Oligodendrocytes, the myelinating cells of central nervous system, have extraordinary demands for oxygen, nutrients, and metabolic substrates associated with production of myelin protein and proteolipid as well as axonotrophic support. This suggests that establishment of cerebrovascular network, which ensures adequate blood supply and oxygenation, as an important regulatory step in the process of white matter myelination. White matter dysfunction and myelination deficits are therefore increasingly implicated in both neonatal brain injuries and neurodevelopmental disorders with a component of vascular pathology or genetic lesions affecting cerebral vascular endothelium or cerebral blood flow.

 

The Chavali Lab is interested in understanding the cellular and molecular mechanisms regulating oligodendroglial and cerebral vascular development and applying the insights gained from these studies to better understand white matter injury in premature birth, congenital heart disease (CHD), multiple sclerosis (MS) and leukodystrophy. ​

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To mimic the pathophysiology of neonatal brain injuries, we use various hypoxia models and also tissue specific knockout model of CHD. To model the white matter pathology seen in MS, we use both acute and chronic demyelination injuries as well as a genetically induced oligodendrocyte cell death model. We also use Plp1, ABCD1 and SLC2A1 mutants, which model various leukodystrophies and metabolic disorders. Using these models we are trying to address: 

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• How do altered cerebral blood flow and/or cerebral oxygen delivery affect myelin synthesis and white matter function?

• What is the function of the oligodendroglial-endothelial cell interactions during myelination and remyelination?

• How does disruption in oligodendroglial precursor development in neonatal brain injury affect neuronal circuitry?