NLRP3 inflammasome in traumatic brain injury: Its implication in the disease pathophysiology and potential as a therapeutic target

Chakraborty, Rajarshi; Tabassum, Heena; Parvez, Suhel

doi:10.1016/j.lfs.2022.121352

Cited by 18 publications

(19 citation statements)

References 121 publications

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“…It is well documented that TBI leads to extensive damage of neuronal associated with behavioral disturbances [15,32]. In this study, SB332235 was capable of ameliorating the neuronal damage and improved subsequent motor and cognitive de cits at 3 days post-injury.…”

Section: Discussionmentioning

confidence: 53%

“…NLRP3 in ammasome is reported to play an essential role in the in ammatory response following TBI. This in ammasome is composed of an adaptor protein called protein-apoptosis-associated speck-like protein, encompassing a CARD (ASC) and caspase-1 [15]. In the present study, we investigated the impact of SB332235 on the activation of the NLRP3 in ammasome in TBI.…”

Section: Sb332235 Suppresses Cxcr2 Expression and Nlrp3 In Ammasome C...mentioning

confidence: 99%

“…It is well established that the production of proin ammatory factors is associated with the activation of NLRP3 in ammasome proteins in TBI [15]. To investigate whether the repression of NLRP3 by SB332235 could decrease the levels of pro-in ammatory cytokines, we tested the IL-1β, IL-6, IL-18, and TNF-α levels in the peri-lesional cortex.…”

Section: Sb332235 Reduces In Ammatory Factors In Tbimentioning

confidence: 99%

“…Recent efforts have demonstrated that the activation of NOD-, LRR-and pyrin domain-containing protein 3 (NLRP3) in ammasome plays a pivotal role in the regulation of the TBI-induced neuroimmune response [12,13]. TBI activates NLRP3 in ammasome resulting in the elevation of pro-in ammatory cytokine production [14,15]. Moreover, converging evidence reveals that TBI results in NLRP3 in ammasome activation in microglia [12,16,17], which releases several key pro-in ammatory cytokines, such as Interleukin (IL)-1β, IL-6, Tumor Necrosis Factor-alpha (TNF-α) [15].…”

Section: Introductionmentioning

confidence: 99%

“…TBI activates NLRP3 in ammasome resulting in the elevation of pro-in ammatory cytokine production [14,15]. Moreover, converging evidence reveals that TBI results in NLRP3 in ammasome activation in microglia [12,16,17], which releases several key pro-in ammatory cytokines, such as Interleukin (IL)-1β, IL-6, Tumor Necrosis Factor-alpha (TNF-α) [15]. These ndings manifest that the NLRP3-IL-1β signaling pathway plays a prominent role in TBI-induced neuroin ammation.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Neuroprotective Effects of CXCR2 Antagonist SB332235 on Traumatic Brain Injury Through Suppressing NLRP3 Inflammasome

Zhao

Zhou

Gou

et al. 2023

Preprint

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The inflammatory process mediated by nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain comprising 3 (NLRP3) inflammasome plays a predominant role in the neurological dysfunction following traumatic brain injury (TBI). SB332235, a highly selective antagonist of chemokine receptor 2 (CXCR2), has been demonstrated to exhibit anti-inflammatory properties and improve neurological outcomes in the central nervous system. We aimed to determine the neuroprotective effects of SB332235 in the acute phase after TBI in mice and to elucidate its underlying mechanisms. Male C57BL/6J animals were exposed to a controlled cortical impact, then received 4 doses of SB332235, with the first dose administered 30 min after TBI, followed by additional doses at 6, 24, and 30 hours. Neurological defects were assessed by the modified neurological severity score, while the motor function was evaluated using the beam balance and open field tests. Cognitive performance was evaluated using the novel object recognition test. Brain tissues were collected for pathological, Western blot, and immunohistochemical analyses. The results showed that SB332235 significantly ameliorated TBI-induced deficits, including motor and cognitive impairments. Moreover, SB332235 substantially mitigated the augmented expression levels and activation of the NLRP3 inflammasome within the peri-contusional cortex induced by TBI. This was accompanied by the blocking of subsequent production of pro-inflammatory cytokines. Additionally, SB332235 hindered microglial activity induced by TBI. These findings confirmed the neuroprotective effects of SB332235 against TBI, and the involved mechanisms were in part due to the suppression of NLRP3 inflammasome activity. This study suggests that SB332235 may act as an anti-inflammatory agent to improve functional outcomes in brain injury when applied clinically.

show abstract

Section: Discussionmentioning

confidence: 53%

Section: Sb332235 Suppresses Cxcr2 Expression and Nlrp3 In Ammasome C...mentioning

confidence: 99%

Section: Sb332235 Reduces In Ammatory Factors In Tbimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Neuroprotective Effects of CXCR2 Antagonist SB332235 on Traumatic Brain Injury Through Suppressing NLRP3 Inflammasome

Zhao

Zhou

Gou

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Role of NLRP3 inflammasome-mediated neuronal pyroptosis and neuroinflammation in neurodegenerative diseases

Han,

Liu,

Jin

et al. 2023

Inflamm. Res.

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Neuroprotective Effects of CXCR2 Antagonist SB332235 on Traumatic Brain Injury Through Suppressing NLRP3 Inflammasome

Zhao,

Zhou,

Chen

et al. 2023

Neurochem Res

View full text Add to dashboard Cite

The inflammatory process mediated by nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain comprising 3 (NLRP3) inflammasome plays a predominant role in the neurological dysfunction following traumatic brain injury (TBI). SB332235, a highly selective antagonist of chemokine receptor 2 (CXCR2), has been demonstrated to exhibit anti-inflammatory properties and improve neurological outcomes in the central nervous system. We aimed to determine the neuroprotective effects of SB332235 in the acute phase after TBI in mice and to elucidate its underlying mechanisms. Male C57BL/6J animals were exposed to a controlled cortical impact, then received 4 doses of SB332235, with the first dose administered at 30 min after TBI, followed by additional doses at 6, 24, and 30 h. Neurological defects were assessed by the modified neurological severity score, while the motor function was evaluated using the beam balance and open field tests. Cognitive performance was evaluated using the novel object recognition test. Brain tissues were collected for pathological, Western blot, and immunohistochemical analyses. The results showed that SB332235 significantly ameliorated TBI-induced deficits, including motor and cognitive impairments. SB332235 administration suppressed expression of both CXCL1 and CXCR2 in TBI. Moreover, SB332235 substantially mitigated the augmented expression levels and activation of the NLRP3 inflammasome within the peri-contusional cortex induced by TBI. This was accompanied by the blocking of subsequent production of pro-inflammatory cytokines. Additionally, SB332235 hindered microglial activity induced by TBI. These findings confirmed the neuroprotective effects of SB332235 against TBI, and the involved mechanisms were in part due to the suppression of NLRP3 inflammasome activity. This study suggests that SB332235 may act as an anti-inflammatory agent to improve functional outcomes in brain injury when applied clinically.

show abstract

NLRP3 inflammasome in traumatic brain injury: Its implication in the disease pathophysiology and potential as a therapeutic target

Cited by 18 publications

References 121 publications

Neuroprotective Effects of CXCR2 Antagonist SB332235 on Traumatic Brain Injury Through Suppressing NLRP3 Inflammasome

Neuroprotective Effects of CXCR2 Antagonist SB332235 on Traumatic Brain Injury Through Suppressing NLRP3 Inflammasome

Role of NLRP3 inflammasome-mediated neuronal pyroptosis and neuroinflammation in neurodegenerative diseases

Neuroprotective Effects of CXCR2 Antagonist SB332235 on Traumatic Brain Injury Through Suppressing NLRP3 Inflammasome

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