The concept of the “neurovascular” unit (NVU) has recently emerged from the understanding that cells such as neurons, astrocytes, pericytes and vascular cells constitute a functional unit whose primary purpose is to maintain the chemical composition of the brain microenvironment by regulating cerebral blood flow (CBF), molecular transport across the blood brain barrier (BBB) and neurotransmitter homeostasis. Furthermore, astrocytes, perivascular microglia and bone marrow derived macrophages interact with each other to orchestrate coordinated neuroinflammatory responses. In addition to involving direct physical contact, these interactions occur through positive and negative feedback mechanisms. These complex mechanisms are likely to have important effects on microvascular function and integrity which in turn may be critical for the stability and plasticity of neuronal connections. Thus, the emerging view is that NVU dysregulation is a feature not only of cerebrovascular pathologies, such as stroke, but also of neurodegenerative conditions, such as Alzheimer's disease. Our laboratory is interested in a range of issues related to the development, physiology and pathology of the NVU. We also devise new approaches to study at high spatio-temporal resolution, cellular interactions within the NVU, using optical imaging techniques such as two photon microscopy, genetic tools and experimental disease models

RESEARCH INTERESTS:

a) In vivo imaging of the neurovascular unit: To study cell-cell interactions in the neurovascular unit we develop methods using two-photon microscopy (TPM) to repeatedly image individual neurons, dendritic spines, microglia, astrocytes and blood vessels over periods of up to months in the brain of living mice

b) Vascular and metabolic mechanisms of neuronal circuit disruption : we are interested in understanding how neurons and astrocytes adapt to metabolic challenges such as chronic focal and global hypoperfusion and mild hypoxia

c) Cerebral microvascular development and pathology: we are interested in learning about the dynamics of developing microvessels and their interaction with astrocytes an perycytes. We also study how vessels respond to microocclusion and how aging affects these responses

d) Role of neuroinflammation in neurodegeneration: we are actively studying the interactions between microglia, neurons and amyloid plaques in Alzheimer's disease to determine the potential role of microglia in plaque formation or removal as well as in secondary neuronal injury