Our Research
Diabetes
Glucose is the primary source of energy for the brain. However the brain is particularly sensitive to excessive levels of circulating sugar. Unlike other organs, the brain is unable to stop high levels of sugars rushing in, thus the brain is especially vulnerable to diabetes. As diabetes continues to grow as a public health issue, understanding how diabetes alters the brian is crucial. Type 1 diabetics (T1DM) are at significantly greater risk for developing cognitive impairment and dementia, and T1DM is a major risk factor for stroke, and significantly impairs functional recovery. Unfortunately, no cure exists as insulin cannot completely prevent or mitigate the impact of these neurological complications.
Recent studies from our lab have discovered that cerebral capillaries are prone to stalling/clogging. Under healthy conditions, this occurs in about 0.5-2% of capillaries at any given time, which are usually short-lived (~ seconds to minutes). However, under pathological conditions such as stroke or Alzheimer’s disease, the incidence and duration of these stalls increases dramatically which can negatively affect cognitive function.
Given the fact that diabetes is well known to disrupt vascular function and is associated with chronic inflammation, there is a pressing need to better understand the etiopathology of diabetes related neurological complications, which will enable the development of rational and effective therapeutics. The lab studies short and long term changes to cerebral blood flow and brain function in diabetic mice using functional imaging, molecular assays and behavioral tests.
Stroke
Stroke is a cerebrovascular injury that results in massive cell death in the ischemic core as well as chronic dysfunction in surviving brain regions. The long-term impact of stroke varies considerably in the severity and nature of functional impairment. However, few stroke patients exhibit full recovery, leaving a large population with chronic disability. Currently, treatment options for restoring function are mostly limited to physical therapy, which can be beneficial to some patients, but as a stand-alone intervention rarely yields full restitution of sensory and motor abilities.
A missing piece in our understanding of stroke recovery is a complete understanding of how local and distant, but connected, neuronal circuits rewire to provide some, albeit incomplete, recovery of lost functions. It is hoped that a full accounting of all the circuits impacted by stroke, and an understanding of how they can adapt, will lead to better therapies that specifically target functional recovery.
To unravel the widespread effects of ischemic injury the Brown lab images neuronal activity in awake behaving mice through genetically encoded fluorescent reports in near and far cortical regions after injury.
Neuroinflammation
Historically the central nervous system was considered to be an immune privileged environment, however this all changed with the discovery of a resident immune cell in the CNS, microglia. As we now know that neural inflammation is a major factor in many diseases of the brian, there is a great need to discover how these cells behave and react to injury. New lines of genetically encoded fluorescent reporters in microglia allow us to image the dynamism of these cells in the healthy, injured and/or diseased cortex.
The Brown lab is particularly interested in how sex differences affect microglia behavior. Many neuroinflammatory diseases such as Multiple Sclerosis, affect women far more often than men. Surprisingly the Brown Lab recently discovered that a strong sex difference is also present in the behavior of microglia in the rodent cortex. This discovery has opened a new direction of research in the lab, understanding the effects of sex hormones and other sex differences on the function of the brain’s resident immune cells.
Our Work
FITC-dye vessels and tdTomato labelled microglia
Click on image to enlarge.