Endocrine disruption in brain injury and mitochondria-targeted protective mechanisms


Patients with traumatic brain injury (TBI) experience a severe endocrine disruption, which is characterized by altered hormone levels in both the blood and brain. Our goal is to further investigate how these changes impact its pathological mechanisms. TBI is recognized as a high risk factor for Alzheimer's disease and dementia. To simulate TBI in the lab, we utilize two models:


An in vitro model where we induce mechanical damage to cells along with metabolic dysfunction, which deprives cells of nutrients. The mechanical damage resulting from trauma leads to the massive death of neurons and glial cells, followed by metabolic injury, which is a consequence of the destruction of cerebral vessels and arteries. This hinders the normal flow of glucose and nutrients to the surrounding tissues, both of which are hallmarks of traumatic brain injury. Our team was the first to develop this new in vitro model, and it remains our primary model for use in our studies (Torrente et al., 2014; Baez et al., 2019a, 2019b, 2018a, 2018b)


In vitro traumatic brain injury model.


... and a penetrating brain injury to model brain trauma in animals. In this model, a needle is inserted into the murine brain and moved anteroposteriorly to affect both the hippocampus and the cerebral cortex, thereby impairing motor, learning, and cognitive behavior.


In vivo traumatic brain injury model.

Dysregulation of lipid metabolism and neuroimmune response following brain damage


Brain damage causes profound impairment of lipid metabolism in the brain. The mechanical damage itself provokes membrane disruption, leading to an aberrant release of lipids and cholesterol from subcellular compartments. More importantly, mitochondrial dysfunction is a hallmark of brain pathology, affecting the way cells metabolize lipids in this organelle. We are keen on thoroughly understanding how this leads to chronic inflammation and a strong neuroimmune response.


Accumulation of lipids in the brain is a chronic feature in brain injury and to better understand how this affects cell fate we use in silico and in vitro approaches to simulate this pathological alteration.