Selective NLRP3 inflammasome inhibitor reduces neuroinflammation and improves long-term neurological outcomes in a murine model of traumatic brain injury

Abstract Background Cognitive impairment in the late stage of traumatic brain injury (TBI) is associated with the NOD-, LRR and pyrin domain-containing protein 3 (NLRP3) inflammasome, which plays an important role in neuroinflammation. Although classical inflammatory pathways have been well-documented in the late stage of TBI (4–8 weeks post-injury), the mechanism by which the NLRP3 inflammasome impairs cognition is still unclear. Methods Mice lacking the gene encoding for NLRP3 (NLRP3-knockout mice) and their wild-type littermates were used in a controlled cortical impact model of TBI. Levels of NLRP3 inflammasome and inflammatory factors such as IL-1β and HMGB1 were detected in post-injury hippocampal tissue, as well as long-term potentiation. Behaviors were assessed by T-maze test, novel object recognition, and nesting tests. Glycyrrhizin was used to antagonize HMGB1. Calcium imaging were performed on primary neuronal cultures. Results By using the NLRP3-knockout TBI model, we found that the continuous activation of the NLRP3 inflammasome and high mobility group box 1 (HMGB1) release were closely related to cognitive impairment. We also found that inhibition of HMGB1 improved LTP reduction and cognitive function by increasing the phosphorylation level of the NMDAR1 subunit at serine 896 while reducing NLRP3 inflammasome activation. Conclusion NLRP3 inflammasome damages memory in the late stage of TBI primarily through HMGB1 upregulation and provides an explanation for the long-term progression of cognitive dysfunction.

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Traumatic Brain Injury: A Trauma Surgeon's Perspective

Perspectives on Neurophysiology and Neurogenic Speech and Language Disorders ◽

10.1044/nnsld22.3.82 ◽

2012 ◽

Vol 22 (3) ◽

pp. 82-89

Author(s):

Oscar D. Guillamondegui

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Multidisciplinary Approach ◽

Trauma Team ◽

The United States ◽

Long Term Outcomes ◽

Term Care ◽

Injured Brain ◽

The Moment

Traumatic brain injury (TBI) is a serious epidemic in the United States. It affects patients of all ages, race, and socioeconomic status (SES). The current care of these patients typically manifests after sequelae have been identified after discharge from the hospital, long after the inciting event. The purpose of this article is to introduce the concept of identification and management of the TBI patient from the moment of injury through long-term care as a multidisciplinary approach. By promoting an awareness of the issues that develop around the acutely injured brain and linking them to long-term outcomes, the trauma team can initiate care early to alter the effect on the patient, family, and community. Hopefully, by describing the care afforded at a trauma center and by a multidisciplinary team, we can bring a better understanding to the armamentarium of methods utilized to treat the difficult population of TBI patients.

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Prosodic Impairment Associated With Traumatic Brain Injury

Perspectives on Neurophysiology and Neurogenic Speech and Language Disorders ◽

10.1044/nnsld19.3.97 ◽

2009 ◽

Vol 19 (3) ◽

pp. 97-102

Author(s):

Billy Irwin

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Detailed Analysis ◽

Acoustic Characteristics ◽

Individual Variations

Abstract Purpose: This article discusses impaired prosody production subsequent to traumatic brain injury (TBI). Prosody may affect naturalness and intelligibility of speech significantly, often for the long term, and TBI may result in a variety of impairments. Method: Intonation, rate, and stress production are discussed in terms of the perceptual, physiological, and acoustic characteristics associated with TBI. Results and Conclusions: All aspects of prosodic production are susceptible to the effects of damage resulting from TBI. There are commonly associated prosodic impairments; however, individual variations in specific aspects of prosody require detailed analysis.

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