Chenghua Gu, PhD

The brain, which represents 2% of the body mass but consumes 20% of the body energy at rest, is highly dependent on a continuous supply of oxygen and nutrients from the blood stream. To accommodate this high demand, blood vessels  in the brain differ from the rest of the body. First, brain blood vessels have a gate, called the Blood-Brain Barrier (BBB), that permits vital nutrients to pass into the brain, but blocks the entry of harmful viruses and bacteria. While the selectivity of the BBB is beneficial to the brain, it comes at a cost: the gate is so selective that it can block the entry of therapeutic agents. Moreover, a leaky, non-selective BBB is one of the earliest features in many neurological diseases. Thus, a major challenge is to identify ways of manipulating the BBB to transiently open the barrier to deliver drugs, or to tighten the barrier to delay progression of neurodegeneration.

Second, blood vessels in the brain are functionally coupled to neural activity, such that neural activity rapidly increases local blood flow to meet moment-to-moment changes in regional brain energy demand. Neurovascular coupling is also the basis for functional brain imaging in human. We are exploring how this process influences neural function and behavior.

Third, the brain vasculature is the first line of contact between the brain and the periphery as systemic circulation contains factors released from all organs. So, any substance that affects the brain must first talk to brain endothelial cells. For example, peripheral inflammation profoundly influences brain health. We are investigating how  brain endothelial cells transmit peripheral immune signals to the brain.

How the brain vasculature carries out these diverse and critical functions by interacting with the systemic and brain factors to control brain’s own environment and energy is an important and largely uncharted research area.

The goal of our research is to understand the molecular and cellular mechanisms underlying BBB function and neurovascular coupling. Achieving our goals could have a big impact on therapeutics and change how neurological diseases are treated.