Table 2.
Characteristics of the included studies.
| Included studies | Animals | Timing of intervention | Protocol of VNS | Parameters of VNS (Frequency and Current and Pulse width) | Comparator (n = numbers in each group) | Outcomes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| TBI model | Sex | Weigh | Side of VNS (Cervical VN) | Duration | Behavioral test | Pathology | Mechanism | ||||
| Tang et al. (33) | Weight-drop TBI model, mouse | M | 250–300 g | 30 min after TBI | Left | One session, 15 min | 30 Hz, 1.0 mA, 0.5 ms |
TBI+VNS (n = 30); TBI+ sham VNS (n = 30); sham TBI (n = 30) | mNSS↓; | Brain water content↓, necrosis in lesioned brain tissues↓ | MDA↓; GSH↑; SOD↑; CAT↑; NLRP3↓, ASC↓, caspase-1↓; Bax↓; Bcl-2↑; IL-1β↓, IL-18↓, IL-6↓,TNF-α ↓ |
| Dong and Feng (31) | Weight-drop TBI model, rat | M, F | 250–300 g | 1 h after TBI | Left | One session, 15 min | 30 Hz, 1.0 mA, 0.5 ms |
Sham TBI (n = 30); TBI (n = 30); TBI+VNS (n = 30) | The level of consciousness↑ | None | orexin-A↑, OX1R↑ |
| Pruitt et al. (38) | CCI-TBI model, Rat |
F | 250–300 g | 3–4 weeks post-injury | Left | 5 weeks; two sessions/day, 30 min/session | 30 Hz, 0.8 mA, 0.1 ms |
TBI+VNS (n = 14); TBI (n = 14) | Maximal pull force↑ | Lesion size → | None |
| Zhou et al. (34) | Weight-drop TBI model, rabbit | M | 2.0–2.5 kg | 1 h after injury | Right | One session, 20 min | 5 Hz, 0.8 mA, 5 ms |
Blank control (n = 4); sham TBI (n = 6); TBI (n = 9); TBI+VNS (n = 8) | None | Brain water content↓ | TNF-α↓, IL-1β↓; IL-10↑ |
| Lopez et al. (32) | Weight-drop TBI model, mice | M | 20–24 g | None | Right | 10 min | -, 2 mA, - |
TBI+VNS(N = 4); TBI(n = 4); sham TBI(n = 4) | None | Neuronal degeneration and vacuolization in the neuropil in neocortex and hippocampal region CA1↓ | AQP-4↓ |
| Bansal et al. (30) | Weight-drop TBI model, mice | M | 20–24 g | None | Right | 10 min | -, 2 mA, - |
TBI+VNS(N = 8); TBI(n = 8); sham TBI(n = 8); | None | None | TNF-α↓, serum levels of Ghrelin↑, Tissue levels of Ghrelin↑ |
| Neese et al. (37) | FPI-TBI model, rat | M | 425–475 g | Initiated 24-h post-injury | Left | 30minfor the 14-day | 20 Hz, 0.5 mA, 0.5 ms |
TBI-VN(n = 8); TBI (n = 8); sham-TBI (n = 8) | None | None | GAD65/67-like cells in the rostral cerebral cortex ↑, GAD65/67-like cells in the hippocampal hilus → |
| Clough et al. (35) | FPI-TBI model, rat | M | 428 g | 2 h following FPI surgery | Left | Every 30 min for 48-h duration | 20 Hz, 0.5 mA, 0.5 ms |
TBI-VNS (n = 8); TBI (n = 6); sham TBI (n = 5) | BWT↑, LPT↑ | Brain water content ↓ | None |
| Smith et al. (36) | FPI-TBI, rat | M | 425–475 g | 2 h following FPI surgery | Left | Every 30 min 30 s stimulation for 14 days | 20 Hz, 0.5 mA, 0.5 ms |
TBI-VNS (n = 15); TBI (n = 15); sham TBI (n = 15) | SFRT↑, BWT↑, FFT↑, IP↑, LPT↑, MWM↑ | Cortical tissue loss →, degenerating neurons in the cerebral cortices, thalamus and basal ganglia →, Hippocampal pyramidal neuron death in the CA-3 of the dorsal hippocampus →, GFAP-stained cells → | None |
CCI, controlled cortical impact; FPI, fluid percussion; M, Male; F, Female; TBI, traumatic brain injury; VNS, Vagus nerve stimulation; mNSS, modified neurological severity score; SFRT, skilled forelimb reaching test; BWT, beam walk test; FFT, forelimb flexion test; IP, inclined plane; LPT, locomotor placing test; MWM, morris water maze test; GFAP, glial fibrillary acidic protein; MDA, malondialdehyde; GSH: glutathione; SOD, superoxide dismutase; CAT, catalase; NLRP3, nucleotide-binding domain (NOD)-like receptor protein 3; ASC, apoptosis-associated speck-like protein; Bax, Bcl-2-associated X; Bcl-2: B-cell lymphoma 2; IL-1β, interleukin−1β; IL-18, interleukin−18; IL-6, interleukin−6; TNF-α, tumor necrosis factor-α; OX1R, orexin receptor type 1; IL-10, BBB, blood-brain barrier; AQP-4, Aquaporin 4; GAD, glutamic acid decarboxylase; ↑, significantly increased in animals receiving VNS; ↓, significant decreased in animal receiving VNS; →, no statistically significant difference between groups.