1. Austin Peters, MD, CA-3 Oregon Health & Science University
Ketamine Alters Hippocampal Cell Proliferation after Traumatic Brain Injury and Improves Learning in Mice
Talk briefly about self and research time/track.
Austin Peters, MD, CA-3
Oregon Health & Science University

2. Background/Design BACKGROUND
After injury, there is widespread cell loss and dysfunction in the brain.
Some limited regeneration occurs.
Post-injury, neurogenesis increases.
Potentially helpful vs. harmful if newly developed cells are dysfunctional.
Neurogenesis is modulated by receptors directly affected by anesthetic drugs, including the NMDA-receptor antagonist ketamine.
Given ketamine is increasingly being used in TBI, we wanted to see if clinically relevant concentrations of ketamine would affect the brain’s response to injury
DESIGN
Adult mice randomized to controlled cortical impact or sham, receive 7-day drug pump of ketamine (30mg/kg/day) or vehicle.
Immunohistochemistry at 3 days, 2 weeks and 6 weeks post-intervention and behavioral testing at 4 weeks post-intervention.
Bonaguidi et. al. 2011

3. Ketamine Increases Hippocampal Cell Proliferation After CCI

4. Post-Injury Ketamine Inhibits Neurogenesis 2 Weeks After CCI
Significantly fewer neurons born after injury when exposed to ketamine. Looking at all cells (not only injury-related), ketamine groups had fewer adult-born neurons.

5. Ketamine Induces Rapid Microgliogenesis & Inhibits Astrogliogenesis After CCI
Explain astrocyte function: Astroglia are supportive, non-neuronal cells in the brain (release growth factors, absorb excitatory molecules).

6. Ketamine Ameliorates the CCI-Induced Impairment in Water Maze Reversal Learning
Learning outcomes are improved with ketamine. Remove D.

7. Thank You OHSU Department of Anesthesiology & Perioperative Medicine
Dr. Jeffrey Kirsch, Chair
Dr. Christopher Swide, Program Director
Dr. Jeff Iliff, Vice Chair of Research
VA Portland HCS
Vollum Institute
Dr. Eric Schnell
Dr. Laura Villasana
Dr. Gary Westbrook
Schnell/Westbrook Labmates
Dr. Christina Chatzi
Will Hendricks
Kathleen Beeson
Jaimie Adelson
Brian Jones
Chris Vaaga
Financial Support
FAER RFG (AP)
VHA CDA-2 award S (ES)
VHA Merit Award I01-BX (ES)
OCTRI HIP Grant TL1TR000129
NINDS P30 grant (P30 NS061800; Aicher, PI)