Using preclinical models of brain injury and blast exposure, the Hubbard Lab investigates mechanisms of neurovascular and mitochondrial dysfunction in the brain, as well as the neurological and systemic consequences of traumatic brain injury (TBI). Our goal is to define critical mechanisms that contribute to acute and chronic dysfunction following injury and develop therapeutic strategies that improve long-term outcomes.

Blood-Brain Barrier and Neurovascular Dysfunction After Blast TBI

Blast-induced traumatic brain injury (bTBI) is an important concern in military populations, where exposure to single or repeated blasts can contribute to persistent neurological symptoms. Even low-level blast exposures that do not produce overt brain injury may result in cumulative neurological and systemic effects. The neurovascular unit is particularly vulnerable to blast exposure. Our research investigates how blast and repeated mild TBI disrupt the cerebral microvasculature and blood-brain barrier (BBB), including alterations in endothelial function, tight junction integrity, and vascular-associated inflammatory responses. We are particularly interested in determining how early neurovascular dysfunction contributes to persistent neurological consequences and whether vascular-directed therapies can promote recovery following injury.

Mitochondrial Dysfunction and Neurovascular Metabolism After Blast TBI

Mitochondria are critical regulators of cellular energy production, calcium homeostasis, oxidative stress, and cell signaling. TBI can disrupt these processes, resulting in impaired bioenergetics, excessive reactive oxygen species production, and altered cellular metabolism. Our laboratory investigates mitochondrial dysfunction following mild and repeated TBI, with a particular focus on the brain microvasculature and neurovascular unit. We have developed approaches to isolate and purify intact brain capillaries to directly examine mitochondrial bioenergetics following injury. Current studies investigate how alterations in mitochondrial function, dynamics, transport, and cellular metabolism contribute to neurovascular dysfunction and whether targeting these processes can improve brain recovery.

Post-Traumatic Epilepsy and Hyperexcitability

Post-traumatic epilepsy (PTE) is a potentially devastating long-term consequence of TBI that can emerge months or years after the initial injury. Our laboratory investigates the mechanisms linking blast exposure and TBI to persistent neuronal hyperexcitability and epileptogenesis. Current studies examine the contributions of chronic neuroinflammation, neurovascular dysfunction, and altered cellular metabolism to the development of post-traumatic hyperexcitability and seizures. We use complementary behavioral, electrophysiological, and molecular approaches to identify mechanisms that may provide therapeutic targets for preventing PTE.

Intercellular Mitochondrial Transfer After TBI

In addition to functioning within individual cells, mitochondria can be transferred between cells and may serve as an endogenous mechanism for responding to cellular stress and injury. Our laboratory investigates intercellular mitochondrial transfer within the neurovascular unit following TBI, with particular interest in mitochondrial communication between astrocytes and the cerebral microvasculature. Our goal is to determine whether mitochondrial transfer contributes to vascular recovery following injury and whether this process can be therapeutically enhanced to restore cellular metabolism and neurovascular function.

Systemic Consequences of Blast Exposure

Blast exposure can affect organ systems beyond the brain. Our laboratory investigates systemic manifestations of blast injury and their relationship to neurological outcomes. Current projects examine auditory, visual and respiratory consequences of blast exposure, including mechanisms of blast-induced hearing dysfunction and the role of mitochondrial oxidative stress in tissue injury. These studies broaden our understanding of blast exposure as a multisystem injury and provide opportunities to develop therapies that protect both neurological and systemic function.