Longitudinal Brain Size Measurements in App/Ps1 Transgenic Mice

Vincent, Trevor; Thiessen, Jonathan D.; Kurjewicz, Laryssa M.; Germscheid, Shelley; Turner, Allan; Zhilkin, Peter; Alexander, Murray E.; Martin, Melanie

doi:10.4137/mri.s5885

Cited by 13 publications

(8 citation statements)

References 31 publications

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“…We performed calculations under the assumption that the maximum average volume of an adult C57BL/6 male brain is approximately 460 mm 3 , which is the equivalent of 460 μl. 31 Thus, from the established concentration of 1 ng/25 μl, we calculated the total effective dose to be 18.4 ng. Furthermore, intranasal administration allows for a direct passage into the brain, allowing for greater distribution into the brain parenchyma.…”

Section: Methodsmentioning

confidence: 99%

Neuroprotective and regenerative roles of intranasal Wnt-3a administration after focal ischemic stroke in mice

Wei

Zhang

Taylor

et al. 2017

J Cereb Blood Flow Metab

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Wnt signaling is a conserved pathway involved in expansion of neural progenitors and lineage specification during development. However, the role of Wnt signaling in the post-stroke brain has not been well-elucidated. We hypothesized that Wnt-3a would play an important role for neurogenesis and brain repair. Adult male mice were subjected to a focal ischemic stroke targeting the sensorimotor cortex. Mice that received Wnt-3a (2 µg/kg/day, 1 h after stroke and once a day for the next 2 days, intranasal delivery) had reduced infarct volume compared to stroke controls. Wnt-3a intranasal treatment of seven days upregulated the expression of brain-derived growth factor (BDNF), increased the proliferation and migration of neuroblasts from the subventricular zone (SVZ), resulting in increased numbers of newly formed neurons and endothelial cells in the peri-infarct zone. Both the molecular and cellular effects of Wnt-3a were blocked by the Wnt specific inhibitors XAV-939 or Dkk-1. In functional assays, Wnt-3a treatment enhanced the local cerebral blood flow (LCBF) in the peri-infarct, as well as improved sensorimotor functions in a battery of behavioral tests. Together, our data demonstrates that the Wnt-3a signaling can act as a dual neuroprotective and regenerative factor for the treatment of ischemic stroke.

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Section: Methodsmentioning

confidence: 99%

Neuroprotective and regenerative roles of intranasal Wnt-3a administration after focal ischemic stroke in mice

Wei

Zhang

Taylor

et al. 2017

J Cereb Blood Flow Metab

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“…3,29 As a result, the total volume of macromolecules that can be infused was limited to 0.8 ml and CED was not performed. Nevertheless, it is reasonable to expect enhanced diffusion in brains pre-conditioned with FUS and microbubbles when CED-based infusion is applied.…”

Section: Discussionmentioning

confidence: 99%

Direct brain infusion can be enhanced with focused ultrasound and microbubbles

Wang

Karakatsani

Fung

et al. 2016

J Cereb Blood Flow Metab

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The delivery of most therapeutic agents is rendered ineffective for the treatment of brain diseases due to the presence of the blood-brain barrier (BBB). The goal of this study was to investigate the effect of pre-infusion focused ultrasound (FUS) and microbubbles on the distribution of direct brain infusion in vivo. A single-element FUS transducer was used in all sonications, which were carried out immediately prior to direct infusion procedures. Mice received direct infusion of either Gadolinium-labeled albumin (Gd-albumin, 74 kDa) or adeno-associated virus (AAV, $4 MDa). The volumes of Gd-albumin at 30 min were deemed comparable (P ¼ 0.334) between the direct infusion (DI)-only group and the FUS þ DI group. At 120 min, the FUS þ DI group showed significantly higher contrast-enhanced volume (9.76 AE 0.74 mm 3 ) than the DI-only group (7.14 AE 0.34 mm 3 ). For mice infused with AAV, the total volume of transduction was estimated as GFP-positive regions and FUS þ DI group demonstrated significantly higher (P ¼ 0.017) transduction efficiency in vivo. In conclusion, enhanced bio-distribution of directly infused agents was observed when the targeted region was pre-conditioned with FUS and microbubbles. Focused ultrasound has the potential, as an adjuvant technique, to significantly enhance direct brain infusion and achieve the desired therapeutic outcomes.

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“…The mouse brain contains ~7.5 × 10 7 neurons in a volume of ~420 mm 3 (Vincent et al, 2010) and weighs about 0.5 g. The packing density of neurons varies widely between brain regions. In the below, we will use a cell density of ρ neurons ≈ 92,000/mm 3 , as measured for mouse cortex (Braitenberg and Schüz, 1991).…”

Section: Basic Constraintsmentioning

confidence: 99%

Physical principles for scalable neural recording

Marblestone

Zamft

Maguire

et al. 2013

Front. Comput. Neurosci.

225

223

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Simultaneously measuring the activities of all neurons in a mammalian brain at millisecond resolution is a challenge beyond the limits of existing techniques in neuroscience. Entirely new approaches may be required, motivating an analysis of the fundamental physical constraints on the problem. We outline the physical principles governing brain activity mapping using optical, electrical, magnetic resonance, and molecular modalities of neural recording. Focusing on the mouse brain, we analyze the scalability of each method, concentrating on the limitations imposed by spatiotemporal resolution, energy dissipation, and volume displacement. Based on this analysis, all existing approaches require orders of magnitude improvement in key parameters. Electrical recording is limited by the low multiplexing capacity of electrodes and their lack of intrinsic spatial resolution, optical methods are constrained by the scattering of visible light in brain tissue, magnetic resonance is hindered by the diffusion and relaxation timescales of water protons, and the implementation of molecular recording is complicated by the stochastic kinetics of enzymes. Understanding the physical limits of brain activity mapping may provide insight into opportunities for novel solutions. For example, unconventional methods for delivering electrodes may enable unprecedented numbers of recording sites, embedded optical devices could allow optical detectors to be placed within a few scattering lengths of the measured neurons, and new classes of molecularly engineered sensors might obviate cumbersome hardware architectures. We also study the physics of powering and communicating with microscale devices embedded in brain tissue and find that, while radio-frequency electromagnetic data transmission suffers from a severe power–bandwidth tradeoff, communication via infrared light or ultrasound may allow high data rates due to the possibility of spatial multiplexing. The use of embedded local recording and wireless data transmission would only be viable, however, given major improvements to the power efficiency of microelectronic devices.

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Longitudinal Brain Size Measurements in App/Ps1 Transgenic Mice

Cited by 13 publications

References 31 publications

Neuroprotective and regenerative roles of intranasal Wnt-3a administration after focal ischemic stroke in mice

Neuroprotective and regenerative roles of intranasal Wnt-3a administration after focal ischemic stroke in mice

Direct brain infusion can be enhanced with focused ultrasound and microbubbles

Physical principles for scalable neural recording

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