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Table 1 Prevalence of pre-clinical stroke guidelines in stroke studies using NOX knockout mice

From: The 1027th target candidate in stroke: Will NADPH oxidase hold up?

NOX isoform

Parameters analysed

Transient MCAO model

Permanent model

Age/ Weight

Gender

Litter-mates

Power

Operator- blinded

>24 h

Outcome

Reference

NOX1

mortality, infarct, edema, functional outcome

30 min/23.5 h

✗

11-17 wk

m

✓

n.s.

✓

✗

cortical but not total infarct ↑ in NOX1 KOs

[10]

infarct, BBB, functional outcome, apoptosis, NOX1 mRNA + protein levels

1/23 h and 2/22 h

pMCAO

n.s.

m

✓

n.s.

n.s.

✗

NOX1 KOs protected

[11]

mortality, infarct, edema/BBB, functional outcome, hemorraghe, NOX1 mRNA +  protein levels, ROS + RNS, apoptosis.

1/23 h and 1 h/6d

pMCAO, cortical PT

6-8 wk

m

✗

93%

✓

6 d

no significant difference

[12]

NOX2

infarct, ROS, neutrophils

2/22 h

✗

8-10 wk

m

✓

n.s.

n.s.

✗

NOX2 KOs protected but not with WT bone marrow implant

[13]

infarct, ROS

25 min/3d

✗

6 wk

m

✓

n.s.

n.s.

3 d

NOX2 KOs protected

[14]

infarct, BBB

2/22 h

✗

7-9 wk

m

✗

n.s.

n.s.

✗

NOX2 KOs protected

[15]

infarct, functional outcome, oxidative stress, cell death, neutrophils, inflammation

75 min/22.75 h and 75 min/3d

✗

12-16 wk

m

✗

n.s.

n.s.

3 d

NOX2 KOs protected

[16]

mortality, infarct, functional outcome, ROS

30 min/23.5 h

✗

6-8 wk

m

✗

n.s.

✓

✗

NOX2 KOs protected

[17]

infarct, edema, functional outcome, NOX2 protein levels, ROS.

30 min/23.5 h and 30 min/3d

pMCAO

6-8 wk

m + f

✗

n.s.

✓

3 d

only male NOX2 KOs protected

[18]

mortality, infarct, edema/BBB, functional outcome, hemorraghe, mRNA + protein levels, ROS + RNS, apoptosis.

1/23 h and 1 h/6d

pMCAO, cortical PT

6-8 wk and 18–20 wk (unpublished)

m

✗

93%

✓

6 d

no significant difference

[12]

infarct, RNS, cell death, inflammatory markers

75 min/24 h and 75 min/72 h

✗

12-16 wk

m

✗

n.s.

n.s.

3 d

NOX2 KOs protected

[19]

infarct, BBB, functional outcome, hemorraghe, ROS

2/22 h

✗

25-30 g

m

✗

n.s.

n.s.

✗

NOX2 KOs protected

[20]

mortality, infarct, edema, functional outcome, NOX2 protein levels, ROS + RNS, NO function.

30 min/23.5 h

✗

8-12 wk

m

✗

n.s.

✓

✗

NOX2 KOs protected

[21]

NOX4

mortality, infarct, edema/BBB, functional outcome, hemorraghe, mRNA + protein levels, ROS + RNS, apoptosis.

1/23 h and 1 h/6d

pMCAO, cortical PT

6-8 wk and 18–20 wk

m + f

✗

93%

✓

6 d

NOX4 KOs protected

[12]

  1. Published studies evaluating the role of NADPH oxidases in stroke by means of KO mice were assessed for their translatability. Parameters that should be investigated when performing a stroke study are, amongst others, the use of aged mice of both genders, and wildtype littermates as negative controls. In addition to transient models, a permanent model should be added, and animals should be assessed for longer time periods than 24 h. Finally, power calculations should be reported. All of the above cited studies used temperature control and monitored cerebral blood flow. Unfortunately, none of these studies included animals that present co-morbidities.
  2. BBB: blood brain barrier leakage; d: days; f: female; h: hours; KO: knock out; m: male; min: minutes; n.s.: not specified; pMCAO: permanent middle cerebral artery occlusion; PT: photothrombosis; ROS: reactive oxygen species; RNS: reactive nitrogen species; wk: weeks.