Abstract 15769: Alpha1A-Adrenergic Receptors in Neuroprotection
Background: Alpha-1A-adrenergic receptors (α1A-ARs) have a protective trophic role in the heart. α1A-AR levels are high in the brain, and neuroprotection by norepinephrine is known. Recently, α1A-ARs have been studied for their role in neurogenesis however, direct neuroprotection by α1-AR subtypes is unclear.
Hypothesis: During ischemia or trauma α1A-ARs on neurons mediate neuroprotection, analogous to cardioprotection.
Methods: ex vivo, we quantified ATP levels (marker for survival) in mouse brain slices injured by 10μ M H2O2 and treated for 2h with A61603 (a1A-AR specific agonist) or Vehicle. We quantified the number of dead neurons (propidium iodide (PI) positive) out of total (NeuN positive) in the same treated slices by immunohistochemistry (IHC). In vivo, we measured brain infarct size (BrdU-positive glial cells) after transient focal ischemia and reperfusion (IR) in α1ABKO and WT mice. Also, we measured by anti-mouse IgG IHC the levels of endogenous IgG extravasation (brain blood barrier (BBB) damage) after controlled cortical impact (CCI) in α1ABKO and WT mice.
Results: In vivo, (Fig.1) infarct size in α1ABKOs (N=3) was 2.1 times larger than in WT (N=2). Further, (Fig.2) endogenous IgG intensity (BBB damage) was also 2 fold increased in α1ABKOs (N=2) compared with WT (N=2). Ex vivo, treatment with the α1A agonist A61603 preserved ATP levels after H2O2 (8±1 vs. 5.5±0.5 nmol/mg protein, N=2). A61603 also reduced the number of dead neurons caused by H2O2 (46±0.3 vs. 86±5.3, N=2).
Conclusion: α1-ARs are required for brain protection in vivo during ischemic or traumatic injury, and the α1A-AR subtype mediates neuron protection ex vivo from oxidative stress induced injury.
- © 2011 by American Heart Association, Inc.