Stroke is the leading cause of adult disability. Stroke is produced both by direct blockade of blood flow and by hemorrhage. Intracerebral hemorrhage is the second leading cause of stroke. Intracerebral hemorrhage (ICH) has even less proportionate recovery than non-hemorrhagic stroke. However, in ICH there is a limited process of initial recovery and regaining of lost brain function. The mechanisms of functional recovery in ICH have not been studied. This application will determine the mechanisms for the formation of new connections and recovery in the brain after ICH. In non-hemorrhagic stroke, new connections are formed in the first month after the stroke, a process termed post-stroke axonal sprouting. The PI on this application proposal and other labs have identified the molecular mechanisms for axonal sprouting after stroke, and the association of axonal sprouting with functional recovery. The proposed studies will use newly developed techniques to identify the new patterns of connections that form in the motor system after ICH, the gene systems that mediate this axonal sprouting, and the causal link between axonal sprouting and functional recovery mediated through these gene systems, so as to determine molecules that may serve as therapeutic targets for neural repair in this disease.

Public Health Relevance

Intracerebral hemorrhage is the second leading cause of stroke in the United States, and the most severe cause of stroke-related disability. There have been no studies on the mechanisms of re-connection and repair in the brain after intracerebral hemorrhage. The studies in this application will determine how the brain reconnects after stroke, the molecules that mediate this reconnection, and begin to identify potential new repair therapies for this disease.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Study Section
Acute Neural Injury and Epilepsy Study Section (ANIE)
Program Officer
Koenig, James I
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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Bosetti, Francesca; Koenig, James I; Ayata, Cenk et al. (2017) Translational Stroke Research: Vision and Opportunities. Stroke 48:2632-2637
Carmichael, S Thomas; Kathirvelu, Balachandar; Schweppe, Catherine A et al. (2017) Molecular, cellular and functional events in axonal sprouting after stroke. Exp Neurol 287:384-394
Carmichael, S Thomas (2016) Emergent properties of neural repair: elemental biology to therapeutic concepts. Ann Neurol 79:895-906
Carmichael, S Thomas (2016) The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative. Neurotherapeutics 13:348-59
Dobkin, Bruce H; Carmichael, S Thomas (2016) The Specific Requirements of Neural Repair Trials for Stroke. Neurorehabil Neural Repair 30:470-8
Kathirvelu, Balachandar; Carmichael, S Thomas (2015) Intracerebral hemorrhage in mouse models: therapeutic interventions and functional recovery. Metab Brain Dis 30:449-59
Overman, Justine J; Carmichael, S Thomas (2014) Plasticity in the injured brain: more than molecules matter. Neuroscientist 20:15-28
Barratt, Harriet E; Lanman, Tyler A; Carmichael, S Thomas (2014) Mouse intracerebral hemorrhage models produce different degrees of initial and delayed damage, axonal sprouting, and recovery. J Cereb Blood Flow Metab 34:1463-71