Matthew J Chiocco

National Institute on Drug Abuse, Maryland, United States

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Publications (3)10.28 Total impact

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    ABSTRACT: Following the onset of an ischemic brain injury, the excitatory neurotransmitter glutamate is released. The excitotoxic effects of glutamate are a major contributor to the pathogenesis of a stroke. The aim of this study was to examine if overexpression of a glutamate transporter (GLT-1) reduces ischemic brain injury in a rat model of stroke. We generated an adeno-associated viral (AAV) vector expressing the rat GLT-1 cDNA (AAV-GLT1). Functional expression of AAV-GLT1 was confirmed by increased glutamate clearance rate in non-stroke rat brain as measured by in vivo amperometry. AAV-GLT1 was injected into future cortical region of infarction 3 weeks prior to 60 min middle cerebral artery occlusion (MCAo). Tissue damage was assessed at one and two days after MCAo using TUNEL and TTC staining, respectively. Behavioral testing was performed at 2, 8 and 14 days post-stroke. Animals receiving AAV-GLT1, compared to AAV-GFP, showed significant decreases in the duration and magnitude of extracellular glutamate, measured by microdialysis, during the 60 minute MCAo. A significant reduction in brain infarction and DNA fragmentation was observed in the region of AAV-GLT1 injection. Animals that received AAV-GLT1 showed significant improvement in behavioral recovery following stroke compared to the AAV-GFP group. We demonstrate that focal overexpression of the glutamate transporter, GLT-1, significantly reduces ischemia-induced glutamate overflow, decreases cell death and improves behavioral recovery. These data further support the role of glutamate in the pathogenesis of ischemic damage in brain and demonstrate that targeted gene delivery to decrease the ischemia-induced glutamate overflow reduces the cellular and behavioral deficits caused by stroke.
    PLoS ONE 01/2011; 6(8):e22135. · 3.73 Impact Factor
  • M.J. Chiocco, B.K. Harvey, Y. Wang, B.J. Hoffer
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    ABSTRACT: Parkinson's disease (PD) is a slowly progressive disorder with no known etiology. Pathologically, there is a loss of the dopaminergicneurons in the substantia nigra that project to the striatum. Current available therapies for PD are targeted to the restoration of striataldopamine. These approaches may alleviate symptoms transiently, but fail to slow the progression of disease. One emergent therapeuticapproach is the use of neurotrophic factors to halt or reverse the loss of dopaminergic neurons. There have been intensive researchefforts both preclinically and clinically testing the efficacy and safety of neurotrophic factors for the treatment of PD. In this review, wediscuss the neuroprotective and neuroregenerative properties of various trophic factors, both old and recent, and their status as therapeuticmolecules for PD
    Parkinsonism & Related Disorders 01/2007; 13:S321-S328. · 3.27 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Parkinson's disease (PD) is a slowly progressive disorder with no known etiology. Pathologically, there is a loss of the dopaminergic neurons in the substantia nigra that project to the striatum. Current available therapies for PD are targeted to the restoration of striatal dopamine. These approaches may alleviate symptoms transiently, but fail to slow the progression of disease. One emergent therapeutic approach is the use of neurotrophic factors to halt or reverse the loss of dopaminergic neurons. There have been intensive research efforts both preclinically and clinically testing the efficacy and safety of neurotrophic factors for the treatment of PD. In this review, we discuss the neuroprotective and neuroregenerative properties of various trophic factors, both old and recent, and their status as therapeutic molecules for PD.
    Parkinsonism & Related Disorders 01/2007; 13 Suppl 3:S321-8. · 3.27 Impact Factor