Effects of fetal exposure to isoflurane on postnatal memory and learning in rats

Huafeng Wei, MD, PhDAssistant ProfessorDepartment of Anesthesiology and Critical CareUniversity of Pennsylvania

Financial Disclosure

Grant Support:Grant Support:

March of Dimes Birth Defect Foundation March of Dimes Birth Defect Foundation ( #12-FY05-62)( #12-FY05-62)

NIH NIGMS K08 073224-02NIH NIGMS K08 073224-02

Department of Anesthesiology andDepartment of Anesthesiology andCritical Care at University of PennsylvaniaCritical Care at University of PennsylvaniaE+D fundE+D fund

Is Isoflurane Neurotoxic to Fetus Developing Brain?

Isoflurane induced apoptosis dose-and time-Isoflurane induced apoptosis dose-and time-dependently in different neuronal cultures. dependently in different neuronal cultures.

Isoflurane induced apoptosis in the Isoflurane induced apoptosis in the developing brains of 7-day-old rat pups and developing brains of 7-day-old rat pups and subsequent memory and learning disability. subsequent memory and learning disability.

Isoflurane caused permanent memory loss, Isoflurane caused permanent memory loss, learning disability in aged rats.learning disability in aged rats.

Hypothesis: Isoflurane inhaled to pregnant Hypothesis: Isoflurane inhaled to pregnant mothers induced apoptosis in fetus mothers induced apoptosis in fetus developing brain and postnatal memory and developing brain and postnatal memory and learning disability.learning disability.

1.3% Isoflurane Inhibited Apoptosis in Fetus Hippocampus CA1 and Retrosplenial Cortex

Caspase-3 Density

Hippocampus CA1

2h 18h P50

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350 Control1.3% Iso***

Hippocampus CA1

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2h 18h P50

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Retrosplenial Cortex

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Retrosplenial Cortex

Isoflurane Improved Spatial Reference Memory In Juvenile But

Not Adult Rats

Probe Test, * Means P<0.05

P36 P1190

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Summary 1.3% isoflurane for 6 hour in pregnant rats 1.3% isoflurane for 6 hour in pregnant rats

inhibited spontaneous apoptosis in fetus inhibited spontaneous apoptosis in fetus brain at 2 hour, but not at 18 hour or brain at 2 hour, but not at 18 hour or postnatal day 5 after treatment.postnatal day 5 after treatment.

1.3% isoflurane for 6 hour in pregnant rats 1.3% isoflurane for 6 hour in pregnant rats improved spatial reference memory in improved spatial reference memory in postnatal juvenile rats (P36), but not in postnatal juvenile rats (P36), but not in adult rats (P119). adult rats (P119).

1.3% isoflurane for 6 hour in pregnant rats 1.3% isoflurane for 6 hour in pregnant rats did not affect learning in postnatal rats.did not affect learning in postnatal rats.

Acknowledgement

University of PennsylvaniaUniversity of Pennsylvania

Grace Liang, Yujuan Li, Shouping Wang, Qiujun Wang, Wenlin Wei, Baobin Kang, Qing Cheng Meng

Roderic Eckenhoff, Randy Pittman, Roderic Eckenhoff, Randy Pittman, Maryellen EckenhoffMaryellen Eckenhoff

The Morris Water Maze: A sensitive test of rodent memory, learning and behavior.

Cued test (Swimming ability, P28)

Place test (Learning and memory, P32, P115)

Probe test (Memory, P36, P120)