given once either on Day 1 or Day 7 to assess changes in short-term memory. ORT exploits the tendency of mice to prefer novel over familiar objects. Two identical objects were placed in an arena for 15 minutes of training. During the testing 1 hour later, one of the objects was replaced by a new object. Recognition Index (RI) was used to compare performance. It is defined as the time spent exploring the novel object divided by the time spent exploring both objects, the novel plus the familiar, and this ratio is converted to a percentage. RI was analyzed with analysis of variance. Tukey Honestly Significant Difference tests were used for post hoc comparisons when appropriate. P values & lt; 0.05 were considered significant. Results: RI for the control group was 68.3% (SE & plusmn; 3.6%). RI was 53.7% (SE & plusmn; 3.8%) for the 10% 0 2 group on the first posttreatment day. 0 2 saturation (Sp0 2) for the hypoxic group was 71.7% (SE & plusmn; 0.5%). By Day 7, RI for the 10% 0 2 group increased to 64.2% (SE & plusmn; 4.7%), which was not significantly different from control. On Day 1, RI was 68.6% (SE & plusmn; 5.2%) for hypoxic rodents treated with NIMO. These results were statistically significant. Low RI indicates impaired working memory and high RI indicates intact working memory. These results suggest that NIMO prevented impairment of working memory after moderate hypoxia. Conclusions: NIMO reverses the disturbance of short-term working memory caused by moderate hypoxia in mice. The results may have implications for cognitive changes linked to Ca 2+ homeostasis in the postoperative period. & copy; 2009 by Lippincott Williams & amp; Wilkins.

Original languageEnglish (US)
Pages (from-to)140-144
Number of pages5
JournalJournal of Neurosurgical Anesthesiology
Volume21
Issue number2
DOIs
StatePublished - Apr 2009

Fingerprint

Nimodipine
Short-Term Memory
Hypoxia
Recognition (Psychology)
Cognitive Dysfunction
Postoperative Period
Neurotransmitter Agents
Methanol
Rodentia
Analysis of Variance
Homeostasis
Gases
Calcium

Keywords

  • Calcium influx
  • Cognitive dysfunction
  • Moderate hypoxia
  • Nimodipine
  • Object recognition
  • Short-term memory
  • Working memory

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Clinical Neurology
  • Surgery

Cite this

Nimodipine prevents transient cognitive dysfunction after moderate hypoxia in adult mice. / Haile, Michael; Limson, Fred; Gingrich, Kevin; Li, Yong Sheng; Quartermain, David; Blanck, Thomas; Bekker, Alex.

In: Journal of Neurosurgical Anesthesiology, Vol. 21, No. 2, 04.2009, p. 140-144.

Research output: Contribution to journalArticle

Haile, Michael ; Limson, Fred ; Gingrich, Kevin ; Li, Yong Sheng ; Quartermain, David ; Blanck, Thomas ; Bekker, Alex. / Nimodipine prevents transient cognitive dysfunction after moderate hypoxia in adult mice. In: Journal of Neurosurgical Anesthesiology. 2009 ; Vol. 21, No. 2. pp. 140-144.
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AU - Limson, Fred

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N2 - Cognitive changes associated with moderate hypoxia may be related to the elevation of cytosolic calcium (Ca 2+) levels which may, in turn, affect neurotransmitter synthesis and metabolism. We tested whether treatment with nimodipine (NIMO), an L-type Ca 2+ channel blocker, would preserve working memory after hypoxic hypoxia. Methods: We randomized 157 Swiss-Webster, 30 to 35 g mice (6 to 8 wk) to 6 groups, which were exposed to the following gas mixtures for 1 hour: (1) 0 2 21%; (2) 0 2 21% followed by 0.1 mg/kg of subcutaneous NIMO; (3) 0 2 21% followed by vehicle (60% polyethylene glycol/40% methanol); (4) 0 2 10%; (5) 0 2 10% then NIMO; (6) 0 2 10% then vehicle. The Object Recognition Test (ORT) was given once either on Day 1 or Day 7 to assess changes in short-term memory. ORT exploits the tendency of mice to prefer novel over familiar objects. Two identical objects were placed in an arena for 15 minutes of training. During the testing 1 hour later, one of the objects was replaced by a new object. Recognition Index (RI) was used to compare performance. It is defined as the time spent exploring the novel object divided by the time spent exploring both objects, the novel plus the familiar, and this ratio is converted to a percentage. RI was analyzed with analysis of variance. Tukey Honestly Significant Difference tests were used for post hoc comparisons when appropriate. P values & lt; 0.05 were considered significant. Results: RI for the control group was 68.3% (SE & plusmn; 3.6%). RI was 53.7% (SE & plusmn; 3.8%) for the 10% 0 2 group on the first posttreatment day. 0 2 saturation (Sp0 2) for the hypoxic group was 71.7% (SE & plusmn; 0.5%). By Day 7, RI for the 10% 0 2 group increased to 64.2% (SE & plusmn; 4.7%), which was not significantly different from control. On Day 1, RI was 68.6% (SE & plusmn; 5.2%) for hypoxic rodents treated with NIMO. These results were statistically significant. Low RI indicates impaired working memory and high RI indicates intact working memory. These results suggest that NIMO prevented impairment of working memory after moderate hypoxia. Conclusions: NIMO reverses the disturbance of short-term working memory caused by moderate hypoxia in mice. The results may have implications for cognitive changes linked to Ca 2+ homeostasis in the postoperative period. & copy; 2009 by Lippincott Williams & amp; Wilkins.

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KW - Calcium influx

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KW - Object recognition

KW - Short-term memory

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