Table 1 Inflammasome expression/activity from clinical and preclinical TBI studies along with specific and non-specific NLRP3 inhibitors used in preclinical TBI studies

Adults with moderate and severe TBI

CSF

Upregulated NLRP1, ASC

and caspase-1 proteins.

[41]

Adults with moderate and severe TBI

CSF and serum

Elevated caspase-1 levels in

serum on day 2 and 3 post TBI

[43]

Adults with severe TBI

CSF

Upregulated NLRP1, ASC and

caspase-1 proteins.

[42]

Children with severe TBI

CSF

Increased NLRP3 levels at 0–24, 25–48,

49–72, and > 72 h post-TBI

[44]

Adults with severe TBI

Resected cortex

Upregulation of NLRP3, caspase-1,

IL-1β, and IL-18 proteins

[47]

Preclinical studies - TBI

Inhibitor

Model, species

Effect on inflammasomes

Outcomes

Reference

BAY 11-7082

(20 mg/kg IP)

Once daily for 4 D.P.T

CCI, rats

Decreased protein levels of NLRP3

and caspase-1 in brain at 7 D.P.T.

Improved cognitive function and neuron viability at 7 D.P.T.

[50]

Anti ASC antibodies (20 µg/kg ICV) immediately P.T.

FPI, rats

Decreased protein levels of caspase-1,

IL-1β and NLRP1 at 24 H. P.T.

Reduced contusion volume at 3 D.P.T.

[51]

MCC950

(50 mg/kg IP)

1- and 3-hours P.T.

CCI, mice

Decreased brain protein expression of NLRP3

ASC caspase-1and IL-1β at 24 H. P.T.

Decreased cerebral oedema and improved

neurological function at 24 and 72 H P.T.

[52]

JC124

(100 mg/kg IP)

0.5, 6, 24 and 30 H.P.T.

CCI, rats

Decreased protein expression of NLRP3,

ASC and caspase-1 in injured brain at 2 D.P.T.

Prevented neurodegeneration and

decreased lesion volume at 2 D.P.T.

[53]

Mangiferin

(100 mg/kg IP)

20 min P.T.

Blast-injury, rats

Decreased mRNA and protein levels of NLRP3 and

caspase-1 p20 in brain at 12 and 24 H P.T.

Ameliorated cerebral oedema and oxidative stress at 12 and 24 H.P.T.

[46]

Omega-3 fatty acids (100 mg/kg oral gavage)

twice a week for 6 weeks before TBI

CCI, rats

Decreased protein expression of NLRP3,

caspase-1 and IL-1β in the brain at

8 H. P.T.

Decreased oedema and cortical lesion volume at 3 D

and improved motor and cognitive performance at 11–15-D. P.T.

[47]

Apocynin

(5 mg/kg IP) Every 24 h for 4 D.P.T.

CCI, rats

Decreased protein expression of NLRP3, ASC,

caspase-1 and IL-1β in the brain at 4 D. P.T.

Decreased lesion size and neuronal death in injured cortex at 4 D. P.T.

[54]

Oridonin

(10 mg/kg IP)

30 min P.T.

Weight Drop, mice

Decreased brain mRNA and protein levels of NLRP3,

ASC and caspase-1 at 24 H. P.T.

Decreased oedema and cortical lesion volume at 24 H P.T,

improved sensory motor function (2,4,7,14 D.P.T)

[55]

Dexmedetomidine

(25 µg/kg IP for 3 D P.T)

CCI, mice

Decreased protein expression of NLRP3 caspase-1

and IL-1β in brain at 3 D.P.T.

Attenuated BBB disruption and neurological deficit at 3 D.P.T.

[50, 56]

Artesunate

(30 mg/kg IP)

1 H.P.T.

CCI, mice

Decreased protein expression of NLRP3, ASC

and caspase-1 in brain at 24 H. P.T.

Decreased lesion volume, inhibited apoptosis,

and increased neurotrophic factors at 24 H. P.T.

[57]

Propofol

(50 mg/kg IP)

1 H.P.T.

Blast injury, rats

Decreased brain mRNA and protein levels of NLRP3

and caspase-1 p20 at 12 H and 24 H P.T.

Attenuated cortical damage and oxidative

stress at 12 H and 24 H P.T.

[58]

Pioglitazone

(20 mg/kg IP)

Daily till sacrifice (1,3,7,14 days)

Weight drop, mice

Decreased brain protein expression of NLRP3 on

(3,7 D) caspase-1(1,3,7,14 D) and IL-1β 14 D. P. T

Reduced cerebral oedema and microglial activation at 3 D. P.T.

[59]

Telmisartan

(10 mg/kg PO) 1 h before TBI

Cryogenic injury, mice

Decreased brain mRNA and protein levels of NLRP3,

ASC and caspase-1 at 24 H P.T.

Reduced BBB disruption, decreased lesion volume,

and improved neurological function at 24 H P.T.

[60]

hMSC-EVs

Intra nasal, 90 min P.T.

CCI, mice

Decreased protein expression of NLRP3, ASC,

caspase-1 and IL-1β in brain at 84 D.P.T.

Improved long term mood and cognitive impairment at 63–84 D.P.T.

[48]

ADSCs-Exo

(IV, 24 h before TBI)

Weight drop, rats

Decreased protein expression of NLRP3

and caspase-1 at 24 H P.T.

Improved sensorimotor function at 7–35 D. P. T

[49]