Importance of Control Groups for Evaluating Long-Term Behavioral and Cognitive Outcomes of Controlled Cortical Impact in Immature Rats.

Therapies are limited for pediatric traumatic brain injury (TBI), especially for the very young who can experience long-term consequences to learning, memory, and social behavior. Animal models of pediatric TBI have yielded mechanistic insights, but demonstration of clinically relevant long-term behavioral and/or cognitive deficits has been challenging. We characterized short- and long-term outcomes in a controlled cortical impact (CCI) model of pediatric TBI using a panel of tests between 2 weeks and ∼4 months after injury.

Resuscitation with macromolecular superoxide dismutase/catalase mimetic polynitroxylated PEGylated hemoglobin offers neuroprotection in guinea pigs after traumatic brain injury combined with hemorrhage shock.

Background: Polynitroxylated PEGylated hemoglobin (PNPH, aka SanFlow) possesses superoxide dismutase/catalase mimetic activities that may directly protect the brain from oxidative stress. Stabilization of PNPH with bound carbon monoxide prevents methemoglobin formation during storage and permits it to serve as a carbon monoxide donor. We determined whether small volume transfusion of hyperoncotic PNPH is neuroprotective in a polytrauma model of traumatic brain injury (TBI) plus hemorrhagic shock.

Pediatric Traumatic Brain Injury Causes Long-Term Deficits in Adult Hippocampal Neurogenesis and Cognition.

Young children who have sustained severe traumatic brain injury (TBI) can suffer from debilitating neurocognitive deficits. Impairment of adult hippocampal neurogenesis is associated with cognitive deficits and depression. Very few studies have investigated the adult hippocampal neurogenesis after pediatric TBI.

An Inhibitor of the Mitochondrial Permeability Transition Pore Lacks Therapeutic Efficacy Following Neonatal Hypoxia Ischemia in Mice.

Neonatal hypoxic ischemic (HI) brain injury causes lifelong neurologic disability. Therapeutic hypothermia (TH) is the only approved therapy that partially mitigates mortality and morbidity. Therapies specifically targeting HI-induced brain cell death are currently lacking.

Traumatic Injury Leads to Inflammation and Altered Tryptophan Metabolism in the Juvenile Rabbit Brain.

Neuroinflammation after traumatic brain injury (TBI) contributes to widespread cell death and tissue loss. Here, we evaluated sequential inflammatory response in the brain, as well as inflammation-induced changes in brain tryptophan metabolism over time, in a rabbit pediatric TBI model. On post-natal days 5-7 (P5-P7), New Zealand white rabbit littermates were randomized into three groups: naïve (no injury), sham (craniotomy alone), and TBI (controlled cortical impact).

A New Rabbit Model of Pediatric Traumatic Brain Injury.

Traumatic brain injury (TBI) is a common cause of disability in childhood, resulting in numerous physical, behavioral, and cognitive sequelae, which can influence development through the lifespan. The mechanisms by which TBI influences normal development and maturation remain largely unknown. Pediatric rodent models of TBI often do not demonstrate the spectrum of motor and cognitive deficits seen in patients.

Progesterone protects mitochondrial function in a rat model of pediatric traumatic brain injury.

Progesterone has been studied extensively in preclinical models of adult traumatic brain injury (TBI), and has advanced to clinical trials in adults with TBI. However, there are very few preclinical studies in pediatric TBI models investigating progesterone for neuroprotection. Immature male and female rats (postnatal day, PND 17-21) underwent controlled cortical impact (CCI) to the left parietal cortex.

Evidence for impaired plasticity after traumatic brain injury in the developing brain.

The robustness of plasticity mechanisms during brain development is essential for synaptic formation and has a beneficial outcome after sensory deprivation. However, the role of plasticity in recovery after acute brain injury in children has not been well defined. Traumatic brain injury (TBI) is the leading cause of death and disability among children, and long-term disability from pediatric TBI can be particularly devastating.

Cerebral glucose metabolism in an immature rat model of pediatric traumatic brain injury.

Altered cerebral metabolism and mitochondrial function have been identified in experimental and clinical studies of pediatric traumatic brain injury (TBI). Metabolic changes detected using (1)H (proton) magnetic resonance spectroscopy correlate with long-term outcomes in children after severe TBI. We previously identified early (4-h) and sustained (24-h and 7-day) abnormalities in brain metabolites after controlled cortical impact (CCI) in immature rats.

Cyclosporin A preserves mitochondrial function after traumatic brain injury in the immature rat and piglet.

Cyclosporin A (CsA) has been shown to be neuroprotective in mature animal models of traumatic brain injury (TBI), but its effects on immature animal models of TBI are unknown. In mature animal models, CsA inhibits the opening of the mitochondrial permeability transition pore (MPTP), thereby maintaining mitochondrial homeostasis following injury by inhibiting calcium influx and preserving mitochondrial membrane potential. The aim of the present study was to evaluate CsA's ability to preserve mitochondrial bioenergetic function following TBI (as measured by mitochondrial respiration and cerebral microdialysis), in two immature models (focal and diffuse), and in two different species (rat and piglet).

Early and sustained alterations in cerebral metabolism after traumatic brain injury in immature rats.

Although studies have shown alterations in cerebral metabolism after traumatic brain injury (TBI), clinical data in the developing brain is limited. We hypothesized that post-traumatic metabolic changes occur early (<24 h) and persist for up to 1 week. Immature rats underwent TBI to the left parietal cortex.

Mitochondrial dysfunction early after traumatic brain injury in immature rats.

Mitochondria play central roles in acute brain injury; however, little is known about mitochondrial function following traumatic brain injury (TBI) to the immature brain. We hypothesized that TBI would cause mitochondrial dysfunction early (<4 h) after injury. Immature rats underwent controlled cortical impact (CCI) or sham injury to the left cortex, and mitochondria were isolated from both hemispheres at 1 and 4 h after TBI.

Physiologic progesterone reduces mitochondrial dysfunction and hippocampal cell loss after traumatic brain injury in female rats.

Growing literature suggests important sex-based differences in outcome following traumatic brain injury (TBI) in animals and humans. Progesterone has emerged as a key hormone involved in many potential neuroprotective pathways after acute brain injury and may be responsible for some of these differences. Many studies have utilized supraphysiologic levels of post-traumatic progesterone to reverse pathologic processes after TBI, but few studies have focused on the role of endogenous physiologic levels of progesterone in neuroprotection.

Immunolocalization of Bex protein in the mouse brain and olfactory system.

Bex proteins are expressed from a family of "brain expressed X-linked genes" that are closely linked on the X-chromosome. Bex1 and 2 have been characterized as interacting partners of the olfactory marker protein (OMP). Here we report the distribution of Bex1 and Bex2 mRNAs in several brain regions and the development and characterization of an antibody to mouse Bex1 protein that cross-reacts with Bex2 (but not Bex3), and its use to determine the cellular distribution of Bex proteins in the murine brain.