What does this research mean for the field?

Pharmacological or genetic inhibition of microglial hexokinase-2 (HK2) attenuates inflammasome activation, limits post-traumatic inflammation, and improves functional motor recovery following severe traumatic brain injury. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To determine the role of hexokinase-2 in post-traumatic microglial activation and evaluate whether pharmacological or genetic inhibition of this metabolic enzyme improves functional recovery after traumatic brain injury.

August 30, 2026Journal of NeuroinflammationOpen Access

Therapeutic targeting of microglial hexokinase-2 attenuates inflammasome activation and improves functional recovery after traumatic brain injury

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Authors

CMClaudia Mera-Reina JCJuan F. Codocedo PFPaul B Fallen

Discussion

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Implication

Preclinical study demonstrates that inhibiting microglial hexokinase-2 reduces inflammasome activation and improves motor recovery in mice, highlighting a metabolic therapy for brain trauma.

Key Points

To determine the role of hexokinase-2 in post-traumatic microglial activation and evaluate whether pharmacological or genetic inhibition of this metabolic enzyme improves functional recovery after traumatic brain injury.
Measured cortical hexokinase-2 (HK2) expression at 3, 7, and 15 days following severe controlled cortical impact (CCI) in mice.
Treated mice with the HK2 inhibitor lonidamine (50 mg/kg intraperitoneally daily for 7 days, starting 24 hours post-injury) or evaluated microglial-specific HK2-haplodeficient mice.
Assessed in vitro microglial metabolic flux, NF-κB signaling, and phagocytosis, alongside in vivo motor performance (rotarod) and inflammasome activation.
Cortical HK2 mRNA increased by day 3 and remained elevated through day 15 post-CCI, with prominent protein expression detected in IBA1-positive microglia.
Lonidamine restrained acute glycolysis, lowered total ATP production, and suppressed NF-κB reporter activity in vitro without impairing dead-cell phagocytosis.
Both pharmacological lonidamine treatment and genetic reduction of microglial HK2 significantly improved rotarod motor performance and reduced inflammasome-associated gene expression and ASC accumulation.

Cite This Study

Mera-Reina et al. (2026) studied this question.

synapsesocial.com/papers/6a93f0a36c1a8fb52e79cf68 https://doi.org/10.1186/s12974-026-04014-8

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August 30, 2026Journal of NeuroinflammationOpen Access

Therapeutic targeting of microglial hexokinase-2 attenuates inflammasome activation and improves functional recovery after traumatic brain injury

View Full Paper

Ask AI

Bookmark

Authors

CMClaudia Mera-Reina JCJuan F. Codocedo PFPaul B Fallen

Discussion

Member takes

Implication

Preclinical study demonstrates that inhibiting microglial hexokinase-2 reduces inflammasome activation and improves motor recovery in mice, highlighting a metabolic therapy for brain trauma.

Key Points

To determine the role of hexokinase-2 in post-traumatic microglial activation and evaluate whether pharmacological or genetic inhibition of this metabolic enzyme improves functional recovery after traumatic brain injury.
Measured cortical hexokinase-2 (HK2) expression at 3, 7, and 15 days following severe controlled cortical impact (CCI) in mice.
Treated mice with the HK2 inhibitor lonidamine (50 mg/kg intraperitoneally daily for 7 days, starting 24 hours post-injury) or evaluated microglial-specific HK2-haplodeficient mice.
Assessed in vitro microglial metabolic flux, NF-κB signaling, and phagocytosis, alongside in vivo motor performance (rotarod) and inflammasome activation.
Cortical HK2 mRNA increased by day 3 and remained elevated through day 15 post-CCI, with prominent protein expression detected in IBA1-positive microglia.
Lonidamine restrained acute glycolysis, lowered total ATP production, and suppressed NF-κB reporter activity in vitro without impairing dead-cell phagocytosis.
Both pharmacological lonidamine treatment and genetic reduction of microglial HK2 significantly improved rotarod motor performance and reduced inflammasome-associated gene expression and ASC accumulation.

Cite This Study

Mera-Reina et al. (2026) studied this question.

synapsesocial.com/papers/6a93f0a36c1a8fb52e79cf68 https://doi.org/10.1186/s12974-026-04014-8

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