Funding Agency:

The Pittsburgh Foundations

Total Project Period:

10/01/07 - 09/30/08

Total Project Award:

$20,000

Principal Investigator:

P. David Adelson, MD

Co-Investigators:

J. Patrick Card, Wendy Fellows, MA, PhD

Project Summary:

Traumatic brain injury (TBI) remains a leading cause of death and disability in children. There is increasing evidence that moderate hypothermia (HYPO) following pediatric TBI may be efficacious.

For this proposal, we postulate the HYPO Is beneficial following experimental pediatric TBI by Improving synaptic connectivity in treated Injured animals. We further postulate that the effects on synaptic connectivity will vary at different maturational ages due to differences in the sensitivity of the developing brain to injury, response to treatment, and recovery as measured by increased cortical and hippocampal dendritic arborization, and synaptic circuitry and improvements in post-injury molecular markers of synaptic connectivity.

Our hypothesis and specific aims are:

Hypothesis: Treatment with HYPO applied in the acute period following experimental CCI In the Immature (PND 7 and 17) rat will increase the expression of histologic and molecular markers of dendritic arborization, spine formation, and synaptogenesis and in the generation of functional synapses.

Specific Aim 1A: To determine whether HYPO after CCI In immature rates will increase synaptic connectivity and dendritic spine formation In cortex (CTX) and hippocampus (HC).

Specific Aim 1B: To determine whether HYPO after CCI In immature rate will increase expression of molecular markers of synaptic connectivity and functioning CTX and HC.