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Table 3 Preclinical usage of TNS in pathological conditions

From: Trigeminal nerve stimulation: a current state-of-the-art review

Model

Stimulation Method and Target

Species

Stimulation Parameters

Effect

Reference

Epilepsy

Infraorbital unilateral or bilateral electrostimulation

Adult female Long-Evans hooded rats

C1 – 333 Hz

3 – 11 mA

0.5 ms PW

↓Seizure frequency and severity

Bilateral stimulation is more effective than unilateral at the same intensity

Fanselow et al. 2000

Bilateral percutaneous electrical on ophthalmic nerves

Adult male Sprague–Dawley rats

140 Hz

10 mA

0.5 ms PW

1 min on, 4 min off

↓ Hippocampal apoptosis

↓ Neuroinflammation

Wang et al. 2016

Unilateral electrical left infraorbital nerve

Adult male Sprague–Dawley rats

30 Hz

2 mA

0.5 ms PW

30 s on, 5 min off

↑ Mild seizure duration

↓ Severe seizure duration

Activation in Sol, LCC, DR, amygdala, endopiriform nucleus, hippocampus, entorhinal cortex, somatosensory cortex

Marcante et al., Mercante et al. 2017

Subarachnoid Hemorrhage with CBF reduction

Invasive Electrical

Pittmann-Moore pigs

45 Hz

0.2 ms PW

3 h continuous

↑ CBF; ↓ CVR

Salar et al. 1992

Subarachnoid Hemorrhage

Non- Invasive, Transcorneal, Nasociliary Nerve

Male albino Wistar rats

30 Hz

3 mA

1 ms PW

30 s continuous

↑ CBF at the MCA; ↓ CVR; ↑ ABP

Atalay et al. 2002

Subarachnoid Hemorrhage – Endovascular Puncture

Percutaneous Electrical, Infraorbital Nerve

Male Sprague–Dawley rats

50 Hz

0.5 – 2.5 V

20 s every 5 min for 60 min

↑ CBF; ↑ CSF CGRP

↓ Macro-and micro-vascular vasospasm

↓ Parenchymal microthrombi

↓ Apoptosis

↓ Neurobehavioral deficits

Shah et al., 2022

Ischemic Stroke—Middle Cerebral Artery Occlusion

Subcutaneous Electrical/Cold Temp Forehead Stimulation

Male Sprague–Dawley rats

25 Hz

0.06 mA

0.5 ms PW

Both:

↓ Focal ischemic infarctions

Cold Temp:

↑ MAP; ↑ HR

Shiflett et al. 2015

Traumatic Brain Injury

Invasive and Subcutaneous Electrical

Male Sprague–Dawley rats

1 min on per 11 min

TBI:

↑ CBF; ↑ MAP; ↑ PP; ↑ HR; ↑ PbrO2; ↓ RR

w/out TBI:

↑ CBF, ↓CVR

Chiluwal et al. 2017

Electrical acupuncture on infraorbital nerve

B6 mice

10 Hz

0.1 mA

200 ms PW

30 s on 30 s off for 60 min

↓ Edema; ↑ BOLD

↓ Sensorimotor dysfunction

↑ WGMT scores

↓ Inflammation

Yang et al. 2022

Infraorbital nerve

Mice

40 Hz

0.2 mA

200 ms PW

30 s on 30 s off for 60 min

↓ APP and Iba1 in HPC

↑ Dopaminergic activation

Xu et al. 2023

Traumatic Brain Injury-induced Loss of Consciousness

Bilateral electrical anterior ethmoidal nerve

Male Sprague–Dawley rats

140 Hz

1 mA

10 s on, 5 s off for 30 min

↑ Consciousness levels

↑ EEG voltage

↑ Hypocretin expression

↑ LH neuron activation

Sp5 glutamatergic neuron activation

Zheng et al. 2021

Traumatic Brain Injury Complicated by Hemorrhagic Shock

Percutaneous electrical, infraorbital and anterior ethmoid branches of trigeminal nerve

Male Sprague–Dawley rats

50 Hz

5 s PW

20 ms between pulses

5 s on, 5 s off for 1 min every 10 min, for total of 60 min

CBF oscillation

↑ Survival rate

↓ Lesion volume

↑ eNOS; ↓ iNOS

↓ Neuroinflammation

Li et al. 2021a, b

Hemorrhagic Shock

Percutaneous Electrical, Infraorbital Nerve

Male Sprague–Dawley rats

25 Hz

7 V

0.5 ms PW

↑CBF

↑MAP

↑PbO2

↑Survival time

↑Norepinephrine

↓Systemic inflammatory markers

Li et al. 2019