Projects and Grants per year
Grants and Contracts Details
Description
Our long term goals are to develop effective pharmacological and rehabilitative treatment strategies that
promote adaptive reorganization of brain-injured circuits to mitigate neurological dysfunction (morbidity) after
diffuse traumatic brain injury (TBI). To achieve these goals, we will exploit a novel, reproducible, late-onset
neurological deficit that we have observed in the diffuse brain-injured rat, analogous to agitation in brain injury
survivors. In contrast to the soothing and pacifying nature of facial whisker stimulation in uninjured rats, brain-
injured rats react to whisker stimulation by cowering, freezing and guarding the mystacial pads. This aberrant
behavior is concomitant with axonal damage, neuronal atrophy, persistent inflammation and neuroplasticity,
such that whisker stimulation activates brain regions outside the conventional somatosensory whisker circuit.
The current proposal tests the hypothesis that diffuse brain injury-induced inflammation drives the
maladaptive structural plasticity responsible for aberrant behavioral responses to whisker stimulation.
The model system afforded by the brain-injured somatosensory whisker circuit provides a reductionistic
approach to the complexity of diffuse TBI, to address pathological and reparative mechanisms associated with
post-traumatic morbidity. This circuit in diffuse brain-injured adult male rats will be evaluated for (Aim 1)
aberrant behaviors elicited by whisker stimulation, (Aim 2) chronic neuropathology, neuronal activation and
circuit reorganization, and (Aim 3) neuroinflammation-driven neuroplastic responses that contribute to circuit
reorganization and morbidity. An anti-inflammatory therapeutic regimen may provide a clinically relevant
intervention to prevent circuit rewiring and the onset of morbidity. The innovative combination of behavioral,
anatomical, functional and therapeutic approaches directed at the brain-injured somatosensory whisker circuit
addresses the underlying mechanisms associated with unregulated structural plasticity in the injured brain.
Uncovering these processes can direct treatments to mitigate the onset, reduce the duration and/or promote
the resolution of neurological dysfunction. Results from this circuit can ultimately be expanded to other circuits
in rodents and then man to improve quality of life for millions of TBI survivors and potentially others suffering
from progressive neurodegenerative diseases.
Status | Finished |
---|---|
Effective start/end date | 2/1/10 → 5/31/12 |
Funding
- National Institute of Neurological Disorders & Stroke: $403,399.00
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Projects
- 1 Finished
-
Research Supplements to Promote Diversity in Health-Related Research
Lifshitz, J. (PI) & Rowe, R. (CoI)
7/1/10 → 5/31/12
Project: Research project