Experimental assessment of the safety and potential efficacy of high irradiance photostimulation of brain tissues

Abstract

Optogenetics is widely used in fundamental neuroscience. Its potential clinical translation for brain neuromodulation requires a careful assessment of the safety and efficacy of repeated, sustained optical stimulation of large volumes of brain tissues. This study was performed in rats and not in non-human primates for ethical reasons. We studied the spatial distribution of light, potential damage, and non-physiological effects in vivo, in anesthetized rat brains, on large brain volumes, following repeated high irradiance photo-stimulation. We generated 2D irradiance and temperature increase surface maps based on recordings taken during optical stimulation using irradiance and temporal parameters representative of common optogenetics experiments. Irradiances of 100 to 600 mW/mm2 with 5 ms pulses at 20, 40, and 60 Hz were applied during 90 s. In vivo electrophysiological recordings and post-mortem histological analyses showed that high power light stimulation had no obvious phototoxic effects and did not trigger non-physiological functional activation. This study demonstrates the ability to illuminate cortical layers to a depth of several millimeters using pulsed red light without detrimental thermal damages.

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“…Implantation of LEDs or a fiber requires the light output to be proportionally higher than necessary to activate ChR2 because of light scattering properties in brain tissue. One study using a fiber to deliver light reported that local tissue temperature increased by 0.8 °C (Senova et al, 2017). Interestingly in that study, no effect was seen on neuronal cell death with acute light applications at the highest illumination used (Senova et al, 2017), however the question still remains how the tissue can handle local heating with longer duration or repeated applications.…”

“…In addition, attenuation of light occurs through absorption and scattering in brain tissue, resulting in the need for higher intensities of light at the source. This illumination often results in enhanced local temperatures, a consequence that is greater with stronger and more frequent irradiance (Senova et al, 2017), and can lead to as much as a 30% increase in local neuron firing rates (Stujenske et al, 2015). Lastly, glial scarring can occur at the light source (Podgorski and Ranganathan, 2016), decreasing effective light intensities and leading to variability in neuronal control.…”

Opto nongenetics inhibition of neuronal firing

“…It should be noted that we expect to reduce the effects of light on MC firing by decreasing light power and by increasing light wavelength (Stujenske et al, ; Senova et al., ); what would probably reduce the ES when using a light power lower than 13 mW (the one used in the pilot experiments). For n = 30 sweeps in the neuron by neuron analysis and n = 20 neurons in the population analysis, the statistical power becomes lower than 0.9 for ES < 0.54 and ES < 0.68 respectively.…”

LED‐based red light photostimulation improves short‐term response of cooled boar semen exposed to thermal stress at 37°C

“…The photostimulation has been applied to different fields. In studies of neuroscience, has been shown the existence of an activating effect of light irradiation on brain tissue, which in turn is able to modify the whole neural activity of the irradiated area (Senova et al, ; Valley, Wagner, Gallarda, & Lledo, ). Otherwise, the use of low‐level laser therapy (600–700 nm) is a very useful tool for improving the proliferation rate of various cell lines, being applied for this purpose in fields such as tissue engineering and regenerative medicine (AlGhamdi, Kumar, & Moussa, ).…”