Brain Injury and Neuroprotection Research: Anesthesiology

Brain Injury and Neuroprotection Research

Neuron-specific Conditional
Expression of a Mitochondrially
Targeted Fluorescent Protein
In Mice

Mitochondrially-targeted eYFP(green) is shown in CA1
pyramidal cells whose cell bodies were labeled with
anti-NeuN antibbodies (red).

Mission

Acute brain injury caused by stroke, cardiac arrest, transient hypoxia and head trauma affects over 1 million people each year in the US alone. Our mission is to improve the survival and quality of life for brain injury victims. Our approach includes the use of both basic and translational research directed at understanding the molecular mechanisms of neural cell death. We also use tissue and fluid samples obtained from traumatic brain injury patients to validate the mechanisms elucidated from our animal models and to identify accurate biomarkers
of acute neurodegeneration.

Focus of study

Relationships between excitotoxicity, cellular calcium overload, metabolic failure, and oxidative stress with emphasis on the role that mitochondrial dysfunction plays in both necrotic and apoptotic cell death.

Normoxic Resuscitation After Cardiac Arrest Protects Against Hippocampal Oxidative Stress, Metabolic Dysfunction, and Neuronal Death

Following 10 min of v-fib cardiac arrest, chloralose-anesthetized animals were resuscitated on either 100% O2 (Hyperoxic) or 21% O2 (Normoxic). After 1 hr, ventilatory adjustments maintained normal PaO2 in both groups. After 2 hr, the brains were perfusion-fixed and processed for GFAP (red) and nitrotyrosine (green) immunostaining. The dramatic decrease in nitrotyrosine immunostaining in the hippocampus of the Normoxic compared to the Hyperoxic animal indicates protection against early, postischemic oxidative stress.

Research Topics

Brain mitochondrial physiology and bioenergetics
Oxidative stress
Cerebral energy metabolism
Necrotic and apoptotic neural cell death
Brain inflammation
Translational research utilizing animal models of cerebral ischemia, traumatic brain injury, neonatal asphyxia
Development of clinically feasible neuroprotective interventions

Resources

Small and large animal surgical facilities
Fluorescence live cell imaging workstation with environmental control
Histology workstation with advanced stereology
Anoxia chamber
Multi-incubator cell culture system with independent oxygen controls

Physiologic Progesterone Reduces Mitochondrial Dysfunction And Hippocampal Cell Loss After Traumatic Brain Injury In Female Rats

Representative photomicrographs at high-powered magnification of the CA1 subfield of the hippocampus stained for NeuN from ipsilateral hemispheres in blank treated (A,B) and low range progesterone treated (C) at 7 days after TBI. In Figure 3A, a blank-implanted rat shows a marked reduction in total hippocampal neurons seen with NeuN labeling, with many abnormally stained neurons (arrow heads in insert) and few normally stained neurons (arrow in insert) amongst remaining cells. In Figure 3B, a blank-implanted rat shows a normal cell density, but an abundance of abnormally stained neurons (arrow heads in insert). Figure 3C shows a progesterone treated rat with preservation of normal cell numbers and a predominance of normal NeuN staining (arrows in insert).