Dr. Costantino Iadecola's research focuses on the brain dysfunction and damage that underlie two of the most devastating brain diseases: stroke and dementia. Stroke, sometimes called "brain attack," is the second cause of death worldwide and the leading cause of brain damage. It is most often caused by a blockage of the blood vessels that supply the brain and leads to immediate paralysis, blindness, confusion, or language problems. Dementia, such as Alzheimer's disease, strikes an increasing number of elderly individuals resulting in severe memory problems, disorientation, confusion, and inability to care for oneself. The ultimate goal of Dr. Iadecola's research is to shed light on the causes of stroke and dementia, and to develop new therapies for these conditions. This research flows along several interconnected lines.
Hypertension and the brain. High blood pressure, or hypertension, is a major cause of stroke and dementia. Dr. Iadecola and his colleagues have discovered that cerebral blood vessels are uniquely susceptible to the deleterious effects of hypertension, and they are studying how such malfunction of blood vessels leads to stroke and Alzheimer's disease. Sleep apnea and aging, conditions well known to cause stroke and dementia, also alter brain blood vessels in a similar fashion. They have identified several therapeutic targets that would help protect the brain and its vessels from the damaging effects of hypertension.
Why does the brain die after stroke? Dr. Iadecola's lab group is investigating the cellular and molecular alterations in the brain caused by blockage of the blood supply. They found that stroke activates certain cells of the immune system and produces brain inflammation. Blocking the action of these cells improves the brain damage caused by the stroke. They are now looking at what triggers inflammation and finding ways to stop it to salvage the brain. On the other hand, they also discovered that a certain type of immune cells protect the brain after stroke. This is a new and exciting area of investigation that may lead to developing new cell therapies for stroke.
Alzheimer's disease and stroke. Once considered mutually exclusive, these two highly prevalent brain diseases are now known to have much in common. The work of Dr. Iadecola and his lab group have revealed that Alzheimer's disease damages blood vessels in a manner similar to hypertension and stroke. Improving the performance of the blood vessels of the brain also improves the brain alterations produced by Alzheimer's disease. They have identified a "receptor" in brain vessels that binds chemicals accumulating in Alzheimer's disease (amyloid-β peptides) resulting in their damage and are developing ways to block this receptor to protect the brain from the damaging effects of amyloid-β.
Bright and dark sides of brain plasticity. The remarkable ability to learn and adapt to a changing environment, known as neuroplasticity, is a defining characteristic of the brain. Neuroplasticity is mediated by subtle changes in the connections through which neurons communicate with each other and can protect the brain from the damage associated with stroke and dementia. However, neuroplasticity also has a dark side. Dr. Iadecola and his colleagues have discovered that the synaptic changes that underlie learning and memory are similar to those induced by hypertension, drug addiction, and sleep apnea. They are developing ways to harness the "good" side of neuroplasticity to protect the brain from the damaging effects of stroke and dementia.