J Korean Neurosurg Soc.  2013 Mar;53(3):139-144. 10.3340/jkns.2013.53.3.139.

Isoflurane Induces Transient Anterograde Amnesia through Suppression of Brain-Derived Neurotrophic Factor in Hippocampus

• Cho HJ
• Sung YH
• Lee SH
• Chung JY
• Kang JM
• Yi JW

• KMID: 2190737
• DOI: http://doi.org/10.3340/jkns.2013.53.3.139

Abstract

OBJECTIVE
Transient anterograde amnesia is occasionally observed in a number of conditions, including migraine, focal ischemia, venous flow abnormalities, and after general anesthesia. The inhalation anesthetic, isoflurane, is known to induce transient anterograde amnesia. We examined the involvement of brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) in the underlying mechanisms of the isoflurane-induced transient anterograde amnesia.
METHODS
Adult male Sprague-Dawley rats were divided into three groups : the control group, the 10 minutes after recovery from isoflurane anesthesia group, and the 2 hours after recovery from isoflurane anesthesia group (n=8 in each group). The rats in the isoflurane-exposed groups were anesthetized with 1.2% isoflurane in 75% nitrous oxide and 25% oxygen for 2 hours in a Plexiglas anesthetizing chamber. Short-term memory was determined using the step-down avoidance task. BDNF and TrkB expressions in the hippocampus were evaluated by immunofluorescence staining and western blot analysis.
RESULTS
Latency in the step-down avoidance task was decreased 10 minutes after recovery from isoflurane anesthesia, whereas it recovered to the control level 2 hours after isoflurane anesthesia. The expressions of BDNF and TrkB in the hippocampus were decreased immediately after isoflurane anesthesia but were increased 2 hours after isoflurane anesthesia.
CONCLUSION
In this study, isoflurane anesthesia induced transient anterograde amnesia, and the expressions of BDNF and TrkB in the hippocampus might be involved in the underlying mechanisms of this transient anterograde amnesia.

Keyword

Isoflurane; Anterograde amnesia; Brain-derived neurotrophic factor; Tyrosine kinase B receptor; Hippocampus

MeSH Terms

Adult
Amnesia, Anterograde
Anesthesia
Anesthesia, General
Animals
Blotting, Western
Brain-Derived Neurotrophic Factor
Fluorescent Antibody Technique
Hippocampus
Humans
Inhalation
Ischemia
Isoflurane
Male
Memory, Short-Term
Migraine Disorders
Nitrous Oxide
Oxygen
Polymethyl Methacrylate
Protein-Tyrosine Kinases
Rats
Rats, Sprague-Dawley
Brain-Derived Neurotrophic Factor
Isoflurane
Nitrous Oxide
Oxygen
Polymethyl Methacrylate
Protein-Tyrosine Kinases

Figure

• 

  Fig. 1 Latency in the step-down avoidance task. Latency was expressed as the interval of time in which rats stepped down and placed all four paws on the grid. Any latency >300 seconds was counted as 300 seconds. Results are presented as the mean±standard error of the mean. CON : control group, 10 min : 10 minutes after recovery from isoflurane anesthesia group, 2 h : 2 hours after recovery from isoflurane anesthesia group. *p<0.05 compared to the control group, †p<0.05 compared to the 10 minutes after recovery from isoflurane anesthesia group.

• 

  Fig. 2 Expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. A : Levels of BDNF expression in the hippocampus as shown by western blot and quantitative analyses. B : Photomicrographs showing the neuronal nuclei (NeuN) and BDNF-specific double immunofluorescence staining in CA3 region of the hippocampus. The scale bar represents 100 µm. BDNF expression in the hippocampus of the control group was set as 1.00. The results are presented as the mean±standard error of the mean. CON : control group, 10 min : 10 minutes after recovery from isoflurane anesthesia group, 2 h : 2 hours after recovery from isoflurane anesthesia group, *p<0.05 compared to the control group, †p<0.05 compared to the 10 minutes after recovery from isoflurane anesthesia group.

• 

  Fig. 3 Expression of tyrosine kinase B (TrkB) in the hippocampus. A : Levels of TrkB expression in the hippocampus as shown by western blot and quantitative analyses. B : Photomicrographs showing the neuronal nuclei (NeuN) and TrkB-specific double immunofluorescence staining in CA3 region of the hippocampus. The scale bar represents 50 µm. Levels of TrkB expression in the hippocampus in the control group were set as 1.00. The results are presented as the mean±standard error of the mean. CON : control group, 10 min : 10 minutes after recovery from isoflurane anesthesia group, 2 h : 2 hours after recovery from isoflurane anesthesia group. *p<0.05 compared to the control group, †p<0.05 compared to the 10 minutes after recovery from isoflurane anesthesia group.

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