Modulation of brain function by targeted delivery of GABA through the disrupted blood-brain barrier
2019
Abstract The technology of transcranial focused ultrasound (FUS) enables a novel approach to
neuromodulation, a tool for selective manipulation of brain function to be used in neurobiology research and with potential applications in clinical treatment. The method uses transcranial focused ultrasound to non-invasively open the blood-brain barrier (BBB) in a localized region such that a systemically injected neurotransmitter chemical can be delivered to the targeted brain site. The approach modulates the chemical signaling that occurs in and between neurons, making it complimentary to most other
neuromodulationtechniques that affect the electrical properties of neuronal activity. Here, we report delivering the inhibitory neurotransmitter GABA to the right somatosensory cortex of the rat brain during bilateral hind paw electrical stimulation and measure the inhibition of activation using functional MRI (fMRI). In a 2 × 2 factorial design, we
evaluated conditionsof BBB Closed vs BBB Open and No GABA vs GABA . Results from fMRI measurements of the
blood oxygen level-dependent(
BOLD) signal show: 1) intravenous GABA injection without FUS-mediated BBB opening does not have an effect on the
BOLDresponse; 2) FUS-mediated BBB opening alone significantly alters the
BOLDsignal response to the stimulus, both in amplitude and shape of the time course; 3) the combination of FUS-mediated BBB opening and GABA injection further reduces the peak amplitude and spatial extent of the
BOLDsignal response to the stimulus. The data support the thesis that FUS-mediated opening of the BBB can be used to achieve non-invasive delivery of neuroactive substances for targeted manipulation of brain function.
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