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Neuroprotective Strategies for Traumatic Brain Injury: Improving Clinical Translation
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Int. J. Mol. Sci. 2014, 15(1), 1402-1417; doi:10.3390/ijms15011402

Phenoxybenzamine Is Neuroprotective in a Rat Model of Severe Traumatic Brain Injury

Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USA
Author to whom correspondence should be addressed.
Received: 25 November 2013 / Revised: 1 January 2014 / Accepted: 14 January 2014 / Published: 20 January 2014
(This article belongs to the Special Issue Neuroprotective Strategies 2014)
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Phenoxybenzamine (PBZ) is an FDA approved α-1 adrenergic receptor antagonist that is currently used to treat symptoms of pheochromocytoma. However, it has not been studied as a neuroprotective agent for traumatic brain injury (TBI). While screening neuroprotective candidates, we found that phenoxybenzamine reduced neuronal death in rat hippocampal slice cultures following exposure to oxygen glucose deprivation (OGD). Using this system, we found that phenoxybenzamine reduced neuronal death over a broad dose range (0.1 µM–1 mM) and provided efficacy when delivered up to 16 h post-OGD. We further tested phenoxybenzamine in the rat lateral fluid percussion model of TBI. When administered 8 h after TBI, phenoxybenzamine improved neurological severity scoring and foot fault assessments. At 25 days post injury, phenoxybenzamine treated TBI animals also showed a significant improvement in both learning and memory compared to saline treated controls. We further examined gene expression changes within the cortex following TBI. At 32 h post-TBI phenoxybenzamine treated animals had significantly lower expression of pro-inflammatory signaling proteins CCL2, IL1β, and MyD88, suggesting that phenoxybenzamine may exert a neuroprotective effect by reducing neuroinflammation after TBI. These data suggest that phenonxybenzamine may have application in the treatment of TBI. View Full-Text
Keywords: phenoxybenzamine; traumatic brain injury; neuroprotection; morris water maze phenoxybenzamine; traumatic brain injury; neuroprotection; morris water maze

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Rau, T.F.; Kothiwal, A.; Rova, A.; Rhoderick, J.F.; Poulsen, D.J. Phenoxybenzamine Is Neuroprotective in a Rat Model of Severe Traumatic Brain Injury. Int. J. Mol. Sci. 2014, 15, 1402-1417.

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