Do neurodegeneration and dementia result from failure of reactive astrocytes to regulate blood flow?

An estimated 1.7 to 3.8 million people in the US incur a Traumatic Brain Injury (TBI) each year. The vast majority of these cases are mild (previously called "concussive") and patients might not seek medical attention. Yet, mild TBI/ concussion can cause problems affecting cognition, emotion and behavior. While these symptoms improve within the first few months for most people, some develop persistent post-TBI symptoms including depression, anxiety and cognitive impairment. Thus, mTBI is a major public health concern.

Currently, we do not have a good understanding of risk factors and mechanisms inducing lasting changes in some patients but not others. However, recently it has become apparent that individuals who suffered repeated mTBI can face longer recovery times, greater symptom severity, and earlier onset of age-related memory deficits and dementia. These symptoms occur in the absence of readily detectable primary tissue damage on CT scans. However, mTBI patients can present with reduced cerebral blood flow (CBF).

Massive reduction of blood flow, for instance in stroke, causes impaired cognitive function within seconds and, if it persists, can result in irreparable damage of brain tissue. After TBI, a decline in blood flow is strongly associated with poorer clinical outcome although this decrease typically lies above the threshold level associated with ischemic brain injury.

Both the sufficient blood supply of active brain regions and blood flow at the resting state are assured by the neurovascular unit (NVU), a functional entity consisting of neural and vascular cells. Astrocytes, glial cells in the brain, are ideally positioned within the NVU to modulate the regulation of blood flow. To study if astrocyte function within the neurovascular unit is impaired after mild TBI/ concussion, if damage to the neurovascular unit affects blood flow and secondarily neuronal function, we use imaging techniques combined with behavioral assays and electrophysiology.