Table 2.

The Use of Optogenetics in CNS Injuries

Diseases	Application directions	Topics	Targets	Reference
TBI	An experimental tool: assessing and monitoring nerve cells	Neurogliovascular dysfunction in TBI	Pyramidal neuron	Adams et al. 201861
		Early activity loss of ipsilesional motor cortex after mTBI	Motor cortex	Nguyen et al. 202162
		Monitoring in critically neurologically impaired patients	Specific regions and circuits	Jones et al. 201663
	An experimental tool: altering neuronal activity	Studying or verifying the function of neural circuits in TBI models	Specific neurons	Krukowski et al. 2021; Ndode-Ekane et al. 2021; Chever et al. 2021; Mester et al. 2021; Zeng et al. 202064-68
		The timing of Raf/ERK and AKT activation in protecting PC12 cells	Raf/ERK and AKT pathways	Ong et al. 201669
	Potential to be intervention methods: TBI complications	Optical depolarization promoted cognitive recovery and maturation of newborn neurons	DCX-expressing cells	Zhao et al. 201873
SCI	Reducing damage to nerve cells	Optogenetic apoptosis: light-triggered cell death	Bax	Hughes et al. 201588
		Optogenetic control of cell differentiation in channelrhodopsin-2-expressing OS3	Glial progenitor cells	Ono et al. 201789
		Lentiviral IL-10 gene therapy preserves fine motor circuitry and function after a cervical SCI	Neural motor circuits	Chen et al. 202190
	Promoting functional recovery	Optogenetic modulation of neural progenitor cells improves neuroregenerative potential	Spinal-cord-derived neural precursor cells	Giraldo et al. 202092
		Reducing pericyte-derived scarring promotes recovery after SCI	Cervical spinal cord rostral to a dorsal hemisection	Dias et al. 201894
		Neural stem cell grafts form extensive synaptic networks that integrate with host circuits after SCI	Corticospinal tract axons	Ceto et al. 202095
		Optical control of muscle function by transplantation of motor neurons	Motor neurons	Bryson et al. 201496
		Optogenetic control of nerve growth	Dorsal root ganglia	Park et al. 201597
		Optogenetic neuronal stimulation promotes functional recovery after SCI	Glutamatergic neurons	Deng et al. 202199
		Restoring function after SCI injury by bioluminescent-optogenetics.	Neurons	Petersen et al. 2021101
Stroke	Neuroplastic and neuroprotective effects in the sensorimotor cortex	Optogenetic neuronal stimulation promotes functional recovery after stroke	Layer V of the ipsilateral primary motor cortex	Chen et al. 2014120
		Cholinergic upregulation by optogenetic stimulation	Nucleus basalis	Mirza Agha et al. 2021121
		Optogenetics stimulates nerve reorganization in the contralesional anterolateral primary motor cortex	Contralesional anterolateral primary motor cortex	Gao et al. 2022125
		Optogenetic excitation of ipsilesional sensorimotor neurons is protective	Ipsilesional sensorimotor neurons	Bo et al. 2019126
		Neurovascular coupling impairment in acute ischemic stroke by optogenetics	Ipsilesional sensorimotor cortex	Bo et al. 2020128
		Gamma frequency stimulation attenuates vascular and behavioral dysfunction	Inhibitory neurons	Balbi et al. 2021129
		Mild stimulation improves neuronal survival in an in vitro model	Penumbral neurons	Muzzi et al. 2019130
	Cellular replacement therapies for nerve repair	Optogenetic stimulation of neural grafts enhances neurotransmission and downregulates the inflammatory response	Neural stem cells	Daadi et al. 2016131
		Optochemogenetic stimulation of transplanted iPS-NPCs enhances neuronal repair and functional recovery	Neural progenitor cells	Yu et al. 2019132
		Optogenetic stimulation of glutamatergic neuronal activity in the striatum enhances neurogenesis in the subventricular zone	Glutamatergic neurons in the striatum	Song et al. 2017136
		Optogenetic inhibition of striatal neuronal activity improves the survival of transplanted neural stem cells and neurological outcomes	Striatal neurons	Lu et al. 2017137
		Optical inhibition of striatal neurons promotes focal neurogenesis and neurobehavioral recovery	Striatal neurons	(He et al. 2017)138
		Optogenetic inhibition of striatal GABAergic neuronal activity improves outcomes after stroke	GABAergic neurons	Jiang et al. 2017140
	Afferent and efferent neural circuits for improved functional recovery	Optogenetic neuronal stimulation promotes persistent functional recovery after stroke	Contralesional lateral cerebellar nucleus	Shah et al. 2017142
		Optogenetic stimulation reduces neuronal nitric oxide synthase expression after stroke	Contralesional lateral cerebellar nucleus	Pendharkar et al. 2021145
		Optogenetic rewiring of thalamocortical circuits to restore function in the stroke injured brain	Thalamocortical axons	Tennant et al. 2017147
		Closed-loop optogenetic control of thalamus interrupts seizures after cortical injury	Thalamocortical circuits	Paz et al. 2013148
	Combination with other rehabilitation therapies	Slow waves promote sleep-dependent plasticity and functional recovery after stroke	Pyramidal neurons	Facchin et al. 2020153
		Environmental enrichment implies GAT-1 as a potential therapeutic target for stroke recovery		Lin et al. 2021156
		The neuronal activation is essential for environmental enrichment-induced post-stroke motor recovery	Deep cerebellar nuclei	Zhang et al. 2019157

GABA, gamma aminobutyric acid; IL, interleukin; iPC-NPC, induced pluripotent-stem-cell-derived neural progenitor cell; SCI, spinal cord injury; TBI traumatic brain injury.