Using preclinical rodent brain injury models, the Hubbard lab investigates mechanisms related to neurovascular and mitochondrial dysfunction in the brain as well as systemic manifestations of TBI. The goal is to understand the pathobiology of traumatic brain injury (TBI) and investigate therapeutics that can target critical mechanisms of injury to improve outcomes.
Blood-brain barrier disruption after repeated mild TBI
Blast-induced traumatic brain injury (TBI) is common in military settings and biomedical efforts to understand blast-induced TBI in order to treat neurological consequences are on-going. Exposure to even low-level blast (LLB) in military personnel results in adverse symptomatology and a unique form of mild brain injury, herein referred to as mild blast TBI (mbTBI). Neurovascular disruption is a hallmark of clinical presentations of blast TBI (bTBI) as well as that in preclinical blast models. Vascular deficits following blast exposure are well described in the literature and this mechanism is supported by many blast injury mechanisms, including direct cranial transmission of shear stress and hydrodynamic pulse through the circulatory system. In our research, we focus on vascular and blood–brain barrier (BBB) responses, including loss of tight junction proteins as well as microvascular pathology. Our goal is to target neurovascular dysfunction in order to improve behavioral outcomes after mbTBI.
Mitochondrial dysfunction after mild TBI
Mitochondria play a vital role in ATP production and maintenance of cellular calcium homeostasis, both which influence neurovascular coupling. Moderate-to-severe TBI disrupts mitochondrial function and facilitates excessive ROS production, leading to oxidative stress. Our research is dedicated to understand mitochondrial dysfunction in mild TBI, using novel mitochondrial approaches. Bioenergetic analysis was performed on mitochondria isolated from ventral cortex (containing entorhinal cortex). Significant depression of State III respiration
Neurovascular Metabolism after mild TBI
Mild TBI is not characterized by over neuronal death but rather cellular dysfunction. We are interested in how blood vessel metabolism is altered in response to brain injury. Vascular metabolism has been shown to direct vascular proliferation, recovery, and mechanisms of angiogenesis, which are all important after mTBI. Our group has optimized the isolation and purification of brain capillaries ex vivo to examine metabolic deficits after injury.
Coagulopathy after TBI
We have on-going collaboration with Dr. Jeremy Wood investigating coagulopathy and the increased risk of blood clotting after TBI. We find that blood-brain barrier disruption enables the release of small vesicles containing the coagulation initiator tissue factor, which propagates thrombin generation.