Abstract 19: Neurophysiological Responses Of Recovery In Pediatric Mice Compared To Adult Mice With Transient Focal Cerebral Ischemia
Introduction: Ischemic stroke is the fourth leading cause of death in the United States and is increasingly being recognized as a disease that occurs in people of all ages, not just the elderly. Studies suggest that the immature developing brain may have a greater degree of plasticity compared to the adult, thereby enhancing functional recovery to a greater extent during development.
Hypothesis: Pediatric mice exhibit greater recovery from hippocampal synaptic function following experimental stroke than adults.
Methods: Extracellular field recordings of CA1 neurons were performed in acute hippocampal slices prepared at 24 hrs, 7 or 30 days after recovery from middle cerebral artery occlusion (MCAO) and compared to sham control mice.
Results: In adult mice, hippocampal long-term potentiation (LTP) is impaired as early as 24 hrs after experimental stroke and remains impaired for at least 30 days in both the ipsilateral and contralateral, non-injured hemisphere. However, in pediatric mice, LTP is impaired as early as 24 hrs after MCAO and remained impaired in the ipsilateral side 7 days after MCAO, but recovered in the contralateral side at 7 days after MCAO. At day 30 post-stroke, pediatric mice display a full recovery of synaptic function in both hemispheres. Furthermore, significant experimental data is emerging demonstrating an imbalance between inhibitory and excitatory cortical pathways after ischemic stroke, suggesting that reducing GABAergic inhibitory transmission enhances recovery. To test this, hippocampal slices were incubated in L655,708 (100nM), an inverse agonist selective for α5 subunit-containing GABAA receptors. Our data shows that synaptic plasticity was rescued in both pediatric and adult mice in the presence of L655,708 at all-time points tested.
Conclusion: The present study demonstrates that transient focal ischemia causes functional impairment in the hippocampus at various time points after MCAO and that recovery of synaptic function is more robust in the young brain. In addition, we observed that excessive GABA activity may contribute to impaired synaptic function following ischemic injury, thus inhibition of specific GABA activity may provide a new therapeutic approach to improve functional recovery after stroke.
Author Disclosures: J.E. Orfila: None. H. Grewal: None. T.J. Bernard: None. W.B. Macklin: None. R.J. Traystman: None. P.S. Herson: None.
This research has received full or partial funding support from the American Heart Association, National Center.
- © 2015 by American Heart Association, Inc.