Optogenetic Modulation for the Treatment of Traumatic Brain Injury

Abstract

Although research involving traumatic brain injury (TBI) has traditionally focused on the acute clinical manifestations, new studies provide evidence for chronic and progressive neurological sequelae associated with TBI, highlighting the risk of persistent, and sometimes lifelong , consequences for affected patients. Several treatment modalities to date have demonstrated efficacy in experimental models. However, there is currently no effective treatment to improve neural structure repair and functional recovery of TBI patients. Optogenetics represents a potential molecular tool for neuromodulation and monitoring cellular activity with unprecedented spatial resolution and millisecond temporal precision. In this review, we discuss the conceptual background and preclinical evidence of optogenetics for neuromodulation, and translational applications for TBI treatment are considered.

Advances in Optogenetics Applications for Central Nervous System Injuries

“…Constructing a corresponding transgenic animal model is a direct method. 33 , 34 In theory, all targeted cells could stably express opsins. But this way has some drawbacks.…”

“…The generation of transgenic lines is time-consuming and labor-intensive, and specific technical difficulties lead to high costs. 33 In addition, the low transcriptional activity of endogenous promoters would result in insufficient expression of opsin genes in target cells. 34 Nevertheless, many researchers still advocate this method because it can produce stable strains and needs no redundant operations on experimental animals.…”

“…Transfecting the constructed genome into targeted cells to express specific opsins through viral vectors is also popular 33 ( Fig. 1 ).…”

“… 42 This method is especially suitable for expressing opsins in cell types without defined promotor sequences, complements the way of AAVs carrying specific promters to infect targeted cells. 33 Cre-dependent promoters also overcome the low transcriptional activity of some cell-type-specific promoters. 33 This gene expression method combines transgenic animals with virus injection and is more convenient than only transgenic technology.…”

“… 33 Cre-dependent promoters also overcome the low transcriptional activity of some cell-type-specific promoters. 33 This gene expression method combines transgenic animals with virus injection and is more convenient than only transgenic technology.…”