Lakshminarayan V Chinta

Publications (3)20.81 Total impact

• Article: Amyloid-β-dependent compromise of microvascular structure and function in a model of Alzheimer's disease.

  Adrienne Dorr, Bhupinder Sahota, Lakshminarayan V Chinta, Mary E Brown, Aaron Y Lai, Keran Ma, Cheryl A Hawkes, Joanne McLaurin, Bojana Stefanovic
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  ABSTRACT: The majority of patients with Alzheimer's disease have cerebral amyloid angiopathy, thus showing deposition of amyloid-β peptides in the walls of leptomeningeal and cortical arterioles. These deposits are believed to result from impaired clearance of parenchymal amyloid-β peptides. In the current work, we examined the changes in cortical microvascular structure and function in situ in TgCRND8, a transgenic mouse model of Alzheimer's disease. In contrast to venules, cortical arterioles were shown to increase in tortuosity and decrease in calibre with amyloid-β peptide accumulation. These structural changes were accompanied by progressive functional compromise, reflected in higher dispersion of microvascular network transit times, elongation of the transit times, and impaired microvascular reactivity to hypercapnia in the transgenic mice. Moreover, inhibition of amyloid-β peptide oligomerization and fibrillization via post-weaning administration of scyllo-inositol, a naturally occurring stereoisomer of myo-inositol, rescued both structural and functional impairment of the cortical microvasculature in this Alzheimer's disease model. These results demonstrate that microvascular impairment is directly correlated with amyloid-β accumulation and highlight the importance of targeting cerebrovascular amyloid angiopathy clearance for effective diagnosis, monitoring of disease progression and treatment of Alzheimer's disease.
  Brain 10/2012; 135(Pt 10):3039-50. · 9.46 Impact Factor
• Article: Robust quantification of microvascular transit times via linear dynamical systems using two-photon fluorescence microscopy data.

  Lakshminarayan V Chinta, Liis Lindvere, Bojana Stefanovic
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  ABSTRACT: Vascular transit time is an important indicator of microcirculatory health. We present a second-order-plus-dead-time (SOPDT) model for robust estimation of kinetic parameters characterizing microvascular bolus passage using two-photon fluorescence microscopy (2PFM) in anesthetized rats receiving somatosensory stimulation. This methodology enables quantification of transit time, time-to-peak, overshoot, and rate of bolus passage through the microvascular network. The overall transit time during stimulation, of 2.2±0.1 seconds, was shorter (P∼0.0008) than that at rest (2.7±0.2 seconds). When compared with conventional γ-variate modeling, the SOPDT modeling yielded better quality of fit both at rest (P<0.0001) and on activation (P<0.001).
  Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 06/2012; 32(9):1718-24. · 5.46 Impact Factor
• Article: Quantitative estimates of stimulation-induced perfusion response using two-photon fluorescence microscopy of cortical microvascular networks.

  Lakshminarayan V Chinta, Liis Lindvere, Adrienne Dorr, Bhupinder Sahota, John G Sled, Bojana Stefanovic
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  ABSTRACT: Functional hyperemia, or the increase in focal perfusion elicited by neuronal activation, is one of the primary functions of the neurovascular unit and a hallmark of healthy brain functioning. While much is known about the hemodynamics on the millimeter to tenths of millimeter-scale accessible by MRI, there is a paucity of quantitative data on the micrometer-scale changes in perfusion in response to functional stimulation. We present a novel methodology for quantification of perfusion and intravascular flow across the 3D microvascular network in the rat somatosensory cortex using two-photon fluorescence microscopy (2PFM). For approximately 96% of responding microvessels in the forelimb representation of the primary somatosensory cortex, brief (~2s) forepaw stimulation resulted in an increase of perfusion 20±4% (mean±sem). The perfusion levels associated with the remaining 4% of the responding microvessels decreased 10±9% upon stimulation. Vessels irrigating regions of lower vascular density were found to exhibit higher flow (p<0.02), supporting the notion that local vascular morphology and hemodynamics reflect the metabolic needs of the surrounding parenchyma. High dispersion (~77%) in perfusion levels suggests high spatial variation in tissue susceptibility to hypoxia. The current methodology enables quantification of absolute perfusion associated with individual vessels of the cortical microvascular bed and its changes in response to functional stimulation and thereby provides an important tool for studying the cellular mechanisms of functional hyperemia, the spatial specificity of perfusion response to functional stimulation, and, broadly, the micrometer-scale relationship between vascular morphology and function in health and disease.
  NeuroImage 04/2012; 61(3):517-24. · 5.89 Impact Factor