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Table 1 Study characteristics

From: The effects of aerobic exercise on neuroimmune responses in animals with traumatic peripheral nerve injury: a systematic review with meta-analyses

Reference

Country

Study design

Species

Strain

Sex

Age

(weeks)

Weight

(g)

Disease model

Outcome measurement locations, side (if applicable)

Control group

(n)

Intervention group

(n)

Exercise start

(dpi)

Length exercise program

Session duration

Intensity

Almeida C 2015 [44]

Brazil

RCT

Mice

BALB/c

M

NR

23.5 ± 0.24

CCI

Sciatic nerve, unilateral

• Spinal cord dorsal horn L4–L6, ipsilateral

• DRG L4 and L5, ipsilateral

SED

(n = NR)

SE

(n = 8)

7

5 weeks

Increasing from 10 min up to 50 min

NA

Arbat-Plana A 2015 [21]

Spain

ECT

Rats

Sprague–Dawley

F

8

250–300

Nerve transectiona

Sciatic nerve, unilateral

Spinal cord segments L3–L6 (motoneuron pools), ipsilateral. For one outcome bilateral (ipsilateral data extracted)

SED

(n = 16)

IG1: TR High intensity

(n = 8)

3

5 days

Increasing:

up to 60 min

Increasing: 10 cm/s up to 30 cm/sec

IG2: TR Low intensity

(n = 8)

3

2 weeks

2 × 30 min,

10 min rest

10 cm/s

Arbat-Plana A 2017A [26]

Spain

ECT

Rats

Sprague–Dawley

F

8

250–300

Nerve transectiona

Sciatic nerve, unilateral

Spinal cord segments L3–L6 (motoneuron pools), ipsilateral. For one outcome bilateral (ipsilateral data extracted)

SED

(n = 4)

IG1: TR High intensity

(n = 4)

3

1.5 weeks

Increasing up to 60 min

10 cm/s, every 5 min + 2 cm/s to 30 cm/sec

IG2: TR Low intensity

(n = 4)

3

2 × 30 min,

10 min rest

10 cm/s

IG3: VWR

(n = 12)

0

voluntary

voluntary

Arbat-Plana A 2017B [27]

Spain

ECT

Rats

Sprague–Dawley

F

8

180–200

Nerve transectiona

Sciatic nerve, unilateral

Spinal cord section L4–5, Bilateral (ipsilateral data extracted)

SED

(n = 11)

TR

(n = 11)

3

1.5 weeks

Increasing up to 60 min

10 cm/s, every 5 min + 2 cm/s until 30 cm/sec

Arbat-Plana A 2019 [32]

Spain

ECT

Rats

Sprague–Dawley

F

8

200–280

Nerve transectiona

Sciatic nerve, unilateral

Spinal cord segments L3–L6, (motoneuron pools), ipsilateral. For one outcome bilateral (ipsilateral data extracted)

SED

(n = 9)

TR

(n = 9)

3

12 days

60 min

10 cm/s, every 5 min + 2 cm/s until 30 cm/sec

Ashour H 2017 [46]

Egypt

RCT

Rats

Albino

M

Adult, age unspecified

120–150

SNI

Sciatic nerve, unilateral

• Serum

• Fascia surrounding nerve bifurcation, ipsilateral

• Gastrocnemius muscle, ipsilateral

• Sciatic nerve, ipsilateral

SED

(n = 8)

SE

(n = 8)

NR

5 days

Increasing from 20 up to 90 min

NA

Bobinski F 2011 [54]

Brazil

ECT

Mice

Swiss

M

8–9

25–35

Nerve crush injury

Sciatic nerve, unilateral

• Lumbar spinal cord (L1–L6), side not specified

• Sciatic nerve, ipsilateral

SED

(n = 8)

TR

(n = 8)

3

2 weeks

30 min

10 m/min, 0% inclination

Bobinski F 2015 [55]

Brazil and USA

ECT

Mice

Swiss

M

8–9

25–35

Nerve crush injury

Sciatic nerve, unilateral

Brainstem / Raphe Pallidus (RPa) / Raphe Magnus (RMg) / Raphe Obscurus (ROb)

SED

(n = 8)

TR

(n = 8)

3

2 weeks

30 min

10 m/min, 0% inclination

Bobinski F 2018 [49]

Brazil and USA

ECT

Mice

Swiss

 + 

Balb/cJ wild type

M

NR

20–30

Nerve crush injury

Sciatic nerve, unilateral

• Lumbar spinal cord dorsal horn L1–L6 (specifically in laminae I–II and III–VI for some analyses), bilateral (ipsilateral data extracted)

• Whole lumbar portion of the spinal cord L1–L6 for some analyses, side not specified

• Sciatic nerve, ipsilateral

SED

(n = 8)

TR

(n = 8)

3

2 weeks

30 min

10 m/min, 0% inclination

Bonetti L 2016 [23]

Brazil

RCT

Rats

Wistar

M

12

280–330

Nerve crush injury

Sciatic nerve, unilateral

Lumbar spinal cord dorsal horn L4–L6, laminae II–IV, ipsilateral

SED

(n = 6)

TR

(n = 6)

2

5 weeks

Increase:

20 up to 60 min

5 min 30% MET (5.5 m/min),

10–50 min 45–55% of MET (9 m/min),

5 min 30% MET

Byun Y 2005 [38]

South Korea

RCT

Rats

Sprague–Dawley

M

6

200 ± 10

Nerve crush injury

Sciatic nerve, unilateral

Sciatic nerve, ipsilateral

SED

(n = 8)

TR

(n = 8)

3

12 days

30 min

8 m/min, 0% incline

Chen YW 2012 [29]

Taiwan

ECT

Rats

Sprague–Dawley

M

NR

250–300

CCI

Sciatic nerve, unilateral

Sciatic nerve, ipsilateral

SED

(n = 5)

IG1: SE

(n = 5)

2

39 days

90 min

From 9 × 10 min to 1 × 90 min

IG2: TR

(n = 5)

2

6 weeks

Increasing from 15–30 min to 60 min

1st week 1.2 km/h, then 1.8 km/h

Cobianchi S 2013 [24]

Spain

RCT

Rats

Sprague–Dawley

F

Adult, age unspecified

240 ± 30

Nerve transectiona

Sciatic nerve, unilateral

• Spinal cord ventral horn, ipsilateral

• DRG L4–L5, ipsilateral

SED

(n = 15)

TR

(n = 8)

3

5 days

60 min

Increasing: 10 cm/s up to 32 cm/s

Coradini JG 2015 [33]

Brazil

RCT

Rats

Wistar

M

10.4

NR

CCIb

Median nerve, unilateral

Median nerve, ipsilateral

SED

(n = 8)

SE

(n = 8)

3

3 weeks

Increasing from 20 min up to 40 min

Overload of 10% body weight while swimming

Farzad B 2018 [34]

Iran

RCT

Rats

Wistar

M

Adult, age unspecified

180–220

CCI

Sciatic nerve, unilateral

Spinal cord segments L4–L6, ipsilateral

SED

(n = 7)

SE

(n = 7)

3

4 weeks

Increasing duration from bouts of 10 min up

NA

Huang PC 2017 [28]

Taiwan

RCT

Rats

Sprague–Dawley

M

NR

220–270

CCI

Sciatic nerve, unilateral

Sciatic nerve, side not specified

SED

(n = 22)

TR

(n = 22)

8

3 weeks

30 min

14–16 m/min, 8% incline

Hung CH 2016 [36]

Taiwan

RCT

Rats

Sprague–Dawley

M

NR

220–270

CCI

Sciatic nerve, unilateral

• Spinal cords L4–L5, side not specified

• Spinal cords dorsal horn L4–L5, ipsilateral

SED

(n = 10)

TR

(n = 10)

3

4 weeks

30 min

14 -16 m/min, 8% incline

Kami K 2016A [20] Japan

ECT

Mice

C57BL/6 J

M

10

NR

PSL

Sciatic nerve, unilateral

Brain, lVTA,, bilateral (contralateral data extracted)

SED

(n = 5)

VWR

(n = 5)

NR

15 days

voluntary

voluntary

Kami K 2016B [30] Japan

ECT

Mice

C57BL/6 J

M

12

NR

PSL

Sciatic nerve, unilateral

Lumbar spinal cord dorsal horn L4–5, bilateral (ipsilateral data extracted)

SED

(n = 6)

TR

(n = 6)

2

5 days

60 min

7 m/min

Kami K 2016C [31]

Japan

ECT

Mice

C57BL/6 J

M

13

NR

PSL

Sciatic nerve, unilateral

Lumbar spinal cord dorsal horn L4–5, bilateral (ipsilateral data extracted)

SED

(n = 6)

TR

(n = 6)

2

5 days

60 min

7 m/min

Kim JE 2020 [37] Korea

ECT

Rats

Sprague–Dawley

M

6

160

Nerve crush injury

Sciatic nerve, unilateral

Sciatic nerve, ipsilateral

CG1: SED 7 days

(n = 10)

IG1: TR 7 days

(n = 10)

3

1 week

20 min

8 m/min

CG2: SED 14 days

(n = 10)

IG2: TR 14 days

(n = 10)

3

2 weeks

20 min

8 m/min

Kim S 2013 [35]

Korea

RCT

Rats

Sprague–Dawley

M

4

NR

Nerve transection

Sciatic nerve, unilateral

• Serum

• Liver

• Gastrocnemius, soleus and tibialis anterior muscles, side unspecified

SED

(n = 6)

TR

(n = 6)

7

4 weeks

25–30 min

15 m/min, 3–5% inclination

Kim YJ 2015 [25]

Korea

RCT

Rats

Sprague–Dawley

M

10

250–300

CCI

Sciatic nerve, unilateral

• Rostral ventral medulla

• Lumbar spinal cords (2 cm long), side unspecified

SED

(n = 11)

TR

(n = 11)

NR

4 weeks

40 min

Warm-up 5 min; Main exercise 30 min; Cool-down: 5 min

8 m/min for 5 min,

11 m/min for 5 min, 22 m/min for 20 min

Korb A 2010 [41]

Brazil

RCT

Rats

Wistar

M

16

200–250

Nerve transection

Sciatic nerve, unilateral

• Magnus raphe nucleus

• Dorsal raphe nucleus

• Lumbosacral ventral horn of spinal cord, bilateral (ipsilateral data extracted)

• Lumbosacral spinal cord dorsal horn, bilateral (ipsilateral data extracted)

SED

(n = 5)

TR

(n = 5)

7

4 weeks

20–60 min

30% of MET (5 min 5,5 m/min), 45–55% of MET (10-50 min at ~ 9 m/min), 30% of MET (5 min at 5,5 m/min)

Krakowiak J 2015 [53]

USA

ECT

Mice

C57BL/6 J wild type

F

 > 8

NR

Nerve transection

Sciatic nerve, unilateral

Spinal cord segments

L3–L6, (motoneurons), ipsilateral

SED

(n = 8)

TR

(n = 9)

3

2 weeks

28 min

20 m/min, 4 × 2 min/5 min rest

Liao CF 2017 [42]

Taiwan

RCT

Rats

Sprague–Dawley

M

9

201–225

Nerve transectiona

Sciatic nerve, unilateral

Spinal cord L4, ipsilateral

SED

(n = 10)

IG1: SE10

(n = 10)

7

3 weeks

10 min

NA

IG2: SE20

(n = 10)

7

3 weeks

20 min

NA

IG2: SE30

(n = 10)

7

3 weeks

30 min

NA

Liu C 2014 [57]

China and USA

RCT

Mice

C57BL/6 J

M + F

 > 2 months

18–32

Nerve transection

Sciatic nerve, unilateral

Spinal cord segments L3–L5, (motoneurons), ipsilateral

CG1: SED Male

(n = 4)

IG1: TR Male Continuous

(n = 4)

3

2 weeks

60 min

10 m /min

CG2: SED Female (n = 4)

IG2: TR Female Continuous

(n = 4)

3

2 weeks

60 min

10 m /min

CG1: SED Male

(n = 4)

IG3: TR Male Interval

(n = 4)

3

2 weeks

28 min:

4 × 2 min + 5 min rest

20 m / min

CG2: SED Female (n = 4)

IG4: TR Female Interval

(n = 4)

3

2 weeks

28 min:

4 × 2 min + 5 min rest

20 m / min

Lopes BC 2020 [58] Brazil

ECT

Rats

Wistar

M

8

280 ± 20

CCI

Sciatic nerve, unilateral

• Cerebral cortex

• Brainstem

• Spinal cord, level and side unspecified

SED

(n = 6)

TR

(n = 6)

15

8 days

20 min

70% VO2max, 0° incline

Lopez-Alvarez VM 2015 [40]

Spain

RCT

Rats

Sprague–Dawley

F

Adult, age unspecified

240 ± 30

Nerve transectiona

Sciatic nerve, unilateral

• Epidermal and subepidermal nerve fibers from footpad mid-plan skin sections, hind paws, ipsilateral. For 1 outcome bilateral (ipsilateral data extracted)

• Spinal cord segments L3–6, for some outcome bilateral (ipsilateral data extracted)

• Spinal cord dorsal horn L3 and L5, ipsilateral

• Dorsal Root Ganglion L3–L6, bilateral (ipsilateral data extracted)

• For one outcome Dorsal Root Ganglion L3, ipsilateral

SED

(n = 8)

IG1: TR1

(n = 8)

3

5 days

(day 3–7)

60 min

10 cm/s, + 2 cm/s every 5 min until 32 cm/s

IG2: TR2

(n = 7)

3

5 days

(day 10–14)

60 min

Lopez-Alvarez VM 2018 [51] Spain

RCT

Rats

Sprague–Dawley

F

Adult, age unspecified

240 ± 30

Nerve transectiona

Sciatic nerve, unilateral

• Brain, projection areas of injured side

• Lumbar spinal cord dorsal horn segments L4–L5, bilateral (ipsilateral data extracted)

SED

(n = 8)

TR

(n = 10)

3

12 days

60 min

10 cm/s, + 2 cm/s every 5 min until 32 cm/s

Martins DF 2018 [50] Brazil

ECT

Mice

Swiss

M

8

25–30

Nerve crush injury

Sciatic nerve, unilateral

• Sciatic nerve, ipsilateral

• Gastrocnemius and soleus muscles, side not specified

SED

(n = 8)

TR

(n = 8)

7

8 weeks

30 min

14 m/min, − 16° slope (downhill running)

Park JS 2014 [59] USA

RCT

Mice

C57BL/6 J

M

6–8

20–30

Nerve transectiona

Median and ulnar nerves, unilateral

• Median nerve, ipsilateral

• Forearm extrinsic finger flexor muscles, side unspecified

• Serum

SED

(n = 8)

TR

(n = 8)

4

6 weeks

60 min

10 m /min, 0° incline,

5 min warm up and cooldown at 6 m/min

Safakhah HA 2017 [45]

Iran

RCT

Rats

Wistar

M

Adult, age unspecified

220 ± 20

CCI

Sciatic nerve, unilateral

• Cerebrospinal fluid from cisterna magna

• Serum

SED

(n = 6–9)

TR

(n = 6–9)

4

3 weeks

30 min

16 m/min

Sartini S 2013 [52]

Italy

ECT

Rats

Sprague–Dawley

M

6

150–200

Nerve crush injury

Soleus nerve, unilateral

Soleus muscle, ipsilateral

SED

(n = 5)

TR

(n = 5)

4

Outcome

10 dpi: 7 days

40 dpi: 37 days

30 min, twice per day

5 min on, 5 min off, on periods were 4 min increase from 0–27 m/min and 1 min at 27 m/min

Sheahan TD 2015 [39]

USA

ECT

Mice

C57BL/6 J

M

7–10

21–24.6

SNI

Sciatic nerve, unilateral

Center hindpaw Intraepidermal nerve fiber density, ipsilateral

CG1: SED 2 h/night (n = 7)

IG1: VWR 2 h/night

(n = 8)

8–10

6 days

2 h/night

Voluntary

CG2: SED 12 h/night (n = 5)

IG2: VWR 12 h/night

(n = 7)

8–10

6 days

12 h/night

Voluntary

Sumizono M 2018 [56]

Japan

RCT

Rats

Sprague–Dawley

M

8

274.3 ± 21.2

CCI

Sciatic nerve, unilateral

• Periaqueductal gray

• Lumbar spinal cord dorsal horn segments, ipsilateral

SED

(n = 25)

IG1: TR1 High frequency

(n = 27)

1 or 2

5 weeks

30 min

TR1: 5 day per week 20 m/min

IG2: TR2 Low frequency

(n = 10)

1 or 2

5 weeks

30 min

TR2: 3 day per week 20 m/min

Taguchi S 2015 [48] Japan

ECT

Mice

C57BL/6 J

M

12

NR

PSL

Sciatic nerve, unilateral

Sciatic nerve, ipsilateral

SED

(n = 8)

TR

(n = 8)

2

5 days

60 min

7 m/min

Tsai KL 2017 [47]

Taiwan

ECT

Rats

Sprague–Dawley

M

8–9

285–335

CCI

Sciatic nerve, unilateral

Sciatic nerve, ipsilateral

SED

(n = 6)

IG1: TR0%

(n = 6)

6

3 weeks

30 min

14–16 m/min, 0% incline

IG2: TR8%

(n = 6)

6

3 weeks

30 min

14–16 m/min, 8% incline

Wang Y 2016 [43]

China

RCT

Rabbits

New Zealand white

M

11–12

1780 ± 120

Nerve crush injury

Sciatic nerve, unilateral

Tibia, cortical bone

from the tibial shaft, ipsilateral

SED

(n = 6)

TR

(n = 6)

3

4 weeks

20 min

Day 1–3: 10 m/min,

day 4–6: 15 m/min, 7 days + : 20 m/min

Yamaoka S [22]

Japan

RCT

Rats

Wistar

F

6–8

NR

Spinal nerve ligation

L5, unilateral

Spinal cord dorsal horn, resected Th11, bilateral (ipsilateral data extracted)

SED

(n = 6)

TR

(n = 6)

1

NR

10 min

Increasing: 10 m/min up to 20 m/min

  1. CCI chronic constriction injury, CG control group, dpi days post-injury, ECT experimentally controlled trial, F female, IG intervention group, M male, MET maximum exercise test, NA not applicable, NR not reported, PSL partial sciatic nerve ligation, RCT randomized controlled trial, SE swimming exercise, SED sedentary, SNI spared nerve injury, TR treadmill running, USA United States of America, VWR voluntary wheel running
  2. aCut and repair
  3. bVehicle injection