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theses

Traumatic brain injury (TBI) causes severe cognitive disability or death, resulting from common occurrences as car accidents, falls, high-impact sport, violence, or explosive blasts. Statistical data indicate that approximately 2 million people are affected annually by TBI Traumatic brain injury (TBI) causes severe cognitive disability or death, resulting from common occurrences as car accidents, falls, high-impact sport, violence, or explosive blasts.
Statistical data indicate that approximately 2 million people are affected annually by TBI in the United States alone. Most of the time, the symptoms are evident immediately or soon after the impact. The injury results in various symptoms, such as seizures, cognitive disability, loss of memory, visual disturbances and other debilitating neurological problems. The patients require long rehabilitative treatments at a high cost for them and their families. At the moment, there are limited treatments available, and no effective cure for cognitive disability after TBI.
In this study, we investigated the potential role of the Reelin protein in neuroprotection and recovery after TBI. Reelin is a glycoprotein that regulates brain development during embryogenesis and synaptic plasticity during adult life. Reelin has been implicated in several developmental brain disorders, including epilepsy and schizophrenia, where its reduced expression may alter neuronal activity. A few studies also suggested that Reelin may play a role in the recovery after brain damage by stimulating adult neurogenesis, protecting tissue from cell death, and promoting tissue repair by restoring synaptic connectivity. In this work, we used the controlled cortical impact (CCI) technique to model TBI in the mouse brain and found that Reelin expression changes in response to the injury, especially in the hippocampus, an area of the brain that plays an important role in learning and memory. We also conducted in vitro experiments using mouse neuronal cultures and observed that exogenous Reelin protects neuronal cells from the toxicity induced by high doses of glutamate, an excitatory amino acid that increases rapidly in the extracellular space after brain injury. Based on these findings, we hypothesize that Reelin may be beneficial for neuroprotection and functional recovery after TBI. To further investigate recovery, we also performed preliminary behavioral studies in mice to establish whether CCI results in cognitive and motor deficits.
The long-term goal of this study is to firmly establish whether Reelin could be a new target for pharmacological intervention aimed at improving the quality of life for people affected by TBI.
 

ETD_10355

Ph.D.

Includes bibliographical references

doi:10.7282/t3-na7d-9e29

ETD doctoral

The author owns the copyright to this work.