Temporal Profile and Severity Correlation of a Panel of Rat Spinal Cord Injury Protein Biomarkers.

In the USA, there are approximately 12,000 new cases of spinal cord injury (SCI) each year and some 1.2 million people living with paralysis due to SCI. Seven percent of them are paralyzed due to an accident or injury occurring while serving in the military. Here, we report a systematic study on protein biomarker candidates in a rat SCI model with either moderate or severe injury. Tissue, cerebrospinal fluid (CSF), and serum samples were obtained at 4 h, 24 h, and 7 days post-injury. The candidate biomarkers included axonal injury markers αII-spectrin breakdown products (SBDP150/145/120), neuronal cell body injury marker ubiquitin C-terminal hydrolase-L1 (UCH-L1), astrogliosis/astroglial injury markers S100 calcium-binding protein-ß (S100ß), glial fibrillary acidic protein (GFAP) and GFAP breakdown products (GBDPs), demyelination marker myelin basic protein (MBP), axonal injury marker phosphorylated neurofilament-H (pNF-H), and neuroinflammation marker interleukin-6 (IL-6). SBDP150/145, UCH-L1, GFAP, and S100ß were found as acute biomarkers with significantly elevated levels within 24 h. GBDP44, GBDP38, and pNF-H are acute and subacute biomarkers that were found to have increased at 4 h, 24 h, and 7 days. MBP and SBDP120 were considered subacute biomarkers which were only detectable at 7 days post-injury. These results not only allow us to gain important insight into the patho-mechanisms of SCI but also showcase the possibility of using some of the protein biomarkers to track injury severity and disease progression and resolution. These biomarkers can potentially serve as tools that assist therapy development and clinical trials.

Temporal MRI characterization, neurobiochemical and neurobehavioral changes in a mouse repetitive concussive head injury model.

Single and repeated sports-related mild traumatic brain injury (mTBI), also referred to as concussion, can result in chronic post-concussive syndrome (PCS), neuropsychological and cognitive deficits, or chronic traumatic encephalopathy (CTE). However PCS is often difficult to diagnose using routine clinical, neuroimaging or laboratory evaluations, while CTE currently only can be definitively diagnosed postmortem. We sought to develop an animal model to simulate human repetitive concussive head injury for systematic study. In this study, mice received single or multiple head impacts by a stereotaxic impact device with a custom-made rubber tip-fitted impactor. Dynamic changes in MRI, neurobiochemical markers (Tau hyperphosphorylation and glia activation in brain tissues) and neurobehavioral functions such as anxiety, depression, motor function and cognitive function at various acute/subacute (1-7 day post-injury) and chronic (14-60 days post-injury) time points were examined. To explore the potential biomarkers of rCHI, serum levels of total Tau (T-Tau) and phosphorylated Tau (P-Tau) were also monitored at various time points. Our results show temporal dynamics of MRI consistent with structural perturbation in the acute phase and neurobiochemical changes (P-Tau and GFAP induction) in the subacute and chronic phase as well as development of chronic neurobehavioral changes, which resemble those observed in mTBI patients.