Suffering from a heart attack or heart disease or undergoing cardiac surgical interventions puts people at an increased risk for cognitive deficits such as Alzheimer’s disease and dementia. Previous research has determined a connection between mental stressors and heart disease as well as heart damage. Similar to a gut-brain connection, these studies show evidence of a distinct cellular connection between the heart and the brain. In an article published in the Journal of Nuclear Medicine in 2019, James Thackeray describes patterns of inflammation to brain tissue following heart damage caused by myocardial infarction in rodent subjects. The results further support the theory of a heart-brain axis and describe additional mechanistic properties that may contribute to the connection.

Background

A connection between the cardiac and nervous systems has been described in research dating back to the 1900’s. Syncopal episodes and even death have both been reported as results of extreme emotional episodes and periods of intense stress.¹ Most recently, diseases such as Takotsubo cardiomyopathy and chronic hypertension have been shown to be caused as a direct result of consistent psychological stress.² One of the most common cardiovascular diseases—congestive heart failure (CHF)—affects more than 64 million people across the world and recent studies have shown that nearly 80% of those diagnosed with CHF experience cognitive deficits.³ To explore the effects of common heart conditions, this study examined the cellular neurological effects of heart attacks in mice. A heart attack occurs when the artery that supplies the heat with oxygenated blood—the coronary artery—becomes blocked. Fatty deposits build up over time in the arteries of the heart forming plaques along the artery wall. When a plaque ruptures and dislodges from the artery wall, a blood clot can form and block the artery causing the heart attack.⁴ When the coronary artery is blocked, red blood cells carrying oxygen molecule can no longer reach the muscle tissues of the heart which causes cell death to the affected areas and the secretion of chemical signals that results in the recruitment of inflammatory cells.⁴ There are many cognitive deficits that have been reported following cardiac damage and onset of cardiac disease. As a result, Neurocardiology is growing specialty that explores the effects of cardiac injury on the brain, and the effects of brain injury on the heart.⁵

Methods

In this study, the coronary arteries of mouse subjects were occluded to induce ischemia that mimics that which results from spontaneous myocardial infarction. At 1 week, 4 weeks, and 8 weeks post artery occlusion, neuroinflammation and cardiac inflammation were imaged using positron emission tomography (PET) scans. PET scans quantified presence of TSPO, a translocator protein found on the outer membrane of mitochondria. This protein is widely used as a marker of neuroinflammation as it is upregulated by the activation of microglia in numerous neuronal pathologies.⁶ TSPO has also been implicated in an overlap between activated microglia and pro-inflammatory cytokines.⁷ In addition to acting as a marker for neuroinflammation, TSPO is a useful marker in studies involving cardiac systems as it is a marker of macrophages which have been shown to be abundant in infarct areas following MI.⁸ To show cognitive consequences following cardiac ischemic injury, immunofluorescence staining was performed to test for colocalization of TSPO, and CD68+ macrophages.

Results

This study found that TSPO PET signals were increased in the infarct area at 1 week post artery occlusion. The increased signaling was colocalized to CD68+ macrophages. At 4 weeks after myocardial infarction, the TSPO PET signals returned to baseline levels when examining the areas where infarct occurred. After this intermediate decline, signals were reelevated 8 weeks post MI and were localized to the remote myocardium.⁹ PET scans were performed on the brain of the subjects concurrently with cardiac imaging. It was found that neuroinflammation followed a similar pattern with an increase in TSPO signaling that colocalized to CD68+ microglia in the cortex at the 1week mark, a temporary return to baseline levels, and re-elevation at 8 weeks.

Neuroinflammation is a general response to alterations to brain homeostasis. As a result, the inflammation caused as a result of heart attack operates via a mechanism that has yet to be identified. This research has potential implications in dementia and Alzheimer’s research in patients with histories of congestive heart failure and myocardial infarction resulting in cardiac ischemic injury. While TSPO functions as an inciteful marker for cardiac and neuroinflammation, new tracers are needed that are able to mark specific interconnections between the heart and brain. This preliminary study suggests the involvement of the frontal cortex in cardiac ischemia-associated neuro deficits though larger-scale studies are still needed.

[+] References

[+] Other Work By Ella Cary