The central theme of this proposal is a clinically oriented research program dedicated to the noninvasive in vivo analysis of cerebral blood flow (CBF) and metabolism directed towards an understanding of the pathophysiology of stroke. The objectives of this theme will be accomplished by the application of 31PNMR and 1HNMR spectroscopy, and 1HNME imaging to the study of brain anatomy, blood flow and energy metabolism in well defined animal and clinical research protocols. The overall goal is to use these techniques to identify cellular in mechanisms and cerebral hemodynamic and metabolic markers which permit the logical and safe therapy of cerbral vascular disease. We have emphasized the exploration of pathophysiological mechanisms of cerbral ischemia and in so doing sought to identify intrinsic cellular protective mechanisms that might be manipulated to improve neurological outcome from stroke. More specifically, we seek to continue our efforts towards developing anew NMR technique for measuring regional CBF in animals, suitable for interleaving with 31PNMR or 1H spectroscopy, and eventual successful NMR imaging of CBF in patients. In an experimental animal proposal, the physical factor of thermal change is investigated for beneficial or adverse effects on brain metabolism. Within the project is a study of stress proteins to evaluate one endpoint through which the brain may induce intrinsic protection against the interactive effects of temperature and ischemia. We will also study the serial changes in brain energy metabolism and acid-base status in acute focal hemispheric ischemic stroke and global ischemia due to cardiac arrest. The significance of the previously observed """"""""flip-flop"""""""" from brain acidosis to alkalosis is evaluated by recording its associations with brain blood flow, energy status, edema, structural damage and neurological outcome. The influence of blood glutose on brain metabolism and pH will also be evaluted and the possible therapeutic window that the """"""""flip-flop"""""""" phenomenon could potentially identically identify is tested by a therapeutic strategy; to tightly control systemic glucose limit ischemic brain acidosis and improve neurological outcome. Finally we will study vascular dementia and seek to identify metabolic markers to distinguish this dementia subtype from typical degenerative dementia of Alzheimer type. These metabolic marker will be followed over time to test their resilience in differential diagnosis as well as to evaluate progressive metabolic changes in vascular dementia compared to Alzheimer dementia.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Program Projects (P01)
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Neurological Disorders Program Project Review A Committee (NSPA)
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Henry Ford Health System
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Knight, R A; Nagaraja, T N; Li, L et al. (2016) A Prospective Safety Trial of Atorvastatin Treatment to Assess Rebleeding after Spontaneous Intracerebral Hemorrhage: A Serial MRI Investigation. Austin J Cerebrovasc Dis Stroke 3:
Ding, Guang-Liang; Chopp, Michael; Li, Lian et al. (2014) Magnetic Resonance Imaging of Stroke in the Rat. Bo Pu Xue Za Zhi 31:116-132
Pindolia, Kirit; Li, Hong; Cardwell, Cisley et al. (2014) Characterization and functional analysis of cellular immunity in mice with biotinidase deficiency. Mol Genet Metab 112:49-56
Cui, Xu; Chopp, Michael; Zacharek, Alex et al. (2013) The neurorestorative benefit of GW3965 treatment of stroke in mice. Stroke 44:153-61
Zhang, Rui Lan; Zhang, Zheng Gang; Chopp, Michael (2013) Targeting nitric oxide in the subacute restorative treatment of ischemic stroke. Expert Opin Investig Drugs 22:843-51
Yan, Tao; Chopp, Michael; Ning, Ruizhuo et al. (2013) Intracranial aneurysm formation in type-one diabetes rats. PLoS One 8:e67949
Hernández-Vázquez, A; Wolf, B; Pindolia, K et al. (2013) Biotinidase knockout mice show cellular energy deficit and altered carbon metabolism gene expression similar to that of nutritional biotin deprivation: clues for the pathogenesis in the human inherited disorder. Mol Genet Metab 110:248-54
Xiong, Ye; Mahmood, Asim; Chopp, Michael (2013) Animal models of traumatic brain injury. Nat Rev Neurosci 14:128-42
Wang, Shiyang; Chopp, Michael; Nazem-Zadeh, Mohammad-Reza et al. (2013) Comparison of neurite density measured by MRI and histology after TBI. PLoS One 8:e63511
Santra, Manoranjan; Chopp, Michael; Zhang, Zheng Gang et al. (2012) Thymosin ? 4 mediates oligodendrocyte differentiation by upregulating p38 MAPK. Glia 60:1826-38

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