The long-term goal ofthe project is to identify common and distinct features of behavioral changes after three types of brain injury (subarachnoid hemorhage, intracerebral hemorhage, and traumatic brain injury) and the response to therapeutic interventions (osteopontin, anti-PDGF, Cav-AP) that protect the blood brain barrier and reduce brain swelling. The Behavioral Core will complement the scientific role ofthe project by implementing methods that can directly compare and contrast injury phenotype and treatment outcomes on a large number of subjects. The Behavioral Core has three basic goals for this project: ? Acquire data encompassing a broad range of behavioral domains (motor, learning, short-term memory, long-term memory, anxiety, depression, balance / coordination) over 4 time points (baseline, 24 hours postinjury, 72 hours post-injury, and 25-35 days post-injury). * Determine the effects of injury type (control vs. SAH vs. ICH vs. TBI), treatment (none vs. osteopontin vs. anti-PDGF vs. Cav-AP) and time (e.g., days 1 and 3, days 25-35) on the overall behavioral profile, as well as injury x treatment x time interactions. * Determine relationships between behavior and biomarkers from each model using data from the other Cores. Statistical modeling will allow us to determine which behavioral deficits tend to cluster together, suggesting common biological mechanisms. Data will be collected and analyzed in waves, which will allow for constant quality control and cost effecfiveness. For example, if it becomes clear that a particular test is ineffective in determining group difference, that test may be removed from the battery to save time and money.

Public Health Relevance

Behavior represents the final common pathway of neurological disorders. Identification of common and distinct features of brain injuries and treatments will help to determine the relationships between various behaviors and different brain areas, as well as the optimal treatment strategy and dosage.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
1P01NS082184-01A1
Application #
8661430
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
1
Fiscal Year
2014
Total Cost
$122,430
Indirect Cost
$34,502
Name
Loma Linda University
Department
Type
DUNS #
009656273
City
Loma Linda
State
CA
Country
United States
Zip Code
92350
Guo, Zongduo; Hu, Qin; Xu, Liang et al. (2016) Lipoxin A4 Reduces Inflammation Through Formyl Peptide Receptor 2/p38 MAPK Signaling Pathway in Subarachnoid Hemorrhage Rats. Stroke 47:490-7
Jullienne, Amandine; Obenaus, Andre; Ichkova, Aleksandra et al. (2016) Chronic cerebrovascular dysfunction after traumatic brain injury. J Neurosci Res 94:609-22
Yang, Peng; Manaenko, Anatol; Xu, Feng et al. (2016) Role of PDGF-D and PDGFR-β in neuroinflammation in experimental ICH mice model. Exp Neurol 283:157-64
Flores, Jerry J; Klebe, Damon; Rolland, William B et al. (2016) PPARγ-induced upregulation of CD36 enhances hematoma resolution and attenuates long-term neurological deficits after germinal matrix hemorrhage in neonatal rats. Neurobiol Dis 87:124-33
Wu, Jiang; Zhang, Yang; Yang, Peng et al. (2016) Recombinant Osteopontin Stabilizes Smooth Muscle Cell Phenotype via Integrin Receptor/Integrin-Linked Kinase/Rac-1 Pathway After Subarachnoid Hemorrhage in Rats. Stroke 47:1319-27
Yang, Peng; Wu, Jiang; Miao, Liyan et al. (2016) Platelet-Derived Growth Factor Receptor-β Regulates Vascular Smooth Muscle Cell Phenotypic Transformation and Neuroinflammation After Intracerebral Hemorrhage in Mice. Crit Care Med 44:e390-402
Yin, Cheng; Huang, Guang-Fu; Sun, Xiao-Chuan et al. (2016) Tozasertib attenuates neuronal apoptosis via DLK/JIP3/MA2K7/JNK pathway in early brain injury after SAH in rats. Neuropharmacology 108:316-23
Wang, Yuechun; Reis, Cesar; Applegate 2nd, Richard et al. (2015) Ischemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke. Exp Neurol 272:26-40
Chen, Yujie; Zhang, Yang; Tang, Junjia et al. (2015) Norrin protected blood-brain barrier via frizzled-4/β-catenin pathway after subarachnoid hemorrhage in rats. Stroke 46:529-36
Huang, Lei; Sherchan, Prativa; Wang, Yuechun et al. (2015) Phosphoinositide 3-Kinase Gamma Contributes to Neuroinflammation in a Rat Model of Surgical Brain Injury. J Neurosci 35:10390-401

Showing the most recent 10 out of 39 publications