NLRP3 inflammasome and TBI

Project: Research project

Description

DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) is a leading cause of mortality and long-term disability worldwide. Over 1.7 million Americans suffer a TBI annually and up to 2% of the population currently lives with the long-term neurological consequences of a previous TBI, placing a $76.5 billion annual economic burden on society. Preventative measures reduce injury incidence and/or severity, yet one-third of hospitalized TBI patients die from injuries that are secondary to the initial trauma. Cerebral edema is a life-threatening neurological complication that promotes elevated ICP and leads to clinical deterioration in the hours and days after a TBI. Unfortunately, neurosurgical approaches to control elevated ICP are limited and efficacious medical therapies to control cerebral edema are lacking. A critical barrier
to improving patient prognoses remains a lack of clinically effective treatment options after TBI. The objective of this proposal is to implicate NLRP3 as a functional mediator of neurovascular injury after TBI. Specific Aim 1 will test the hypothesis that P2X7 promotes NLRP3 inflammasome activation after TBI. Specific Aim 2 will test the hypothesis that inhibition of the NLRP3 inflammasome attenuates neurological injury after TBI. Expected outcomes of the proposed research include: (1) identification of P2X7 as a key mediator of NLRP3 inflammasome formation following TBI, and (2) demonstration that NLRP3 promotes cerebral edema and worsens neurological outcomes after TBI. These studies may have far-reaching translational implications as the identification of NLRP3 as a key mediator of secondary injury will provide a novel target for therapeutic intervention. These studies also will provide a mechanism of action whereby two-clinically useful therapeutics control post-traumatic edema, providing rationale for rapid clinical translational of these findings after TBI. !
StatusFinished
Effective start/end date6/1/135/30/16

Funding

  • National Institutes of Health: $75,000.00
  • National Institutes of Health: $74,250.00

Fingerprint

Inflammasomes
Brain Edema
Wounds and Injuries
Traumatic Brain Injury
Therapeutics
Edema

ASJC

  • Medicine(all)
  • Neuroscience(all)