Systemic treatment with ubiquitin carboxy terminal hydrolase L1 TAT protein ameliorates axonal injury and reduces functional deficits after traumatic brain injury in mice.

Traumatic brain injury (TBI) is often associated with axonal injury that leads to significant motor and cognitive deficits. Ubiquitin carboxy terminal hydrolase L1 (UCHL1) is highly expressed in neurons and loss of its activity plays an important role in the pathogenesis of TBI. Fusion protein was constructed containing wild type (WT) UCHL1 and the HIV trans-activator of transcription capsid protein transduction domain (TAT-UCHL1) that facilitates transport of the protein into neurons after systemic administration.

Localization of Multi-Lamellar Vesicle Nanoparticles to Injured Brain Tissue in a Controlled Cortical Impact Injury Model of Traumatic Brain Injury in Rodents.

Severe traumatic brain injury (TBI), such as that suffered by patients with cerebral contusion, is a major cause of death and disability in young persons. Effective therapeutics to treat or mitigate the effects of severe TBI are lacking, in part because drug delivery to the injured brain remains a challenge. Promising therapeutics targeting secondary injury mechanisms may have poor pharmacokinetics/pharmacodynamics, unwanted side effects, or high hydrophobicity.

Mutation of a Ubiquitin Carboxy Terminal Hydrolase L1 Lipid Binding Site Alleviates Cell Death, Axonal Injury, and Behavioral Deficits After Traumatic Brain Injury in Mice.

Ubiquitin carboxy terminal hydrolase L1 (UCHL1) is a protein highly expressed in neurons that may play important roles in the ubiquitin proteasome pathway (UPP) in neurons, axonal integrity, and motor function after traumatic brain injury (TBI). Binding of reactive lipid species to cysteine 152 of UCHL1 results in unfolding, aggregation, and inactivation of the enzyme. To test the role of this mechanism in TBI, mice bearing a cysteine to alanine mutation at site 152 (C152A mice) that renders UCHL1 resistant to inactivation by reactive lipids were subjected to the controlled cortical impact model (CCI) of TBI and compared to wild type (WT) controls.

Choice of Whole Blood versus Lactated Ringer's Resuscitation Modifies the Relationship between Blood Pressure Target and Functional Outcome after Traumatic Brain Injury plus Hemorrhagic Shock in Mice.

Civilian traumatic brain injury (TBI) guidelines recommend resuscitation of patients with hypotensive TBI with crystalloids. Increasing evidence, however, suggests that whole blood (WB) resuscitation may improve physiological and survival outcomes at lower resuscitation volumes, and potentially at a lower mean arterial blood pressure (MAP), than crystalloid after TBI and hemorrhagic shock (HS). The objective of this study was to assess whether WB resuscitation with two different MAP targets improved behavioral and histological outcomes compared with lactated Ringer's (LR) in a mouse model of TBI+HS.

A combined therapeutic regimen of buspirone and environmental enrichment is more efficacious than either alone in enhancing spatial learning in brain-injured pediatric rats.

Buspirone, a 5-HT1A receptor agonist, and environmental enrichment (EE) enhance cognition and reduce histopathology after traumatic brain injury (TBI) in adult rats, but have not been fully evaluated after pediatric TBI, which is the leading cause of death in children. Hence, the aims of this study were to assess the efficacy of buspirone alone (Experiment 1) and in combination with EE (Experiment 2) in TBI postnatal day-17 male rats. The hypothesis was that both therapies would confer cognitive and histological benefits when provided singly, but their combination would be more efficacious.